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  • Computational Methods, Genomics  (67)
  • Cooperatives  (41)
  • Oxford University Press  (108)
  • International Union of Crystallography (IUCr)
  • 2010-2014  (108)
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  • Oxford University Press  (108)
  • International Union of Crystallography (IUCr)
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  • 1
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    Graph-based modeling of tandem repeats improves global multiple sequence alignment (2013)
    Oxford University Press
    Details
    Publikationsdatum: 2013-09-26
    Beschreibung: Tandem repeats (TRs) are often present in proteins with crucial functions, responsible for resistance, pathogenicity and associated with infectious or neurodegenerative diseases. This motivates numerous studies of TRs and their evolution, requiring accurate multiple sequence alignment. TRs may be lost or inserted at any position of a TR region by replication slippage or recombination, but current methods assume fixed unit boundaries, and yet are of high complexity. We present a new global graph-based alignment method that does not restrict TR unit indels by unit boundaries. TR indels are modeled separately and penalized using the phylogeny-aware alignment algorithm. This ensures enhanced accuracy of reconstructed alignments, disentangling TRs and measuring indel events and rates in a biologically meaningful way. Our method detects not only duplication events but also all changes in TR regions owing to recombination, strand slippage and other events inserting or deleting TR units. We evaluate our method by simulation incorporating TR evolution, by either sampling TRs from a profile hidden Markov model or by mimicking strand slippage with duplications. The new method is illustrated on a family of type III effectors, a pathogenicity determinant in agriculturally important bacteria Ralstonia solanacearum. We show that TR indel rate variation contributes to the diversification of this protein family.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 2
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    Meander: visually exploring the structural variome using space-filling curves (2013)
    Oxford University Press
    Details
    Publikationsdatum: 2013-06-08
    Beschreibung: The introduction of next generation sequencing methods in genome studies has made it possible to shift research from a gene-centric approach to a genome wide view. Although methods and tools to detect single nucleotide polymorphisms are becoming more mature, methods to identify and visualize structural variation (SV) are still in their infancy. Most genome browsers can only compare a given sequence to a reference genome; therefore, direct comparison of multiple individuals still remains a challenge. Therefore, the implementation of efficient approaches to explore and visualize SVs and directly compare two or more individuals is desirable. In this article, we present a visualization approach that uses space-filling Hilbert curves to explore SVs based on both read-depth and pair-end information. An interactive open-source Java application, called Meander , implements the proposed methodology, and its functionality is demonstrated using two cases. With Meander , users can explore variations at different levels of resolution and simultaneously compare up to four different individuals against a common reference. The application was developed using Java version 1.6 and Processing.org and can be run on any platform. It can be found at http://homes.esat.kuleuven.be/~bioiuser/meander .
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 3
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    FOAM (Functional Ontology Assignments for Metagenomes): a Hidden Markov Model (HMM) database with environmental focus (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-11-07
    Beschreibung: A new functional gene database, FOAM (Functional Ontology Assignments for Metagenomes), was developed to screen environmental metagenomic sequence datasets. FOAM provides a new functional ontology dedicated to classify gene functions relevant to environmental microorganisms based on Hidden Markov Models (HMMs). Sets of aligned protein sequences (i.e. ‘profiles’) were tailored to a large group of target KEGG Orthologs (KOs) from which HMMs were trained. The alignments were checked and curated to make them specific to the targeted KO. Within this process, sequence profiles were enriched with the most abundant sequences available to maximize the yield of accurate classifier models. An associated functional ontology was built to describe the functional groups and hierarchy. FOAM allows the user to select the target search space before HMM-based comparison steps and to easily organize the results into different functional categories and subcategories. FOAM is publicly available at http://portal.nersc.gov/project/m1317/FOAM/ .
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 4
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    svaseq: removing batch effects and other unwanted noise from sequencing data (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-11-28
    Beschreibung: It is now known that unwanted noise and unmodeled artifacts such as batch effects can dramatically reduce the accuracy of statistical inference in genomic experiments. These sources of noise must be modeled and removed to accurately measure biological variability and to obtain correct statistical inference when performing high-throughput genomic analysis. We introduced surrogate variable analysis (sva) for estimating these artifacts by (i) identifying the part of the genomic data only affected by artifacts and (ii) estimating the artifacts with principal components or singular vectors of the subset of the data matrix. The resulting estimates of artifacts can be used in subsequent analyses as adjustment factors to correct analyses. Here I describe a version of the sva approach specifically created for count data or FPKMs from sequencing experiments based on appropriate data transformation. I also describe the addition of supervised sva (ssva) for using control probes to identify the part of the genomic data only affected by artifacts. I present a comparison between these versions of sva and other methods for batch effect estimation on simulated data, real count-based data and FPKM-based data. These updates are available through the sva Bioconductor package and I have made fully reproducible analysis using these methods available from: https://github.com/jtleek/svaseq .
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 5
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    Insyght: navigating amongst abundant homologues, syntenies and gene functional annotations in bacteria, it's that symbol! (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-11-28
    Beschreibung: High-throughput techniques have considerably increased the potential of comparative genomics whilst simultaneously posing many new challenges. One of those challenges involves efficiently mining the large amount of data produced and exploring the landscape of both conserved and idiosyncratic genomic regions across multiple genomes. Domains of application of these analyses are diverse: identification of evolutionary events, inference of gene functions, detection of niche-specific genes or phylogenetic profiling. Insyght is a comparative genomic visualization tool that combines three complementary displays: (i) a table for thoroughly browsing amongst homologues, (ii) a comparator of orthologue functional annotations and (iii) a genomic organization view designed to improve the legibility of rearrangements and distinctive loci. The latter display combines symbolic and proportional graphical paradigms. Synchronized navigation across multiple species and interoperability between the views are core features of Insyght. A gene filter mechanism is provided that helps the user to build a biologically relevant gene set according to multiple criteria such as presence/absence of homologues and/or various annotations. We illustrate the use of Insyght with scenarios. Currently, only Bacteria and Archaea are supported. A public instance is available at http://genome.jouy.inra.fr/Insyght . The tool is freely downloadable for private data set analysis.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 6
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    iPro54-PseKNC: a sequence-based predictor for identifying sigma-54 promoters in prokaryote with pseudo k-tuple nucleotide composition (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-11-28
    Beschreibung: The 54 promoters are unique in prokaryotic genome and responsible for transcripting carbon and nitrogen-related genes. With the avalanche of genome sequences generated in the postgenomic age, it is highly desired to develop automated methods for rapidly and effectively identifying the 54 promoters. Here, a predictor called ‘ iPro54-PseKNC ’ was developed. In the predictor, the samples of DNA sequences were formulated by a novel feature vector called ‘pseudo k -tuple nucleotide composition’, which was further optimized by the incremental feature selection procedure. The performance of iPro54-PseKNC was examined by the rigorous jackknife cross-validation tests on a stringent benchmark data set. As a user-friendly web-server, iPro54-PseKNC is freely accessible at http://lin.uestc.edu.cn/server/iPro54-PseKNC . For the convenience of the vast majority of experimental scientists, a step-by-step protocol guide was provided on how to use the web-server to get the desired results without the need to follow the complicated mathematics that were presented in this paper just for its integrity. Meanwhile, we also discovered through an in-depth statistical analysis that the distribution of distances between the transcription start sites and the translation initiation sites were governed by the gamma distribution, which may provide a fundamental physical principle for studying the 54 promoters.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 7
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    Binding site discovery from nucleic acid sequences by discriminative learning of hidden Markov models (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-11-28
    Beschreibung: We present a discriminative learning method for pattern discovery of binding sites in nucleic acid sequences based on hidden Markov models. Sets of positive and negative example sequences are mined for sequence motifs whose occurrence frequency varies between the sets. The method offers several objective functions, but we concentrate on mutual information of condition and motif occurrence. We perform a systematic comparison of our method and numerous published motif-finding tools. Our method achieves the highest motif discovery performance, while being faster than most published methods. We present case studies of data from various technologies, including ChIP-Seq, RIP-Chip and PAR-CLIP, of embryonic stem cell transcription factors and of RNA-binding proteins, demonstrating practicality and utility of the method. For the alternative splicing factor RBM10, our analysis finds motifs known to be splicing-relevant. The motif discovery method is implemented in the free software package Discrover. It is applicable to genome- and transcriptome-scale data, makes use of available repeat experiments and aside from binary contrasts also more complex data configurations can be utilized.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 8
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    Product quality in the agri-food chain: do cooperatives offer high-quality wine? (2012)
    Oxford University Press
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    Publikationsdatum: 2012-12-28
    Beschreibung: We investigate the impact of decentralised decision-making on product quality. Comparing a cooperative and an investor-owned firm suggests that members of the cooperative have an incentive to produce too much and to free-ride on quality. Whether or not cooperatives deliver higher quality products depends on the way in which the quality of the final product is determined from the quality levels of the inputs delivered (quality aggregation) as well as the number of members of the cooperative. Empirical evidence on the Austrian wine market suggests that wines produced by cooperatives tend to be of significantly lower quality, ceteris paribus .
    Schlagwort(e): D22 - Firm Behavior: Empirical Analysis, D23 - Organizational Behavior ; Transaction Costs ; Property Rights, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 0165-1587
    Digitale ISSN: 1464-3618
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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  • 9
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    Spatial localization of co-regulated genes exceeds genomic gene clustering in the Saccharomyces cerevisiae genome (2013)
    Oxford University Press
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    Publikationsdatum: 2013-02-20
    Beschreibung: While it has been long recognized that genes are not randomly positioned along the genome, the degree to which its 3D structure influences the arrangement of genes has remained elusive. In particular, several lines of evidence suggest that actively transcribed genes are spatially co-localized, forming transcription factories; however, a generalized systematic test has hitherto not been described. Here we reveal transcription factories using a rigorous definition of genomic structure based on Saccharomyces cerevisiae chromosome conformation capture data, coupled with an experimental design controlling for the primary gene order. We develop a data-driven method for the interpolation and the embedding of such datasets and introduce statistics that enable the comparison of the spatial and genomic densities of genes. Combining these, we report evidence that co-regulated genes are clustered in space, beyond their observed clustering in the context of gene order along the genome and show this phenomenon is significant for 64 out of 117 transcription factors. Furthermore, we show that those transcription factors with high spatially co-localized targets are expressed higher than those whose targets are not spatially clustered. Collectively, our results support the notion that, at a given time, the physical density of genes is intimately related to regulatory activity.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 10
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    Farmers' satisfaction and intention to continue membership in agricultural marketing co-operatives: neoclassical versus transaction cost considerations (2013)
    Oxford University Press
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    Publikationsdatum: 2013-02-26
    Beschreibung: The survival of agricultural marketing co-operatives depends on their capability of satisfying and maintaining their base of farmer members. Hypotheses regarding these two success factors are developed in neoclassical economics and transaction cost economics. They are tested with a survey of 321 members of marketing co-operatives specialising in fresh fruits and vegetables. Our results show support for both perspectives. Price paid to farmers is important for their satisfaction with the co-operative. Farmers' perceptions of transaction costs are even more important.
    Schlagwort(e): D22 - Firm Behavior: Empirical Analysis, D23 - Organizational Behavior ; Transaction Costs ; Property Rights, P13 - Cooperative Enterprises, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 0165-1587
    Digitale ISSN: 1464-3618
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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  • 11
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    Combining discrete and continuous mixing distributions to identify niche markets for food (2013)
    Oxford University Press
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    Publikationsdatum: 2013-02-26
    Beschreibung: This paper explores the demand and willingness to pay (WTP) for value-added services to chicken. Since the demand for such services are likely to be highly segmented and often applies only to a market niche, models based on assumptions of homogeneity among consumers are likely to be inappropriate. For this reason, this paper combines discrete and continuous mixing distributions to concurrently identify the size of the niche market and the heterogeneity among consumers within the market niche. Failing to account for the niche market nature of value-added services is shown to have implications for predictions of WTP, demand and total revenue.
    Schlagwort(e): C25 - Discrete Regression and Qualitative Choice Models, D12 - Consumer Economics: Empirical Analysis, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 0165-1587
    Digitale ISSN: 1464-3618
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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  • 12
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    PanOCT: automated clustering of orthologs using conserved gene neighborhood for pan-genomic analysis of bacterial strains and closely related species (2012)
    Oxford University Press
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    Publikationsdatum: 2012-12-14
    Beschreibung: Pan-genome ortholog clustering tool ( PanOCT ) is a tool for pan-genomic analysis of closely related prokaryotic species or strains. PanOCT uses conserved gene neighborhood information to separate recently diverged paralogs into orthologous clusters where homology-only clustering methods cannot. The results from PanOCT and three commonly used graph-based ortholog-finding programs were compared using a set of four publicly available strains of the same bacterial species. All four methods agreed on ~70% of the clusters and ~86% of the proteins. The clusters that did not agree were inspected for evidence of correctness resulting in 85 high-confidence manually curated clusters that were used to compare all four methods.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 13
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    A novel ab initio identification system of transcriptional regulation motifs in genome DNA sequences based on direct comparison scheme of signal/noise distributions (2012)
    Oxford University Press
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    Publikationsdatum: 2012-10-10
    Beschreibung: A novel ab initio parameter-tuning-free system to identify transcriptional factor (TF) binding motifs (TFBMs) in genome DNA sequences was developed. It is based on the comparison of two types of frequency distributions with respect to the TFBM candidates in the target DNA sequences and the non-candidates in the background sequence, with the latter generated by utilizing the intergenic sequences. For benchmark tests, we used DNA sequence datasets extracted by ChIP-on-chip and ChIP-seq techniques and identified 65 yeast and four mammalian TFBMs, with the latter including gaps. The accuracy of our system was compared with those of other available programs (i.e. MEME, Weeder, BioProspector, MDscan and DME) and was the best among them, even without tuning of the parameter set for each TFBM and pre-treatment/editing of the target DNA sequences. Moreover, with respect to some TFs for which the identified motifs are inconsistent with those in the references, our results were revealed to be correct, by comparing them with other existing experimental data. Thus, our identification system does not need any other biological information except for gene positions, and is also expected to be applicable to genome DNA sequences to identify unknown TFBMs as well as known ones.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 14
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    Identification of new microRNA-regulated genes by conserved targeting in plant species (2012)
    Oxford University Press
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    Publikationsdatum: 2012-10-10
    Beschreibung: MicroRNAs (miRNAs) are major regulators of gene expression in multicellular organisms. They recognize their targets by sequence complementarity and guide them to cleavage or translational arrest. It is generally accepted that plant miRNAs have extensive complementarity to their targets and their prediction usually relies on the use of empirical parameters deduced from known miRNA–target interactions. Here, we developed a strategy to identify miRNA targets which is mainly based on the conservation of the potential regulation in different species. We applied the approach to expressed sequence tags datasets from angiosperms. Using this strategy, we predicted many new interactions and experimentally validated previously unknown miRNA targets in Arabidopsis thaliana . Newly identified targets that are broadly conserved include auxin regulators, transcription factors and transporters. Some of them might participate in the same pathways as the targets known before, suggesting that some miRNAs might control different aspects of a biological process. Furthermore, this approach can be used to identify targets present in a specific group of species, and, as a proof of principle, we analyzed Solanaceae -specific targets. The presented strategy can be used alone or in combination with other approaches to find miRNA targets in plants.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 15
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    Use of ChIP-Seq data for the design of a multiple promoter-alignment method (2012)
    Oxford University Press
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    Publikationsdatum: 2012-04-15
    Beschreibung: We address the challenge of regulatory sequence alignment with a new method, Pro-Coffee, a multiple aligner specifically designed for homologous promoter regions. Pro-Coffee uses a dinucleotide substitution matrix estimated on alignments of functional binding sites from TRANSFAC. We designed a validation framework using several thousand families of orthologous promoters. This dataset was used to evaluate the accuracy for predicting true human orthologs among their paralogs. We found that whereas other methods achieve on average 73.5% accuracy, and 77.6% when trained on that same dataset, the figure goes up to 80.4% for Pro-Coffee. We then applied a novel validation procedure based on multi-species ChIP-seq data. Trained and untrained methods were tested for their capacity to correctly align experimentally detected binding sites. Whereas the average number of correctly aligned sites for two transcription factors is 284 for default methods and 316 for trained methods, Pro-Coffee achieves 331, 16.5% above the default average. We find a high correlation between a method's performance when classifying orthologs and its ability to correctly align proven binding sites. Not only has this interesting biological consequences, it also allows us to conclude that any method that is trained on the ortholog data set will result in functionally more informative alignments.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
    Publiziert von Oxford University Press
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  • 16
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    MCScanX: a toolkit for detection and evolutionary analysis of gene synteny and collinearity (2012)
    Oxford University Press
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    Publikationsdatum: 2012-04-15
    Beschreibung: MCScan is an algorithm able to scan multiple genomes or subgenomes in order to identify putative homologous chromosomal regions, and align these regions using genes as anchors. The MCScanX toolkit implements an adjusted MCScan algorithm for detection of synteny and collinearity that extends the original software by incorporating 14 utility programs for visualization of results and additional downstream analyses. Applications of MCScanX to several sequenced plant genomes and gene families are shown as examples. MCScanX can be used to effectively analyze chromosome structural changes, and reveal the history of gene family expansions that might contribute to the adaptation of lineages and taxa. An integrated view of various modes of gene duplication can supplement the traditional gene tree analysis in specific families. The source code and documentation of MCScanX are freely available at http://chibba.pgml.uga.edu/mcscan2/ .
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 17
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    A mostly traditional approach improves alignment of bisulfite-converted DNA (2012)
    Oxford University Press
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    Publikationsdatum: 2012-07-22
    Beschreibung: Cytosines in genomic DNA are sometimes methylated. This affects many biological processes and diseases. The standard way of measuring methylation is to use bisulfite, which converts unmethylated cytosines to thymines, then sequence the DNA and compare it to a reference genome sequence. We describe a method for the critical step of aligning the DNA reads to the correct genomic locations. Our method builds on classic alignment techniques, including likelihood-ratio scores and spaced seeds. In a realistic benchmark, our method has a better combination of sensitivity, specificity and speed than nine other high-throughput bisulfite aligners. This study enables more accurate and rational analysis of DNA methylation. It also illustrates how to adapt general-purpose alignment methods to a special case with distorted base patterns: this should be informative for other special cases such as ancient DNA and AT-rich genomes.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
    Publiziert von Oxford University Press
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  • 18
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    PhiSpy: a novel algorithm for finding prophages in bacterial genomes that combines similarity- and composition-based strategies (2012)
    Oxford University Press
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    Publikationsdatum: 2012-09-13
    Beschreibung: Prophages are phages in lysogeny that are integrated into, and replicated as part of, the host bacterial genome. These mobile elements can have tremendous impact on their bacterial hosts’ genomes and phenotypes, which may lead to strain emergence and diversification, increased virulence or antibiotic resistance. However, finding prophages in microbial genomes remains a problem with no definitive solution. The majority of existing tools rely on detecting genomic regions enriched in protein-coding genes with known phage homologs, which hinders the de novo discovery of phage regions. In this study, a weighted phage detection algorithm, PhiSpy was developed based on seven distinctive characteristics of prophages, i.e. protein length, transcription strand directionality, customized AT and GC skew, the abundance of unique phage words, phage insertion points and the similarity of phage proteins. The first five characteristics are capable of identifying prophages without any sequence similarity with known phage genes. PhiSpy locates prophages by ranking genomic regions enriched in distinctive phage traits, which leads to the successful prediction of 94% of prophages in 50 complete bacterial genomes with a 6% false-negative rate and a 0.66% false-positive rate.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
    Publiziert von Oxford University Press
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  • 19
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    Exploiting mid-range DNA patterns for sequence classification: binary abstraction Markov models (2012)
    Oxford University Press
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    Publikationsdatum: 2012-06-06
    Beschreibung: Messenger RNA sequences possess specific nucleotide patterns distinguishing them from non-coding genomic sequences. In this study, we explore the utilization of modified Markov models to analyze sequences up to 44 bp, far beyond the 8-bp limit of conventional Markov models, for exon/intron discrimination. In order to analyze nucleotide sequences of this length, their information content is first reduced by conversion into shorter binary patterns via the application of numerous abstraction schemes. After the conversion of genomic sequences to binary strings, homogenous Markov models trained on the binary sequences are used to discriminate between exons and introns. We term this approach the Binary Abstraction Markov Model (BAMM). High-quality abstraction schemes for exon/intron discrimination are selected using optimization algorithms on supercomputers. The best MM classifiers are then combined using support vector machines into a single classifier. With this approach, over 95% classification accuracy is achieved without taking reading frame into account. With further development, the BAMM approach can be applied to sequences lacking the genetic code such as ncRNAs and 5'-untranslated regions.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
    Publiziert von Oxford University Press
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  • 20
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    New methods for finding common insertion sites and co-occurring common insertion sites in transposon- and virus-based genetic screens (2012)
    Oxford University Press
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    Publikationsdatum: 2012-05-13
    Beschreibung: Insertional mutagenesis screens in mice are used to identify individual genes that drive tumor formation. In these screens, candidate cancer genes are identified if their genomic location is proximal to a common insertion site (CIS) defined by high rates of transposon or retroviral insertions in a given genomic window. In this article, we describe a new method for defining CISs based on a Poisson distribution, the Poisson Regression Insertion Model, and show that this new method is an improvement over previously described methods. We also describe a modification of the method that can identify pairs and higher orders of co-occurring common insertion sites. We apply these methods to two data sets, one generated in a transposon-based screen for gastrointestinal tract cancer genes and another based on the set of retroviral insertions in the Retroviral Tagged Cancer Gene Database. We show that the new methods identify more relevant candidate genes and candidate gene pairs than found using previous methods. Identification of the biologically relevant set of mutations that occur in a single cell and cause tumor progression will aid in the rational design of single and combinatorial therapies in the upcoming age of personalized cancer therapy.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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    Modelling pig sector dynamic adjustment to livestock epidemics with stochastic-duration trade disruptions (2011)
    Oxford University Press
    Details
    Publikationsdatum: 2011-11-24
    Beschreibung: We use a stochastic dynamic programming model to simulate the market implications of alternative foot and mouth disease scenarios in the Finnish pig sector. The model considers the dynamics of animal stock adjustment and price movements when the duration of export disruptions is unknown. Explicit treatment of these issues is crucial in the economic analysis of livestock epidemics, especially if there is a risk of a prolonged export ban. Results suggest that the risk of a prolonged ban increases disease losses considerably. It also increases economic benefits from production adjustments.
    Schlagwort(e): C61 - Optimization Techniques ; Programming Models ; Dynamic Analysis, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0165-1587
    Digitale ISSN: 1464-3618
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
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    Is embedding entailed in consumer valuation of food safety characteristics? (2011)
    Oxford University Press
    Details
    Publikationsdatum: 2011-11-24
    Beschreibung: Consumers' preferences for food safety characteristics are investigated with a particular focus on the existence of an embedding effect. Embedding exists if consumer valuation of food safety is insensitive to scope. We conduct between-attribute external tests for embedding in two choice experiments concerning the value of food safety attributes in minced pork and chicken breasts. We find no evidence of embedding neither when using food safety attributes that are not close substitutes and which exhibit both private and public good characteristics, nor when using food safety attributes that are closer substitutes and which have primarily private good characteristics.
    Schlagwort(e): Q10 - General, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0165-1587
    Digitale ISSN: 1464-3618
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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  • 23
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    Intangible expenses: a solution to increase the French wine industry performance? (2011)
    Oxford University Press
    Details
    Publikationsdatum: 2011-11-24
    Beschreibung: This paper presents an empirical investigation of the link between intangible expenses of French wine companies and their financial performance. A flexible moment-based approach is used to analyse the impact of tangible and intangible expenses on the mean, variance and skewness of profit. Econometric evidence shows that a high level of intangible expenses has a positive impact on performance by increasing the expected profit and reducing variance risk. A lower level of intangible expenses reduces risk and mean of profit of corporations. This study provides insights on the use of intangible expenses as a risk management tool.
    Schlagwort(e): G32 - Financing Policy ; Financial Risk and Risk Management ; Capital and Ownership Structure, Q12 - Micro Analysis of Farm Firms, Farm Households, and Farm Input Markets, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 0165-1587
    Digitale ISSN: 1464-3618
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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  • 24
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    Consumer inferences of food safety and quality (2011)
    Oxford University Press
    Details
    Publikationsdatum: 2011-11-24
    Beschreibung: Economists frequently use choice experiments (CEs) to evaluate demand for new attributes in food products. Using a split-sample experimental design focused on demand for pork chop attributes, we find consumer inferences regarding food safety and quality to impact estimates of marginal willingness to pay, market participation, policy appropriateness and consumer welfare effects. Our results suggest that interpretation of findings should be noted as conditional on attributes included in original analyses. A split-sample experimental approach involving multiple CE designs is described and suggested to practitioners to better consider consumer inference effects in future studies.
    Schlagwort(e): B40 - General, D12 - Consumer Economics: Empirical Analysis, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0165-1587
    Digitale ISSN: 1464-3618
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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  • 25
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    Consumers' preferences for geographical origin labels: evidence from the Canadian olive oil market (2011)
    Oxford University Press
    Details
    Publikationsdatum: 2011-11-24
    Beschreibung: Geographical origin labels are important information and marketing tools and have recently become a central component of EU agricultural promotion. We consider demand in a non-EU export market for two distinct label types: country of origin (COO) and geographical indications (GIs). Additionally, two types of GIs, ‘protected designations of origin’ (PDOs) and ‘protected GIs’ (PGIs) are considered. Empirical findings indicate consumers’ willingness to pay varies with the oil's COO and is greater for GIs than for non-GIs from a given country. Weaker evidence that consumers value PDOs more than PGIs is also found.
    Schlagwort(e): C25 - Discrete Regression and Qualitative Choice Models, D12 - Consumer Economics: Empirical Analysis, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 0165-1587
    Digitale ISSN: 1464-3618
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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  • 26
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    Chain interdependencies, measurement problems and efficient governance structure: cooperatives versus publicly listed firms (2012)
    Oxford University Press
    Details
    Publikationsdatum: 2012-03-08
    Beschreibung: We determine the circumstances when the absence of public listing, often believed to be a disadvantage, makes a cooperative the unique efficient governance structure. This is established in a multi-task principal–agent model, capturing that cooperatives are not publicly listed and their CEOs have to bring the downstream enterprise to value as well as to serve upstream member interests. Not having a public listing prevents the CEO from choosing the level of the downstream activities too high. Cooperatives are uniquely efficient when the upstream marginal product multiplied with a function increasing in the strength of the chain complementarities is higher than the downstream marginal product.
    Schlagwort(e): D21 - Firm Behavior, L23 - Organization of Production, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 0165-1587
    Digitale ISSN: 1464-3618
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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  • 27
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    Is producing a private label counterproductive for a branded manufacturer? (2012)
    Oxford University Press
    Details
    Publikationsdatum: 2012-03-08
    Beschreibung: Branded food manufacturers vindicate the use of excess production capacities to justify their production of retailers’ brands. We study the distributor's and food manufacturer's private label (PL) strategy for production within a framework featuring endogenous store brand quality, bargaining power, possible differences in production technology and potential capacity constraints for the branded manufacturer. Depending on the structure of capacity constraint (applying to both products or to the PL only), we find that the retailer may prefer to choose an independent firm for the production of the store brand whereas the branded manufacturer is chosen in the case of excess capacity.
    Schlagwort(e): L11 - Production, Pricing, and Market Structure ; Size Distribution of Firms, L13 - Oligopoly and Other Imperfect Markets, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 0165-1587
    Digitale ISSN: 1464-3618
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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  • 28
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    Cooperation against theft: A test of incentives for water management In Tunisia (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-01-22
    Beschreibung: Water theft carried out by manipulating water meters constrains volumetric pricing in semi-arid regions. Cooperative management can reduce theft and improve incentives for efficient water use by inducing peer monitoring. Using a theoretical model, we show that theft is more likely when prices are high, punishments are weak, and cooperatives are large. We also show how cooperative membership and punishment levels are determined endogenously by constraints on monitoring. We test the model on data from Tunisia for the years 2001–2003, relying on instruments that proxy for unobservable monitoring costs. The results confirm that well-designed incentives can reduce theft, and that constraints on monitoring costs affect institutional design.
    Schlagwort(e): D82 - Asymmetric and Private Information, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness, Q15 - Land Ownership and Tenure ; Land Reform ; Land Use ; Irrigation, Q25 - Water
    Print ISSN: 0002-9092
    Digitale ISSN: 1467-8276
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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  • 29
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    Isoform-level gene signature improves prognostic stratification and accurately classifies glioblastoma subtypes (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-05-01
    Beschreibung: Molecular stratification of tumors is essential for developing personalized therapies. Although patient stratification strategies have been successful; computational methods to accurately translate the gene-signature from high-throughput platform to a clinically adaptable low-dimensional platform are currently lacking. Here, we describe PIGExClass (platform-independent isoform-level gene-expression based classification-system), a novel computational approach to derive and then transfer gene-signatures from one analytical platform to another. We applied PIGExClass to design a reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) based molecular-subtyping assay for glioblastoma multiforme (GBM), the most aggressive primary brain tumors. Unsupervised clustering of TCGA (the Cancer Genome Altas Consortium) GBM samples, based on isoform-level gene-expression profiles, recaptured the four known molecular subgroups but switched the subtype for 19% of the samples, resulting in significant ( P = 0.0103) survival differences among the refined subgroups. PIGExClass derived four-class classifier, which requires only 121 transcript-variants, assigns GBM patients’ molecular subtype with 92% accuracy. This classifier was translated to an RT-qPCR assay and validated in an independent cohort of 206 GBM samples. Our results demonstrate the efficacy of PIGExClass in the design of clinically adaptable molecular subtyping assay and have implications for developing robust diagnostic assays for cancer patient stratification.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 30
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    fourSig: a method for determining chromosomal interactions in 4C-Seq data (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-05-01
    Beschreibung: The ability to correlate chromosome conformation and gene expression gives a great deal of information regarding the strategies used by a cell to properly regulate gene activity. 4C-Seq is a relatively new and increasingly popular technology where the set of genomic interactions generated by a single point in the genome can be determined. 4C-Seq experiments generate large, complicated data sets and it is imperative that signal is properly distinguished from noise. Currently, there are a limited number of methods for analyzing 4C-Seq data. Here, we present a new method, fourSig , which in addition to being precise and simple to use also includes a new feature that prioritizes detected interactions. Our results demonstrate the efficacy of fourSig with previously published and novel 4C-Seq data sets and show that our significance prioritization correlates with the ability to reproducibly detect interactions among replicates.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
    Publiziert von Oxford University Press
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    The Behavior of Bid-Ask Spreads in the Electronically-Traded Corn Futures Market (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-03-21
    Beschreibung: This is the first paper to analyze liquidity costs in agricultural futures markets based on the observed bid-ask spread (BAS) faced by market participants. The results reveal a highly liquid corn market that mostly offers order execution at minimum cost. The BAS responds negatively to volume and positively to price volatility, but also affects volume traded and price volatility. While statistically significant, these responses on a cents/bushel or a percentage basis are generally small. Liquidity costs are also virtually impervious to short-term changes in demand for spreading and trend-following trader activity, as well as differences from day-of-the-week changes in market activity. Much larger cents/bushel and percentage changes in BAS occur during commodity index trader roll periods and on USDA report release days. The roll period findings indicate a sunshine trading effect, while announcement effects identify the importance of unexpected information and adverse selection on order execution costs. Overall, our research demonstrates that the transition to electronic trading in the corn futures market has led to low and stable liquidity costs, despite the market turbulence in 2008–2009.
    Schlagwort(e): C36- Instrumental Variables (IV) Estimation, G12 - Asset Pricing ; Trading volume ; Bond Interest Rates, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 0002-9092
    Digitale ISSN: 1467-8276
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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  • 32
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    Angel Investment and Collective Agricultural Marketing: The Case of the Minnesota Food Network (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-03-21
    Beschreibung: The Minnesota Food Network is a limited liability company comprised of 52 farmers producing a variety of high-quality, sustainably produced agricultural products in southern Minnesota. The network's goal is to develop a regional food system to provide locally grown food at a price that "is fair" to both consumers and producers. This case outlines the challenges that the network faces in their efforts to expand to take advantage of a market opportunity. One of their biggest challenges is that they face high operating costs because of their disaggregated distribution system and need to purchase a distribution and storage facility and two vehicles. They will fund the purchase of a building through an angel investor. An angel investor is necessary because the network cannot sustain traditional loan payments in its current form. Students are asked to consider a number of questions pertaining to the decisions in this case outlined in the final section of the case study.
    Schlagwort(e): A22 - Undergraduate, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0002-9092
    Digitale ISSN: 1467-8276
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
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  • 33
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    Social Networks and New Product Choice (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-03-21
    Beschreibung: To successfully market new products in a social network it is essential to identify influential individuals whose product recommendations influence the consumption choices of their peers. In this study, we use spatial econometric methods to determine how individuals revise their preferences for product attributes when exposed to product recommendations from peers, and how different individuals who vary in their degree of network connectedness exert influence on the product choices of others. We find evidence that consumers look to others for guidance from peers in their preference for subjective, taste-specific parameters, but tend not to respond to peer price choices. Our spatial methods allow us to empirically determine the influence exerted by individual members on the consumption choices of other members of the social network. We find that connected members of the social network are not always the most influential in revising the consumption choices of others. Our estimates reveal that network proximity explains only 8.8% of influence.
    Schlagwort(e): D12 - Consumer Economics: Empirical Analysis, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 0002-9092
    Digitale ISSN: 1467-8276
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
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    High-resolution functional annotation of human transcriptome: predicting isoform functions by a novel multiple instance-based label propagation method (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-04-03
    Beschreibung: Alternative transcript processing is an important mechanism for generating functional diversity in genes. However, little is known about the precise functions of individual isoforms. In fact, proteins (translated from transcript isoforms), not genes, are the function carriers. By integrating multiple human RNA-seq data sets, we carried out the first systematic prediction of isoform functions, enabling high-resolution functional annotation of human transcriptome. Unlike gene function prediction, isoform function prediction faces a unique challenge: the lack of the training data—all known functional annotations are at the gene level. To address this challenge, we modelled the gene–isoform relationships as multiple instance data and developed a novel label propagation method to predict functions. Our method achieved an average area under the receiver operating characteristic curve of 0.67 and assigned functions to 15 572 isoforms. Interestingly, we observed that different functions have different sensitivities to alternative isoform processing, and that the function diversity of isoforms from the same gene is positively correlated with their tissue expression diversity. Finally, we surveyed the literature to validate our predictions for a number of apoptotic genes. Strikingly, for the famous ‘TP53’ gene, we not only accurately identified the apoptosis regulation function of its five isoforms, but also correctly predicted the precise direction of the regulation.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
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    Behavioral Responses and the Impact of New Agricultural Technologies: Evidence from a Double-blind Field Experiment in Tanzania (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-04-05
    Beschreibung: Randomized controlled trials (RCTs) in the social sciences are typically not double-blind, so participants know they are "treated" and will adjust their behavior accordingly. Such effort responses complicate the assessment of impact. To gauge the potential magnitude of effort responses we implement a conventional RCT and double-blind trial in rural Tanzania, and randomly allocate modern and traditional cowpea seed varieties to a sample of farmers. Effort responses can be quantitatively important—for our case they explain the entire "treatment effect on the treated" as measured in a conventional economic RCT. Specifically, harvests are the same for people who know they received the modern seeds and for people who did not know what type of seeds they got; however, people who knew they had received the traditional seeds did much worse. Importantly, we also find that most of the behavioral response is unobserved by the analyst, or at least not readily captured using coarse, standard controls.
    Schlagwort(e): Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 0002-9092
    Digitale ISSN: 1467-8276
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
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    Efficient large-scale protein sequence comparison and gene matching to identify orthologs and co-orthologs (2012)
    Oxford University Press
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    Publikationsdatum: 2012-03-29
    Beschreibung: Broadly, computational approaches for ortholog assignment is a three steps process: (i) identify all putative homologs between the genomes, (ii) identify gene anchors and (iii) link anchors to identify best gene matches given their order and context. In this article, we engineer two methods to improve two important aspects of this pipeline [specifically steps (ii) and (iii)]. First, computing sequence similarity data [step (i)] is a computationally intensive task for large sequence sets, creating a bottleneck in the ortholog assignment pipeline. We have designed a fast and highly scalable sort-join method (afree) based on k -mer counts to rapidly compare all pairs of sequences in a large protein sequence set to identify putative homologs. Second, availability of complex genomes containing large gene families with prevalence of complex evolutionary events, such as duplications, has made the task of assigning orthologs and co-orthologs difficult. Here, we have developed an iterative graph matching strategy where at each iteration the best gene assignments are identified resulting in a set of orthologs and co-orthologs. We find that the afree algorithm is faster than existing methods and maintains high accuracy in identifying similar genes. The iterative graph matching strategy also showed high accuracy in identifying complex gene relationships. Standalone afree available from http://vbc.med.monash.edu.au/~kmahmood/afree . EGM2, complete ortholog assignment pipeline (including afree and the iterative graph matching method) available from http://vbc.med.monash.edu.au/~kmahmood/EGM2 .
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
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    The allele distribution in next-generation sequencing data sets is accurately described as the result of a stochastic branching process (2012)
    Oxford University Press
    Details
    Publikationsdatum: 2012-03-29
    Beschreibung: With the availability of next-generation sequencing (NGS) technology, it is expected that sequence variants may be called on a genomic scale. Here, we demonstrate that a deeper understanding of the distribution of the variant call frequencies at heterozygous loci in NGS data sets is a prerequisite for sensitive variant detection. We model the crucial steps in an NGS protocol as a stochastic branching process and derive a mathematical framework for the expected distribution of alleles at heterozygous loci before measurement that is sequencing. We confirm our theoretical results by analyzing technical replicates of human exome data and demonstrate that the variance of allele frequencies at heterozygous loci is higher than expected by a simple binomial distribution. Due to this high variance, mutation callers relying on binomial distributed priors are less sensitive for heterozygous variants that deviate strongly from the expected mean frequency. Our results also indicate that error rates can be reduced to a greater degree by technical replicates than by increasing sequencing depth.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
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    Unsupervised discovery of microbial population structure within metagenomes using nucleotide base composition (2012)
    Oxford University Press
    Details
    Publikationsdatum: 2012-03-14
    Beschreibung: An approach to infer the unknown microbial population structure within a metagenome is to cluster nucleotide sequences based on common patterns in base composition, otherwise referred to as binning. When functional roles are assigned to the identified populations, a deeper understanding of microbial communities can be attained, more so than gene-centric approaches that explore overall functionality. In this study, we propose an unsupervised, model-based binning method with two clustering tiers, which uses a novel transformation of the oligonucleotide frequency-derived error gradient and GC content to generate coarse groups at the first tier of clustering; and tetranucleotide frequency to refine these groups at the secondary clustering tier. The proposed method has a demonstrated improvement over PhyloPythia, S-GSOM, TACOA and TaxSOM on all three benchmarks that were used for evaluation in this study. The proposed method is then applied to a pyrosequenced metagenomic library of mud volcano sediment sampled in southwestern Taiwan, with the inferred population structure validated against complementary sequencing of 16S ribosomal RNA marker genes. Finally, the proposed method was further validated against four publicly available metagenomes, including a highly complex Antarctic whale-fall bone sample, which was previously assumed to be too complex for binning prior to functional analysis.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
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    Structural change in European calf markets: decoupling and the blue tongue disease (2011)
    Oxford University Press
    Details
    Publikationsdatum: 2011-12-27
    Beschreibung: European cattle markets have recently undergone significant change. We explore the simultaneous impacts of agricultural policy reform and the occurrence of an animal health crisis on spatial interdependencies of calf prices of four major European Union markets. The markets are found to be integrated. Price shocks are rapidly absorbed. We find that the member state specific implementations of the 2003 Common Agricultural Policy reforms significantly affected prices of both the national market and of other member states. The blue tongue disease further induced structural change. Using counterfactual scenarios, we show that the decoupling of payments from production led to reduced calf prices.
    Schlagwort(e): C32 - Time-Series Models, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0165-1587
    Digitale ISSN: 1464-3618
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
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    NTRFinder: a software tool to find nested tandem repeats (2012)
    Oxford University Press
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    Publikationsdatum: 2012-02-17
    Beschreibung: We introduce the software tool NTRFinder to search for a complex repetitive structure in DNA we call a nested tandem repeat (NTR). An NTR is a recurrence of two or more distinct tandem motifs interspersed with each other. We propose that NTRs can be used as phylogenetic and population markers. We have tested our algorithm on both real and simulated data, and present some real NTRs of interest. NTRFinder can be downloaded from http://www.maths.otago.ac.nz/~aamatroud/ .
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
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    sPARTA: a parallelized pipeline for integrated analysis of plant miRNA and cleaved mRNA data sets, including new miRNA target-identification software (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-10-10
    Beschreibung: Parallel analysis of RNA ends (PARE) is a technique utilizing high-throughput sequencing to profile uncapped, mRNA cleavage or decay products on a genome-wide basis. Tools currently available to validate miRNA targets using PARE data employ only annotated genes, whereas important targets may be found in unannotated genomic regions. To handle such cases and to scale to the growing availability of PARE data and genomes, we developed a new tool, ‘ sPARTA ’ (small RNA-PARE target analyzer) that utilizes a built-in, plant-focused target prediction module (aka ‘ miRferno ’). sPARTA not only exhibits an unprecedented gain in speed but also it shows greater predictive power by validating more targets, compared to a popular alternative. In addition, the novel ‘seed-free’ mode, optimized to find targets irrespective of complementarity in the seed-region, identifies novel intergenic targets. To fully capitalize on the novelty and strengths of sPARTA , we developed a web resource, ‘ comPARE ’, for plant miRNA target analysis; this facilitates the systematic identification and analysis of miRNA-target interactions across multiple species, integrated with visualization tools. This collation of high-throughput small RNA and PARE datasets from different genomes further facilitates re-evaluation of existing miRNA annotations, resulting in a ‘cleaner’ set of microRNAs.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
    Publiziert von Oxford University Press
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    A statistical model of ChIA-PET data for accurate detection of chromatin 3D interactions (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-10-10
    Beschreibung: Identification of three-dimensional (3D) interactions between regulatory elements across the genome is crucial to unravel the complex regulatory machinery that orchestrates proliferation and differentiation of cells. ChIA-PET is a novel method to identify such interactions, where physical contacts between regions bound by a specific protein are quantified using next-generation sequencing. However, determining the significance of the observed interaction frequencies in such datasets is challenging, and few methods have been proposed. Despite the fact that regions that are close in linear genomic distance have a much higher tendency to interact by chance, no methods to date are capable of taking such dependency into account. Here, we propose a statistical model taking into account the genomic distance relationship, as well as the general propensity of anchors to be involved in contacts overall. Using both real and simulated data, we show that the previously proposed statistical test, based on Fisher's exact test, leads to invalid results when data are dependent on genomic distance. We also evaluate our method on previously validated cell-line specific and constitutive 3D interactions, and show that relevant interactions are significant, while avoiding over-estimating the significance of short nearby interactions.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
    Publiziert von Oxford University Press
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  • 43
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    COMET: adaptive context-based modeling for ultrafast HIV-1 subtype identification (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-10-10
    Beschreibung: Viral sequence classification has wide applications in clinical, epidemiological, structural and functional categorization studies. Most existing approaches rely on an initial alignment step followed by classification based on phylogenetic or statistical algorithms. Here we present an ultrafast alignment-free subtyping tool for human immunodeficiency virus type one (HIV-1) adapted from Prediction by Partial Matching compression. This tool, named COMET, was compared to the widely used phylogeny-based REGA and SCUEAL tools using synthetic and clinical HIV data sets (1 090 698 and 10 625 sequences, respectively). COMET's sensitivity and specificity were comparable to or higher than the two other subtyping tools on both data sets for known subtypes. COMET also excelled in detecting and identifying new recombinant forms, a frequent feature of the HIV epidemic. Runtime comparisons showed that COMET was almost as fast as USEARCH. This study demonstrates the advantages of alignment-free classification of viral sequences, which feature high rates of variation, recombination and insertions/deletions. COMET is free to use via an online interface.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
    Publiziert von Oxford University Press
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  • 44
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    Large-scale modeling of condition-specific gene regulatory networks by information integration and inference (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-11-28
    Beschreibung: Understanding how regulatory networks globally coordinate the response of a cell to changing conditions, such as perturbations by shifting environments, is an elementary challenge in systems biology which has yet to be met. Genome-wide gene expression measurements are high dimensional as these are reflecting the condition-specific interplay of thousands of cellular components. The integration of prior biological knowledge into the modeling process of systems-wide gene regulation enables the large-scale interpretation of gene expression signals in the context of known regulatory relations. We developed COGERE ( http://mips.helmholtz-muenchen.de/cogere ), a method for the inference of condition-specific gene regulatory networks in human and mouse. We integrated existing knowledge of regulatory interactions from multiple sources to a comprehensive model of prior information. COGERE infers condition-specific regulation by evaluating the mutual dependency between regulator (transcription factor or miRNA) and target gene expression using prior information. This dependency is scored by the non-parametric, nonlinear correlation coefficient 2 (eta squared) that is derived by a two-way analysis of variance. We show that COGERE significantly outperforms alternative methods in predicting condition-specific gene regulatory networks on simulated data sets. Furthermore, by inferring the cancer-specific gene regulatory network from the NCI-60 expression study, we demonstrate the utility of COGERE to promote hypothesis-driven clinical research.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
    Publiziert von Oxford University Press
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  • 45
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    Gone in Ten Minutes: Intraday Evidence of Announcement Effects in the Electronic Corn Futures Market (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-09-06
    Beschreibung: This article investigates the announcement effects of major USDA reports using intraday Chicago Board of Trade corn futures prices and trading volume from the electronic trading platform for July 2009 to May 2012. Focusing on intraday market reactions, we analyze the extent to which new information impacts and is rapidly reflected in prices. Results show that USDA reports contain substantial information for market participants. Strongest price reactions to the releases are found immediately after the market opens, and market reactions persist for approximately ten minutes. The electronic corn futures market quickly incorporates this new public information, and little evidence exists to support systematic under- or overreactions in prices. Other more subtle reactions occur in the last trading session before USDA announcements as traders adjust their market exposure in anticipation of the release.
    Schlagwort(e): D80 - General, G14 - Information and Market Efficiency ; Event Studies, Q11 - Aggregate Supply and Demand Analysis ; Prices, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 2040-5790
    Digitale ISSN: 2040-5804
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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  • 46
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    Determinants of Occupational Safety for Agribusiness Workers (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-09-06
    Beschreibung: Increases in crop yields and changing cropping patterns have placed stress on agribusiness handling and storage facilities. The objective of this research is to gain insight into the relationship between safety culture and safety performance, and to identify the determinants of safety culture in agribusinesses. The research suggests that investments in labor inputs such as increased training, consistent discipline, and recognition of safety achievements all increase safety culture. Furthermore, improvements in employee perceptions of safety culture have a positive impact on reducing employee injuries. Congress has recently funded nine centers to work on occupational health and safety research in agriculture, fisheries, and forestry.
    Schlagwort(e): J43 - Agricultural Labor Markets, L66 - Food ; Beverages ; Cosmetics ; Tobacco ; Wine and Spirits, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 2040-5790
    Digitale ISSN: 2040-5804
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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    Futures Market Failure? (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-12-13
    Beschreibung: In a well-functioning futures market, the futures price at expiration equals the price of the underlying asset. This condition failed to hold in grain markets for most of 2005-2010, calling into question the ability of these markets to perform their price discovery and risk management functions. During this period, futures contracts expired up to 35% above the cash grain price. We develop a dynamic rational expectations model of commodity storage that explains how these recent convergence failures were generated by the institutional structure of the delivery system. When delivery occurs on a grain futures contract, the firm on the short side of the market provides a delivery instrument (a warehouse receipt or shipping certificate) to the firm on the long side of the market. The firm taking delivery may hold the delivery instrument indefinitely, providing it pays a daily storage rate. The futures exchange sets the maximum allowable storage rate at a fixed value. We show that non-convergence arises in equilibrium when the market price of physical grain storage exceeds the maximum storage rate on delivery instruments. We call the difference between the price of carrying physical grain and the maximum storage rate the wedge , and demonstrate theoretically and empirically that the magnitude of the non-convergence equals the expected present discounted value of a function of future wedges.
    Schlagwort(e): G13 - Contingent Pricing ; Futures Pricing, G14 - Information and Market Efficiency ; Event Studies, Q11 - Aggregate Supply and Demand Analysis ; Prices, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 0002-9092
    Digitale ISSN: 1467-8276
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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  • 48
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    ptRNApred: computational identification and classification of post-transcriptional RNA (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-12-17
    Beschreibung: Non-coding RNAs (ncRNAs) are known to play important functional roles in the cell. However, their identification and recognition in genomic sequences remains challenging. In silico methods, such as classification tools, offer a fast and reliable way for such screening and multiple classifiers have already been developed to predict well-defined subfamilies of RNA. So far, however, out of all the ncRNAs, only tRNA, miRNA and snoRNA can be predicted with a satisfying sensitivity and specificity. We here present ptRNApred , a tool to detect and classify subclasses of non-coding RNA that are involved in the regulation of post-transcriptional modifications or DNA replication, which we here call post-transcriptional RNA (ptRNA). It (i) detects RNA sequences coding for post-transcriptional RNA from the genomic sequence with an overall sensitivity of 91% and a specificity of 94% and (ii) predicts ptRNA-subclasses that exist in eukaryotes: snRNA, snoRNA, RNase P, RNase MRP, Y RNA or telomerase RNA. AVAILABILITY: The ptRNApred software is open for public use on http://www.ptrnapred.org/ .
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
    Publiziert von Oxford University Press
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  • 49
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    The eSNV-detect: a computational system to identify expressed single nucleotide variants from transcriptome sequencing data (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-12-17
    Beschreibung: Rapid development of next generation sequencing technology has enabled the identification of genomic alterations from short sequencing reads. There are a number of software pipelines available for calling single nucleotide variants from genomic DNA but, no comprehensive pipelines to identify, annotate and prioritize expressed SNVs (eSNVs) from non-directional paired-end RNA-Seq data. We have developed the eSNV-Detect, a novel computational system, which utilizes data from multiple aligners to call, even at low read depths, and rank variants from RNA-Seq. Multi-platform comparisons with the eSNV-Detect variant candidates were performed. The method was first applied to RNA-Seq from a lymphoblastoid cell-line, achieving 99.7% precision and 91.0% sensitivity in the expressed SNPs for the matching HumanOmni2.5 BeadChip data. Comparison of RNA-Seq eSNV candidates from 25 ER+ breast tumors from The Cancer Genome Atlas (TCGA) project with whole exome coding data showed 90.6–96.8% precision and 91.6–95.7% sensitivity. Contrasting single-cell mRNA-Seq variants with matching traditional multicellular RNA-Seq data for the MD-MB231 breast cancer cell-line delineated variant heterogeneity among the single-cells. Further, Sanger sequencing validation was performed for an ER+ breast tumor with paired normal adjacent tissue validating 29 out of 31 candidate eSNVs. The source code and user manuals of the eSNV-Detect pipeline for Sun Grid Engine and virtual machine are available at http://bioinformaticstools.mayo.edu/research/esnv-detect/ .
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
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  • 50
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    Price Explosiveness, Speculation, and Grain Futures Prices (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-12-13
    Beschreibung: A recently developed testing procedure is used to detect and date-stamp explosive episodes ("bubbles") in corn, soybean, and wheat futures markets during 2004–2013. We find that the markets experienced price explosiveness only approximately two percent of the time and, when bubbles do occur, they are generally short-lived and small in magnitude. The correspondence between observed price spikes and bubbles is rather low, with a large portion of the price explosiveness occurring during downward price movements. Commodity index trader positions do not significantly affect the probability of a positive bubble occurring in grain futures markets, which directly contradicts the argument (the "Masters Hypothesis") that waves of index investment distorted underlying supply-and-demand relationships and led to a series of massive bubbles in agricultural futures markets. In addition, commodity index trader positions tend to reduce negative bubble occurrence, while general speculative activity as measured by Working's T reduces the probability of a positive bubble. There is some evidence that the positions of noncommercial traders have a direct effect on positive bubble occurrence, but the effect declines when accounting for the composition of other traders in the market. Overall, speculation has little effect or negative effects on price explosiveness. Finally, positive bubbles are more likely to occur in the presence of low inventories, strong exports, a weak U.S. dollar, and booming economic growth, whereas negative bubbles are more likely to occur with large inventories, weak exports, and stagnant economic growth.
    Schlagwort(e): D84 - Expectations ; Speculations, G12 - Asset Pricing ; Trading volume ; Bond Interest Rates, G13 - Contingent Pricing ; Futures Pricing, G14 - Information and Market Efficiency ; Event Studies, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness, Q41 - Demand and Supply
    Print ISSN: 0002-9092
    Digitale ISSN: 1467-8276
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
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    Hunting complex differential gene interaction patterns across molecular contexts (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-04-15
    Beschreibung: Heterogeneity in genetic networks across different signaling molecular contexts can suggest molecular regulatory mechanisms. Here we describe a comparative chi-square analysis (CP 2 ) method, considerably more flexible and effective than other alternatives, to screen large gene expression data sets for conserved and differential interactions. CP 2 decomposes interactions across conditions to assess homogeneity and heterogeneity. Theoretically, we prove an asymptotic chi-square null distribution for the interaction heterogeneity statistic. Empirically, on synthetic yeast cell cycle data, CP 2 achieved much higher statistical power in detecting differential networks than alternative approaches. We applied CP 2 to Drosophila melanogaster wing gene expression arrays collected under normal conditions, and conditions with overexpressed E2F and Cabut, two transcription factor complexes that promote ectopic cell cycling. The resulting differential networks suggest a mechanism by which E2F and Cabut regulate distinct gene interactions, while still sharing a small core network. Thus, CP 2 is sensitive in detecting network rewiring, useful in comparing related biological systems.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
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    DNA motif elucidation using belief propagation (2013)
    Oxford University Press
    Details
    Publikationsdatum: 2013-09-06
    Beschreibung: Protein-binding microarray (PBM) is a high-throughout platform that can measure the DNA-binding preference of a protein in a comprehensive and unbiased manner. A typical PBM experiment can measure binding signal intensities of a protein to all the possible DNA k-mers (k = 8 ~10); such comprehensive binding affinity data usually need to be reduced and represented as motif models before they can be further analyzed and applied. Since proteins can often bind to DNA in multiple modes, one of the major challenges is to decompose the comprehensive affinity data into multimodal motif representations. Here, we describe a new algorithm that uses Hidden Markov Models (HMMs) and can derive precise and multimodal motifs using belief propagations. We describe an HMM-based approach using belief propagations (kmerHMM), which accepts and preprocesses PBM probe raw data into median-binding intensities of individual k-mers. The k-mers are ranked and aligned for training an HMM as the underlying motif representation. Multiple motifs are then extracted from the HMM using belief propagations. Comparisons of kmerHMM with other leading methods on several data sets demonstrated its effectiveness and uniqueness. Especially, it achieved the best performance on more than half of the data sets. In addition, the multiple binding modes derived by kmerHMM are biologically meaningful and will be useful in interpreting other genome-wide data such as those generated from ChIP-seq. The executables and source codes are available at the authors’ websites: e.g. http://www.cs.toronto.edu/~wkc/kmerHMM .
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
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  • 53
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    Improved search heuristics find 20 000 new alignments between human and mouse genomes (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-04-15
    Beschreibung: Sequence similarity search is a fundamental way of analyzing nucleotide sequences. Despite decades of research, this is not a solved problem because there exist many similarities that are not found by current methods. Search methods are typically based on a seed-and-extend approach, which has many variants (e.g. spaced seeds, transition seeds), and it remains unclear how to optimize this approach. This study designs and tests seeding methods for inter-mammal and inter-insect genome comparison. By considering substitution patterns of real genomes, we design sets of multiple complementary transition seeds, which have better performance (sensitivity per run time) than previous seeding strategies. Often the best seed patterns have more transition positions than those used previously. We also point out that recent computer memory sizes (e.g. 60 GB) make it feasible to use multiple (e.g. eight) seeds for whole mammal genomes. Interestingly, the most sensitive settings achieve diminishing returns for human–dog and melanogaster–pseudoobscura comparisons, but not for human–mouse, which suggests that we still miss many human–mouse alignments. Our optimized heuristics find ~20 000 new human–mouse alignments that are missing from the standard UCSC alignments. We tabulate seed patterns and parameters that work well so they can be used in future research.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
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    EDDY: a novel statistical gene set test method to detect differential genetic dependencies (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-04-15
    Beschreibung: Identifying differential features between conditions is a popular approach to understanding molecular features and their mechanisms underlying a biological process of particular interest. Although many tests for identifying differential expression of gene or gene sets have been proposed, there was limited success in developing methods for differential interactions of genes between conditions because of its computational complexity. We present a method for Evaluation of Dependency DifferentialitY (EDDY), which is a statistical test for differential dependencies of a set of genes between two conditions. Unlike previous methods focused on differential expression of individual genes or correlation changes of individual gene–gene interactions, EDDY compares two conditions by evaluating the probability distributions of dependency networks from genes. The method has been evaluated and compared with other methods through simulation studies, and application to glioblastoma multiforme data resulted in informative cancer and glioblastoma multiforme subtype-related findings. The comparison with Gene Set Enrichment Analysis, a differential expression-based method, revealed that EDDY identifies the gene sets that are complementary to those identified by Gene Set Enrichment Analysis. EDDY also showed much lower false positives than Gene Set Co-expression Analysis, a method based on correlation changes of individual gene–gene interactions, thus providing more informative results. The Java implementation of the algorithm is freely available to noncommercial users. Download from: http://biocomputing.tgen.org/software/EDDY .
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
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  • 55
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    Adapting Contract Theory to Fit Contract Farming (2014)
    Oxford University Press
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    Publikationsdatum: 2014-09-02
    Beschreibung: This article discusses the current state of contract theory and its usefulness for conceptualizing issues related to agricultural contracting. The paper will explore the limitations of existing theory for applied work, and what methodological improvements are needed to enhance the usefulness of the theory to agricultural economists. One pervasive problem is that the economic literature on contracts is rather fragmented and the various methodological strands are narrow in their focus. As such, agricultural economists should engage in methodological research to develop applied contracting models that can capture higher-order features of real-world agricultural contracts while delivering generalizable comparative statics predictions because contracting continues to expand along the entire modern food marketing channel. In the latter part of this article, a simple model is developed to illustrate how classic methodological approaches can be combined with recent developments in contract and game theory to construct applied theory models that are useful for capturing some important features of agricultural contracts.
    Schlagwort(e): D43 - Oligopoly and Other Forms of Market Imperfection, D82 - Asymmetric and Private Information, D86 - Economics of Contract: Theory, Q12 - Micro Analysis of Farm Firms, Farm Households, and Farm Input Markets, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 0002-9092
    Digitale ISSN: 1467-8276
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
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    Information, Mobile Telephony, and Traders' Search Behavior in Niger (2014)
    Oxford University Press
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    Publikationsdatum: 2014-09-02
    Beschreibung: Information and communications technologies have spread rapidly in developing countries. We investigate the impact of mobile phones on traders' search behavior in Niger by constructing a theoretical model of search in which traders engage in sequential search for the optimal sales price. Using a trader panel dataset spanning 2005–2007, we find empirical support for the model in that the duration of mobile phone coverage is associated with increased search activity. This effect evolves dynamically over time and is stronger for larger traders, who engage in arbitrage over longer distances. Results provide empirical evidence for the observed linkages between mobile telephony and price dispersion.
    Schlagwort(e): O10 - General, O30 - General, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 0002-9092
    Digitale ISSN: 1467-8276
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
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    Inferring population structure and relationship using minimal independent evolutionary markers in Y-chromosome: a hybrid approach of recursive feature selection for hierarchical clustering (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-09-02
    Beschreibung: Inundation of evolutionary markers expedited in Human Genome Project and 1000 Genome Consortium has necessitated pruning of redundant and dependent variables. Various computational tools based on machine-learning and data-mining methods like feature selection/extraction have been proposed to escape the curse of dimensionality in large datasets. Incidentally, evolutionary studies, primarily based on sequentially evolved variations have remained un-facilitated by such advances till date. Here, we present a novel approach of recursive feature selection for hierarchical clustering of Y-chromosomal SNPs/haplogroups to select a minimal set of independent markers, sufficient to infer population structure as precisely as deduced by a larger number of evolutionary markers. To validate the applicability of our approach, we optimally designed MALDI-TOF mass spectrometry-based multiplex to accommodate independent Y-chromosomal markers in a single multiplex and genotyped two geographically distinct Indian populations. An analysis of 105 world-wide populations reflected that 15 independent variations/markers were optimal in defining population structure parameters, such as F ST , molecular variance and correlation-based relationship. A subsequent addition of randomly selected markers had a negligible effect (close to zero, i.e. 1 x 10 –3 ) on these parameters. The study proves efficient in tracing complex population structures and deriving relationships among world-wide populations in a cost-effective and expedient manner.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
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    Multivariate inference of pathway activity in host immunity and response to therapeutics (2014)
    Oxford University Press
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    Publikationsdatum: 2014-09-17
    Beschreibung: Developing a quantitative view of how biological pathways are regulated in response to environmental factors is central for understanding of disease phenotypes. We present a computational framework, named Multivariate Inference of Pathway Activity (MIPA), which quantifies degree of activity induced in a biological pathway by computing five distinct measures from transcriptomic profiles of its member genes. Statistical significance of inferred activity is examined using multiple independent self-contained tests followed by a competitive analysis. The method incorporates a new algorithm to identify a subset of genes that may regulate the extent of activity induced in a pathway. We present an in-depth evaluation of specificity, robustness, and reproducibility of our method. We benchmarked MIPA's false positive rate at less than 1%. Using transcriptomic profiles representing distinct physiological and disease states, we illustrate applicability of our method in (i) identifying gene–gene interactions in autophagy-dependent response to Salmonella infection, (ii) uncovering gene–environment interactions in host response to bacterial and viral pathogens and (iii) identifying driver genes and processes that contribute to wound healing and response to anti-TNFα therapy. We provide relevant experimental validation that corroborates the accuracy and advantage of our method.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
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    MosaicSolver: a tool for determining recombinants of viral genomes from pileup data (2014)
    Oxford University Press
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    Publikationsdatum: 2014-09-17
    Beschreibung: Viral recombination is a key evolutionary mechanism, aiding escape from host immunity, contributing to changes in tropism and possibly assisting transmission across species barriers. The ability to determine whether recombination has occurred and to locate associated specific recombination junctions is thus of major importance in understanding emerging diseases and pathogenesis. This paper describes a method for determining recombinant mosaics (and their proportions) originating from two parent genomes, using high-throughput sequence data. The method involves setting the problem geometrically and the use of appropriately constrained quadratic programming. Recombinants of the honeybee deformed wing virus and the Varroa destructor virus-1 are inferred to illustrate the method from both siRNAs and reads sampling the viral genome population (cDNA library); our results are confirmed experimentally. Matlab software (MosaicSolver) is available.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
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    Distinguishing beliefs from preferences in food choice (2014)
    Oxford University Press
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    Publikationsdatum: 2014-08-02
    Beschreibung: In the past two decades, there has been an explosion of studies eliciting consumer willingness-to-pay for food attributes; however, this work has largely refrained from drawing a distinction between preferences for health, safety and quality on the one hand and consumers' subjective beliefs that the products studied possess these attributes, on the other. Using data from three experimental studies, along with structural economic models, we show that controlling for subjective beliefs can substantively alter the interpretation of results and the ultimate implications derived from a study. The results suggest the need to measure subjective beliefs in studies of consumer choice and to utilise the measures when making policy and marketing recommendations.
    Schlagwort(e): C91 - Laboratory, Individual Behavior, D83 - Search ; Learning ; Information and Knowledge ; Communication ; Belief, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0165-1587
    Digitale ISSN: 1464-3618
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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    Computational identification of functional introns: high positional conservation of introns that harbor RNA genes (2013)
    Oxford University Press
    Details
    Publikationsdatum: 2013-06-08
    Beschreibung: An appreciable fraction of introns is thought to have some function, but there is no obvious way to predict which specific intron is likely to be functional. We hypothesize that functional introns experience a different selection regime than non-functional ones and will therefore show distinct evolutionary histories. In particular, we expect functional introns to be more resistant to loss, and that this would be reflected in high conservation of their position with respect to the coding sequence. To test this hypothesis, we focused on introns whose function comes about from microRNAs and snoRNAs that are embedded within their sequence. We built a data set of orthologous genes across 28 eukaryotic species, reconstructed the evolutionary histories of their introns and compared functional introns with the rest of the introns. We found that, indeed, the position of microRNA- and snoRNA-bearing introns is significantly more conserved. In addition, we found that both families of RNA genes settled within introns early during metazoan evolution. We identified several easily computable intronic properties that can be used to detect functional introns in general, thereby suggesting a new strategy to pinpoint non-coding cellular functions.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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    CORECLUST: identification of the conserved CRM grammar together with prediction of gene regulation (2012)
    Oxford University Press
    Details
    Publikationsdatum: 2012-06-28
    Beschreibung: Identification of transcriptional regulatory regions and tracing their internal organization are important for understanding the eukaryotic cell machinery. Cis-regulatory modules (CRMs) of higher eukaryotes are believed to possess a regulatory ‘grammar’, or preferred arrangement of binding sites, that is crucial for proper regulation and thus tends to be evolutionarily conserved. Here, we present a method CORECLUST (COnservative REgulatory CLUster STructure) that predicts CRMs based on a set of positional weight matrices. Given regulatory regions of orthologous and/or co-regulated genes, CORECLUST constructs a CRM model by revealing the conserved rules that describe the relative location of binding sites. The constructed model may be consequently used for the genome-wide prediction of similar CRMs, and thus detection of co-regulated genes, and for the investigation of the regulatory grammar of the system. Compared with related methods, CORECLUST shows better performance at identification of CRMs conferring muscle-specific gene expression in vertebrates and early-developmental CRMs in Drosophila .
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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    i-cisTarget: an integrative genomics method for the prediction of regulatory features and cis-regulatory modules (2012)
    Oxford University Press
    Details
    Publikationsdatum: 2012-08-23
    Beschreibung: The field of regulatory genomics today is characterized by the generation of high-throughput data sets that capture genome-wide transcription factor (TF) binding, histone modifications, or DNAseI hypersensitive regions across many cell types and conditions. In this context, a critical question is how to make optimal use of these publicly available datasets when studying transcriptional regulation. Here, we address this question in Drosophila melanogaster for which a large number of high-throughput regulatory datasets are available. We developed i-cisTarget (where the ‘ i ’ stands for integrative ), for the first time enabling the discovery of different types of enriched ‘regulatory features’ in a set of co-regulated sequences in one analysis, being either TF motifs or ‘ in vivo ’ chromatin features, or combinations thereof. We have validated our approach on 15 co-expressed gene sets, 21 ChIP data sets, 628 curated gene sets and multiple individual case studies, and show that meaningful regulatory features can be confidently discovered; that bona fide enhancers can be identified, both by in vivo events and by TF motifs; and that combinations of in vivo events and TF motifs further increase the performance of enhancer prediction.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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    Consumer preferences for local production and other value-added label claims for a processed food product (2012)
    Oxford University Press
    Details
    Publikationsdatum: 2012-05-29
    Beschreibung: Using stated preference data from Kentucky and Ohio, USA, we estimate consumer willingness-to-pay for varieties of a processed food product (blackberry jam) that are differentiated with respect to their local production labelling and a series of other value-added claims. Results show that consumers were willing to pay more for the product indicating locally produced, produced in their state or in a well-identified multi-state region. Consumers were willing to purchase organic products, although there might be some confusion as to the meaning of the organic logo. Our results also supported the notion that consumers are willing to support small family farms.
    Schlagwort(e): Q11 - Aggregate Supply and Demand Analysis ; Prices, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 0165-1587
    Digitale ISSN: 1464-3618
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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    Dairy supply chain modernisation in Poland: what about those not keeping pace? (2012)
    Oxford University Press
    Details
    Publikationsdatum: 2012-05-29
    Beschreibung: This paper studies the determinants and consequences of heterogeneous market participation among Polish dairy farmers using a unique data set on supply chain characteristics and individuals with different market relationships. It investigates factors that cause households not to participate in the market and then estimates farm orientation effects on revenues, using semi-parametric methods. The key finding is that farms maintaining commercial dairy business were better off than those who ceased milk sales. However, detailed analysis shows that this difference could be attributed to supply chain modernisation and becomes insignificant once subsistence farmers are compared to commercial farms supplying the traditional marketing channel.
    Schlagwort(e): D22 - Firm Behavior: Empirical Analysis, Q12 - Micro Analysis of Farm Firms, Farm Households, and Farm Input Markets, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 0165-1587
    Digitale ISSN: 1464-3618
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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    Identifying subgroup markers in heterogeneous populations (2013)
    Oxford University Press
    Details
    Publikationsdatum: 2013-11-21
    Beschreibung: Traditional methods that aim to identify biomarkers that distinguish between two groups, like Significance Analysis of Microarrays or the t -test, perform optimally when such biomarkers show homogeneous behavior within each group and differential behavior between the groups. However, in many applications, this is not the case. Instead, a subgroup of samples in one group shows differential behavior with respect to all other samples. To successfully detect markers showing such imbalanced patterns of differential signal, a different approach is required. We propose a novel method, specifically designed for the Detection of Imbalanced Differential Signal (DIDS). We use an artificial dataset and a human breast cancer dataset to measure its performance and compare it with three traditional methods and four approaches that take imbalanced signal into account. Supported by extensive experimental results, we show that DIDS outperforms all other approaches in terms of power and positive predictive value. In a mouse breast cancer dataset, DIDS is the only approach that detects a functionally validated marker of chemotherapy resistance. DIDS can be applied to any continuous value data, including gene expression data, and in any context where imbalanced differential signal is manifested.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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    The Impact of Credit Constraints on Farm Households: Survey Results from India and China (2013)
    Oxford University Press
    Details
    Publikationsdatum: 2013-11-22
    Beschreibung: India and China have the largest farm-household populations in the world—populations that are also among the poorest. Among the many factors that affect farm livelihoods, access to credit has been identified as a significant barrier preventing the escape from poverty. While there has been significant research on credit constraints in developing countries, there is surprisingly little information pertaining to the actual impacts of credit constraints on household well-being. The objective of this paper is to investigate the impacts of credit constraints on various factors affecting farm households, such as physical and human capital formation, agricultural inputs applications, consumption smoothing, and wage-seeking behavior using direct elicitation. This paper contributes to the literature and policy debates by comparing the effects of credit constraints in China and India as surveyed in 2008–2009. The analytical results and data demonstrate that binding credit constraints adversely affect a broad range of production and livelihood choices. We empirically show that credit constraints negatively affect food consumption, farm input applications, and health and educational attainments.
    Schlagwort(e): O13 - Agriculture ; Natural Resources ; Energy ; Environment ; Other Primary Products, O17 - Formal and Informal Sectors ; Shadow Economy ; Institutional Arrangements, Q12 - Micro Analysis of Farm Firms, Farm Households, and Farm Input Markets, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 2040-5790
    Digitale ISSN: 2040-5804
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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    Consumer Response to "Contains" and "Free of" Labeling: Evidence from Lab Experiments (2013)
    Oxford University Press
    Details
    Publikationsdatum: 2013-11-22
    Beschreibung: Using a lab experiment with 351 adult non-student subjects, we investigate the impact of labels and secondary information on willingness to pay (WTP) for foods that use various ingredients and processes that have been the subject of food policy discussions. We find a distinct asymmetry of WTP sensitivity between "Contains X" and "Free of X" labels with negatively-framed secondary information. The "Free of X" label has an impact only when secondary information is provided, and the negative impact of "Contains X" is mitigated by secondary information. We also consider how the results of our study can inform the ongoing debate about mandatory food labeling regulations in the United States: if mandatory labeling is adopted, providing additional information about what the product contains would significantly lessen the negative impact on demand.
    Schlagwort(e): M31 - Marketing, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 2040-5790
    Digitale ISSN: 2040-5804
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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    Road Block to Risk Management -- Investigating Class I Milk Cross-Hedging Opportunities (2013)
    Oxford University Press
    Details
    Publikationsdatum: 2013-11-22
    Beschreibung: This study examines the risk management opportunities for fluid milk market participants in the United States through the use of milk futures contracts. We estimate the nature of basis risk from 2002–2011 using modern time-series and econometric techniques. The results of this investigation reveal that at sufficient hedging intervals, using class III manufacturing milk futures contracts to cross-hedge fluid milk has the ability to reduce risk and provide revenue stability to market participants. When used in conjunction with milk futures, prediction algorithms for the closing basis facilitate more direct management of fluid milk price risk.
    Schlagwort(e): Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness, Q14 - Agricultural Finance, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 2040-5790
    Digitale ISSN: 2040-5804
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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    Tails Curtailed: Accounting for Nonlinear Dependence in Pricing Margin Insurance for Dairy Farmers (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-07-23
    Beschreibung: Livestock Gross Margin Insurance for Dairy Cattle (LGM-Dairy) is a risk management tool for protecting milk income over feed cost margins. In this article, we examine the assumptions underpinning the method used to determine LGM-Dairy premiums. Analysis of the milk–feed dependence structure is conducted using copula methods, a rich set of tools that allow modelers to capture nonlinearities in dependence among variables of interest. We find a significant relationship between milk and feed prices that increases with time-to-maturity and severity of negative price shocks. Extremal, or tail, dependence is the propensity of dependence to concentrate in the tails of a distribution. A common theme in financial and actuarial applications and in agricultural crop revenue insurance is that tail dependence increases the risk to the underwriter and results in higher insurance premiums. We present, to our knowledge, the first case in which tail dependence may actually reduce actuarially fair premiums for an agricultural risk insurance product. We examine hedging effectiveness with LGM-Dairy and show that, even in the absence of basis or production risk, hedging horizon plays an important role in the ability of this tool to smooth farm income over feed cost margins over time. Rating methodology that accounts for tail dependence between milk and feed prices extends the optimal hedging horizon and increases hedging effectiveness of the LGM-Dairy program.
    Schlagwort(e): G13 - Contingent Pricing ; Futures Pricing, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0002-9092
    Digitale ISSN: 1467-8276
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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    Impact of Third-party Contract Enforcement in Agricultural Markets--A Field Experiment in Vietnam (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-07-23
    Beschreibung: We study the effect of alleviating the information asymmetry regarding product quality that is widespread in contracts between agricultural producers and buyers in developing countries. Opportunistic buyers may underreport quality levels to farmers to reduce the price that they have to pay. In response, farmers may curb investment, thereby negatively affecting farm productivity. In an experiment, we entitle randomly selected smallholder dairy farmers in Vietnam, who are contracted by a large company, to independently verify milk testing results. Results indicate that treatment farmers use 12% more inputs, and they also increase their output significantly. Some wider research and policy implications are discussed.
    Schlagwort(e): C93 - Field Experiments, D82 - Asymmetric and Private Information, O13 - Agriculture ; Natural Resources ; Energy ; Environment ; Other Primary Products, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 0002-9092
    Digitale ISSN: 1467-8276
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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    Strength of Protection for Geographical Indications: Promotion Incentives and Welfare Effects (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-07-23
    Beschreibung: We address the question of how the strength of protection for geographical indications (GIs) affects the GI industry's promotion incentives, equilibrium market outcomes, and the distribution of welfare. Geographical indication producers engage in informative advertising by associating their true quality premium (relative to a substitute product) with a specific label emphasizing the GI's geographic origin. The extent to which the names/words of the GI label can be used and/or imitated by competing products—which depends on the strength of GI protection—determines how informative the GI promotion messages can be. Consumers’ heterogeneous preferences (vis-à-vis the GI quality premium) are modeled in a vertically differentiated framework. Both the GI industry and the substitute product industry are assumed to be competitive (with free entry). The model is calibrated and solved for alternative parameter values. Results show that producers of the GI and of the lower-quality substitute good have divergent interests: GI producers are better off with full protection, whereas the substitute good's producers prefer intermediate levels of protection (but they never prefer zero protection because they benefit indirectly if the GI producers’ incentives to promote are preserved). For consumers and aggregate welfare, the preferred level of protection depends on the model's parameters, with an intermediate level of protection being optimal in many circumstances.
    Schlagwort(e): D23 - Organizational Behavior ; Transaction Costs ; Property Rights, L15 - Information and Product Quality ; Standardization and Compatibility, M37 - Advertising, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 0002-9092
    Digitale ISSN: 1467-8276
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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  • 73
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    Pass-Through and Consumer Search: An Empirical Analysis (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-07-23
    Beschreibung: Retail-price pass-through is one of the most important issues facing manufacturers of consumer packaged goods. Although retailers tend to pass higher wholesale prices through to consumers quickly and completely, they often do not pass on trade promotions. Currently, asymmetric pass-through is commonly thought to result from retailers’ exercise of market power. Alternatively, it may be because of consumer search behavior and retailers’ competitive response. We test this theory using a panel threshold asymmetric error-correction model applied to wholesale and retail scanner data for ready-to-eat cereal for a number of retailers in the Los Angeles metropolitan market. We find that consumer search behavior contributes significantly to imperfect pass-through. By allowing pass-through to depend on market power and consumer search costs, we find results that are contrary to the conventional wisdom. Namely, market power causes retail prices to fall quickly and rise slowly, whereas consumer search behavior causes retail prices to rise quickly and fall slowly—precisely the "rockets and feathers" phenomenon.
    Schlagwort(e): C35 - Discrete Regression and Qualitative Choice Models, L13 - Oligopoly and Other Imperfect Markets, L66 - Food ; Beverages ; Cosmetics ; Tobacco ; Wine and Spirits, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 0002-9092
    Digitale ISSN: 1467-8276
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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  • 74
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    Measuring Benefits from a Marketing Cooperative in the Copper River Fishery (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-07-23
    Beschreibung: The degradation of product quality is one form of rent dissipation resulting from incomplete property rights in fisheries. Industry structure and information asymmetries can also lead to underinvestment in product quality, even when property rights are well defined. In this article we empirically examine whether the voluntary formation of a marketing cooperative was able to mitigate market failures that led to the production of inferior-quality fish. Specifically, we use a difference-in-differences estimation strategy to measure the impact that the Copper River Fishermen's Cooperative, an Alaskan salmon marketing cooperative, had on ex-vessel salmon prices and salmon quality measures. We find that the cooperative was able to improve product quality, as well as attract and sustain a higher price for its salmon. Our findings provide empirical support for many of the key tenets of cooperative theory. Specifically, we find evidence that marketing cooperatives can address existing market failures, that marketing cooperatives can have advantages in high-quality product markets, and that over time, as a result of their success, marketing cooperatives may lead to lasting producer benefits even though they become obsolete due to nonmember free-riding.
    Schlagwort(e): Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness, Q22 - Fishery ; Aquaculture
    Print ISSN: 0002-9092
    Digitale ISSN: 1467-8276
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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    Does Organic Command a Premium When the Food is Already Local? (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-07-23
    Beschreibung: The emergence of community supported agriculture (CSA) farms has been recognized as a new way for small farms to remain competitive while engaging in their local community through direct marketing. In this study, we report on first revealed preference valuation of CSA attributes using data on share prices and CSA characteristics for the summer 2012 growing season. Using data covering 453 CSA farms in Michigan, New York, Ohio, and Pennsylvania, we develop a hedonic model based on firm-level prices to reveal consumer valuations of CSA attributes, including various types of organic certification. We also test for competition in the CSA market using a model of firm entry to evaluate whether firms appear perfectly competitive, which is a requirement when using firm-level prices in our hedonic analysis. Our results reveal a price premium of approximately 7% for USDA organic certification, although this value is heterogeneous across states. We find no premium associated with competing certified naturally grown programs. Finally, we find that CSA farms exhibit little market power and appear to act competitively even with few market entrants.
    Schlagwort(e): Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness, Q51 - Valuation of Environmental Effects
    Print ISSN: 0002-9092
    Digitale ISSN: 1467-8276
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
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    ChIP-Enrich: gene set enrichment testing for ChIP-seq data (2014)
    Oxford University Press
    Details
    Publikationsdatum: 2014-08-01
    Beschreibung: Gene set enrichment testing can enhance the biological interpretation of ChIP-seq data. Here, we develop a method, ChIP-Enrich, for this analysis which empirically adjusts for gene locus length (the length of the gene body and its surrounding non-coding sequence). Adjustment for gene locus length is necessary because it is often positively associated with the presence of one or more peaks and because many biologically defined gene sets have an excess of genes with longer or shorter gene locus lengths. Unlike alternative methods, ChIP-Enrich can account for the wide range of gene locus length-to-peak presence relationships (observed in ENCODE ChIP-seq data sets). We show that ChIP-Enrich has a well-calibrated type I error rate using permuted ENCODE ChIP-seq data sets; in contrast, two commonly used gene set enrichment methods, Fisher's exact test and the binomial test implemented in Genomic Regions Enrichment of Annotations Tool (GREAT), can have highly inflated type I error rates and biases in ranking. We identify DNA-binding proteins, including CTCF, JunD and glucocorticoid receptor α (GRα), that show different enrichment patterns for peaks closer to versus further from transcription start sites. We also identify known and potential new biological functions of GRα. ChIP-Enrich is available as a web interface ( http://chip-enrich.med.umich.edu ) and Bioconductor package.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
    Publiziert von Oxford University Press
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    Will geographical indications supply excessive quality? (2012)
    Oxford University Press
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    Publikationsdatum: 2012-08-03
    Beschreibung: This study investigates the choice of quality by producer organisations (POs) in charge of defining product specifications for geographical indications. The model assumes that the PO chooses the quality level that maximises joint producer profits in anticipation of the competitive equilibrium that arises once quality is set. Using a fairly general variant of the vertical differentiation model and a flexible specification of production costs, we show that the PO has an incentive to supply quality in excess of the socially optimal level.
    Schlagwort(e): L15 - Information and Product Quality ; Standardization and Compatibility, L44 - Antitrust Policy and Public Enterprises, Nonprofit Institutions, and Professional Organization, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 0165-1587
    Digitale ISSN: 1464-3618
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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    Identifying protein interaction subnetworks by a bagging Markov random field-based method (2013)
    Oxford University Press
    Details
    Publikationsdatum: 2013-01-20
    Beschreibung: Identification of differentially expressed subnetworks from protein–protein interaction (PPI) networks has become increasingly important to our global understanding of the molecular mechanisms that drive cancer. Several methods have been proposed for PPI subnetwork identification, but the dependency among network member genes is not explicitly considered, leaving many important hub genes largely unidentified. We present a new method, based on a bagging Markov random field (BMRF) framework, to improve subnetwork identification for mechanistic studies of breast cancer. The method follows a maximum a posteriori principle to form a novel network score that explicitly considers pairwise gene interactions in PPI networks, and it searches for subnetworks with maximal network scores. To improve their robustness across data sets, a bagging scheme based on bootstrapping samples is implemented to statistically select high confidence subnetworks. We first compared the BMRF-based method with existing methods on simulation data to demonstrate its improved performance. We then applied our method to breast cancer data to identify PPI subnetworks associated with breast cancer progression and/or tamoxifen resistance. The experimental results show that not only an improved prediction performance can be achieved by the BMRF approach when tested on independent data sets, but biologically meaningful subnetworks can also be revealed that are relevant to breast cancer and tamoxifen resistance.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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    miRDeep*: an integrated application tool for miRNA identification from RNA sequencing data (2013)
    Oxford University Press
    Details
    Publikationsdatum: 2013-01-20
    Beschreibung: miRDeep and its varieties are widely used to quantify known and novel micro RNA (miRNA) from small RNA sequencing (RNAseq). This article describes miRDeep*, our integrated miRNA identification tool, which is modeled off miRDeep, but the precision of detecting novel miRNAs is improved by introducing new strategies to identify precursor miRNAs. miRDeep* has a user-friendly graphic interface and accepts raw data in FastQ and Sequence Alignment Map (SAM) or the binary equivalent (BAM) format. Known and novel miRNA expression levels, as measured by the number of reads, are displayed in an interface, which shows each RNAseq read relative to the pre-miRNA hairpin. The secondary pre-miRNA structure and read locations for each predicted miRNA are shown and kept in a separate figure file. Moreover, the target genes of known and novel miRNAs are predicted using the TargetScan algorithm, and the targets are ranked according to the confidence score. miRDeep* is an integrated standalone application where sequence alignment, pre-miRNA secondary structure calculation and graphical display are purely Java coded. This application tool can be executed using a normal personal computer with 1.5 GB of memory. Further, we show that miRDeep* outperformed existing miRNA prediction tools using our LNCaP and other small RNAseq datasets. miRDeep* is freely available online at http://www.australianprostatecentre.org/research/software/mirdeep-star .
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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    Aly and THO are required for assembly of the human TREX complex and association of TREX components with the spliced mRNA (2013)
    Oxford University Press
    Details
    Publikationsdatum: 2013-01-20
    Beschreibung: The mRNA export complex TREX (TREX) is known to contain Aly, UAP56, Tex1 and the THO complex, among which UAP56 is required for TREX assembly. Here, we systematically investigated the role of each human TREX component in TREX assembly and its association with the mRNA. We found that Tex1 is essentially a subunit of the THO complex. Aly, THO and UAP56 are all required for assembly of TREX, in which Aly directly interacts with THO subunits Thoc2 and Thoc5. Both Aly and THO function in linking UAP56 to the cap-binding protein CBP80. Interestingly, association of UAP56 with the spliced mRNA, but not with the pre-mRNA, requires Aly and THO. Unexpectedly, we found that Aly and THO require each other to associate with the spliced mRNA. Consistent with these biochemical results, similar to Aly and UAP56, THO plays critical roles in mRNA export. Together, we propose that Aly, THO and UAP56 form a highly integrated unit to associate with the spliced mRNA and function in mRNA export.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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    Analyzing large biological datasets with association networks (2012)
    Oxford University Press
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    Publikationsdatum: 2012-09-27
    Beschreibung: Due to advances in high-throughput biotechnologies biological information is being collected in databases at an amazing rate, requiring novel computational approaches that process collected data into new knowledge in a timely manner. In this study, we propose a computational framework for discovering modular structure, relationships and regularities in complex data. The framework utilizes a semantic-preserving vocabulary to convert records of biological annotations of an object, such as an organism, gene, chemical or sequence, into networks (Anets) of the associated annotations. An association between a pair of annotations in an Anet is determined by the similarity of their co-occurrence pattern with all other annotations in the data. This feature captures associations between annotations that do not necessarily co-occur with each other and facilitates discovery of the most significant relationships in the collected data through clustering and visualization of the Anet. To demonstrate this approach, we applied the framework to the analysis of metadata from the Genomes OnLine Database and produced a biological map of sequenced prokaryotic organisms with three major clusters of metadata that represent pathogens, environmental isolates and plant symbionts.
    Schlagwort(e): Computational Methods, Genomics
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    Integrative analysis of gene and miRNA expression profiles with transcription factor-miRNA feed-forward loops identifies regulators in human cancers (2012)
    Oxford University Press
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    Publikationsdatum: 2012-09-27
    Beschreibung: We describe here a novel method for integrating gene and miRNA expression profiles in cancer using feed-forward loops (FFLs) consisting of transcription factors (TFs), miRNAs and their common target genes. The dChip-GemiNI (Gene and miRNA Network-based Integration) method statistically ranks computationally predicted FFLs by their explanatory power to account for differential gene and miRNA expression between two biological conditions such as normal and cancer. GemiNI integrates not only gene and miRNA expression data but also computationally derived information about TF–target gene and miRNA–mRNA interactions. Literature validation shows that the integrated modeling of expression data and FFLs better identifies cancer-related TFs and miRNAs compared to existing approaches. We have utilized GemiNI for analyzing six data sets of solid cancers (liver, kidney, prostate, lung and germ cell) and found that top-ranked FFLs account for ~20% of transcriptome changes between normal and cancer. We have identified common FFL regulators across multiple cancer types, such as known FFLs consisting of MYC and miR-15/miR-17 families, and novel FFLs consisting of ARNT, CREB1 and their miRNA partners. The results and analysis web server are available at http://www.canevolve.org/dChip-GemiNi .
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Thema: Biologie
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  • 83
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    Discovery of multi-dimensional modules by integrative analysis of cancer genomic data (2012)
    Oxford University Press
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    Publikationsdatum: 2012-10-24
    Beschreibung: Recent technology has made it possible to simultaneously perform multi-platform genomic profiling (e.g. DNA methylation (DM) and gene expression (GE)) of biological samples, resulting in so-called ‘multi-dimensional genomic data’. Such data provide unique opportunities to study the coordination between regulatory mechanisms on multiple levels. However, integrative analysis of multi-dimensional genomics data for the discovery of combinatorial patterns is currently lacking. Here, we adopt a joint matrix factorization technique to address this challenge. This method projects multiple types of genomic data onto a common coordinate system, in which heterogeneous variables weighted highly in the same projected direction form a multi-dimensional module (md-module). Genomic variables in such modules are characterized by significant correlations and likely functional associations. We applied this method to the DM, GE, and microRNA expression data of 385 ovarian cancer samples from the The Cancer Genome Atlas project. These md-modules revealed perturbed pathways that would have been overlooked with only a single type of data, uncovered associations between different layers of cellular activities and allowed the identification of clinically distinct patient subgroups. Our study provides an useful protocol for uncovering hidden patterns and their biological implications in multi-dimensional ‘omic’ data.
    Schlagwort(e): Computational Methods, Genomics
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    Thema: Biologie
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    Detection of dispersed short tandem repeats using reversible jump Markov chain Monte Carlo (2012)
    Oxford University Press
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    Publikationsdatum: 2012-10-24
    Beschreibung: Tandem repeats occur frequently in biological sequences. They are important for studying genome evolution and human disease. A number of methods have been designed to detect a single tandem repeat in a sliding window. In this article, we focus on the case that an unknown number of tandem repeat segments of the same pattern are dispersively distributed in a sequence. We construct a probabilistic generative model for the tandem repeats, where the sequence pattern is represented by a motif matrix. A Bayesian approach is adopted to compute this model. Markov chain Monte Carlo (MCMC) algorithms are used to explore the posterior distribution as an effort to infer both the motif matrix of tandem repeats and the location of repeat segments. Reversible jump Markov chain Monte Carlo (RJMCMC) algorithms are used to address the transdimensional model selection problem raised by the variable number of repeat segments. Experiments on both synthetic data and real data show that this new approach is powerful in detecting dispersed short tandem repeats. As far as we know, it is the first work to adopt RJMCMC algorithms in the detection of tandem repeats.
    Schlagwort(e): Computational Methods, Genomics
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    Thema: Biologie
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  • 85
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    Discovering the hidden sub-network component in a ranked list of genes or proteins derived from genomic experiments (2012)
    Oxford University Press
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    Publikationsdatum: 2012-11-04
    Beschreibung: Genomic experiments (e.g. differential gene expression, single-nucleotide polymorphism association) typically produce ranked list of genes. We present a simple but powerful approach which uses protein–protein interaction data to detect sub-networks within such ranked lists of genes or proteins. We performed an exhaustive study of network parameters that allowed us concluding that the average number of components and the average number of nodes per component are the parameters that best discriminate between real and random networks. A novel aspect that increases the efficiency of this strategy in finding sub-networks is that, in addition to direct connections, also connections mediated by intermediate nodes are considered to build up the sub-networks. The possibility of using of such intermediate nodes makes this approach more robust to noise. It also overcomes some limitations intrinsic to experimental designs based on differential expression, in which some nodes are invariant across conditions. The proposed approach can also be used for candidate disease-gene prioritization. Here, we demonstrate the usefulness of the approach by means of several case examples that include a differential expression analysis in Fanconi Anemia, a genome-wide association study of bipolar disorder and a genome-scale study of essentiality in cancer genes. An efficient and easy-to-use web interface (available at http://www.babelomics.org ) based on HTML5 technologies is also provided to run the algorithm and represent the network.
    Schlagwort(e): Computational Methods, Genomics
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    MetaVelvet: an extension of Velvet assembler to de novo metagenome assembly from short sequence reads (2012)
    Oxford University Press
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    Publikationsdatum: 2012-11-04
    Beschreibung: An important step in ‘metagenomics’ analysis is the assembly of multiple genomes from mixed sequence reads of multiple species in a microbial community. Most conventional pipelines use a single-genome assembler with carefully optimized parameters. A limitation of a single-genome assembler for de novo metagenome assembly is that sequences of highly abundant species are likely misidentified as repeats in a single genome, resulting in a number of small fragmented scaffolds. We extended a single-genome assembler for short reads, known as ‘Velvet’, to metagenome assembly, which we called ‘MetaVelvet’, for mixed short reads of multiple species. Our fundamental concept was to first decompose a de Bruijn graph constructed from mixed short reads into individual sub-graphs, and second, to build scaffolds based on each decomposed de Bruijn sub-graph as an isolate species genome. We made use of two features, the coverage (abundance) difference and graph connectivity, for the decomposition of the de Bruijn graph. For simulated datasets, MetaVelvet succeeded in generating significantly higher N50 scores than any single-genome assemblers. MetaVelvet also reconstructed relatively low-coverage genome sequences as scaffolds. On real datasets of human gut microbial read data, MetaVelvet produced longer scaffolds and increased the number of predicted genes.
    Schlagwort(e): Computational Methods, Genomics
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    Repeat or not repeat?--Statistical validation of tandem repeat prediction in genomic sequences (2012)
    Oxford University Press
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    Publikationsdatum: 2012-11-04
    Beschreibung: Tandem repeats (TRs) represent one of the most prevalent features of genomic sequences. Due to their abundance and functional significance, a plethora of detection tools has been devised over the last two decades. Despite the longstanding interest, TR detection is still not resolved. Our large-scale tests reveal that current detectors produce different, often nonoverlapping inferences, reflecting characteristics of the underlying algorithms rather than the true distribution of TRs in genomic data. Our simulations show that the power of detecting TRs depends on the degree of their divergence, and repeat characteristics such as the length of the minimal repeat unit and their number in tandem. To reconcile the diverse predictions of current algorithms, we propose and evaluate several statistical criteria for measuring the quality of predicted repeat units. In particular, we propose a model-based phylogenetic classifier, entailing a maximum-likelihood estimation of the repeat divergence. Applied in conjunction with the state of the art detectors, our statistical classification scheme for inferred repeats allows to filter out false-positive predictions. Since different algorithms appear to specialize at predicting TRs with certain properties, we advise applying multiple detectors with subsequent filtering to obtain the most complete set of genuine repeats.
    Schlagwort(e): Computational Methods, Genomics
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  • 88
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    Context-specific microRNA analysis: identification of functional microRNAs and their mRNA targets (2012)
    Oxford University Press
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    Publikationsdatum: 2012-11-25
    Beschreibung: MicroRNAs (miRs) function primarily as post-transcriptional negative regulators of gene expression through binding to their mRNA targets. Reliable prediction of a miR’s targets is a considerable bioinformatic challenge of great importance for inferring the miR’s function. Sequence-based prediction algorithms have high false-positive rates, are not in agreement, and are not biological context specific. Here we introduce CoSMic (Context-Specific MicroRNA analysis), an algorithm that combines sequence-based prediction with miR and mRNA expression data. CoSMic differs from existing methods—it identifies miRs that play active roles in the specific biological system of interest and predicts with less false positives their functional targets. We applied CoSMic to search for miRs that regulate the migratory response of human mammary cells to epidermal growth factor (EGF) stimulation. Several such miRs, whose putative targets were significantly enriched by migration processes were identified. We tested three of these miRs experimentally, and showed that they indeed affected the migratory phenotype; we also tested three negative controls. In comparison to other algorithms CoSMic indeed filters out false positives and allows improved identification of context-specific targets. CoSMic can greatly facilitate miR research in general and, in particular, advance our understanding of individual miRs’ function in a specific context.
    Schlagwort(e): Computational Methods, Genomics
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    Who are consuming food away from home and where? Results from the Consumer Expenditure Surveys (2012)
    Oxford University Press
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    Publikationsdatum: 2012-12-28
    Beschreibung: This paper investigates household expenditures on food away from home by type of facility. A system of expenditures at full-service restaurants, fast-food restaurants and other facilities are estimated with a multivariate sample selection procedure, for three types of households by household composition. Statistical significance of error correlations suggests endogeneity of sample selectivity and justifies estimation of the equations in a system to improve statistical efficiency. Differentiated effects of economic and demographic factors are found on expenditures at different facilities and across household types. Findings on the roles of economic and socio-demographic factors can inform marketing strategies and policy deliberations.
    Schlagwort(e): C31 - Cross-Sectional Models ; Spatial Models ; Treatment Effect Models, D12 - Consumer Economics: Empirical Analysis, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 0165-1587
    Digitale ISSN: 1464-3618
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Wirtschaftswissenschaften
    Publiziert von Oxford University Press
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    GBSA: a comprehensive software for analysing whole genome bisulfite sequencing data (2013)
    Oxford University Press
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    Publikationsdatum: 2013-02-20
    Beschreibung: High-throughput sequencing is increasingly being used in combination with bisulfite (BS) assays to study DNA methylation at nucleotide resolution. Although several programmes provide genome-wide alignment of BS-treated reads, the resulting information is not readily interpretable and often requires further bioinformatic steps for meaningful analysis. Current post-alignment BS-sequencing programmes are generally focused on the gene-specific level, a restrictive feature when analysis in the non-coding regions, such as enhancers and intergenic microRNAs, is required. Here, we present Genome Bisulfite Sequencing Analyser (GBSA— http://ctrad-csi.nus.edu.sg/gbsa ), a free open-source software capable of analysing whole-genome bisulfite sequencing data with either a gene-centric or gene-independent focus. Through analysis of the largest published data sets to date, we demonstrate GBSA’s features in providing sequencing quality assessment, methylation scoring, functional data management and visualization of genomic methylation at nucleotide resolution. Additionally, we show that GBSA’s output can be easily integrated with other high-throughput sequencing data, such as RNA-Seq or ChIP-seq, to elucidate the role of methylated intergenic regions in gene regulation. In essence, GBSA allows an investigator to explore not only known loci but also all the genomic regions, for which methylation studies could lead to the discovery of new regulatory mechanisms.
    Schlagwort(e): Computational Methods, Genomics
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    ellipsoidFN: a tool for identifying a heterogeneous set of cancer biomarkers based on gene expressions (2013)
    Oxford University Press
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    Publikationsdatum: 2013-02-20
    Beschreibung: Computationally identifying effective biomarkers for cancers from gene expression profiles is an important and challenging task. The challenge lies in the complicated pathogenesis of cancers that often involve the dysfunction of many genes and regulatory interactions. Thus, sophisticated classification model is in pressing need. In this study, we proposed an efficient approach, called ellipsoidFN (ellipsoid Feature Net), to model the disease complexity by ellipsoids and seek a set of heterogeneous biomarkers. Our approach achieves a non-linear classification scheme for the mixed samples by the ellipsoid concept, and at the same time uses a linear programming framework to efficiently select biomarkers from high-dimensional space. ellipsoidFN reduces the redundancy and improves the complementariness between the identified biomarkers, thus significantly enhancing the distinctiveness between cancers and normal samples, and even between cancer types. Numerical evaluation on real prostate cancer, breast cancer and leukemia gene expression datasets suggested that ellipsoidFN outperforms the state-of-the-art biomarker identification methods, and it can serve as a useful tool for cancer biomarker identification in the future. The Matlab code of ellipsoidFN is freely available from http://doc.aporc.org/wiki/EllipsoidFN .
    Schlagwort(e): Computational Methods, Genomics
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    Volatility in mRNA secondary structure as a design principle for antisense (2013)
    Oxford University Press
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    Publikationsdatum: 2013-02-02
    Beschreibung: Designing effective antisense sequences is a formidable problem. A method for predicting efficacious antisense holds the potential to provide fundamental insight into this biophysical process. More practically, such an understanding increases the chance of successful antisense design as well as saving considerable time, money and labor. The secondary structure of an mRNA molecule is believed to be in a constant state of flux, sampling several different suboptimal states. We hypothesized that particularly volatile regions might provide better accessibility for antisense targeting. A computational framework, GenAVERT was developed to evaluate this hypothesis. GenAVERT used UNAFold and RNAforester to generate and compare the predicted suboptimal structures of mRNA sequences. Subsequent analysis revealed regions that were particularly volatile in terms of intramolecular hydrogen bonding, and thus potentially superior antisense targets due to their high accessibility. Several mRNA sequences with known natural antisense target sites as well as artificial antisense target sites were evaluated. Upon comparison, antisense sequences predicted based upon the volatility hypothesis closely matched those of the naturally occurring antisense, as well as those artificial target sites that provided efficient down-regulation. These results suggest that this strategy may provide a powerful new approach to antisense design.
    Schlagwort(e): Computational Methods, Genomics
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    EMdeCODE: a novel algorithm capable of reading words of epigenetic code to predict enhancers and retroviral integration sites and to identify H3R2me1 as a distinctive mark of coding versus non-coding genes (2013)
    Oxford University Press
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    Publikationsdatum: 2013-02-02
    Beschreibung: Existence of some extra-genetic (epigenetic) codes has been postulated since the discovery of the primary genetic code. Evident effects of histone post-translational modifications or DNA methylation over the efficiency and the regulation of DNA processes are supporting this postulation. EMdeCODE is an original algorithm that approximate the genomic distribution of given DNA features (e.g. promoter, enhancer, viral integration) by identifying relevant ChIPSeq profiles of post-translational histone marks or DNA binding proteins and combining them in a supermark. EMdeCODE kernel is essentially a two-step procedure: (i) an expectation-maximization process calculates the mixture of epigenetic factors that maximize the Sensitivity (recall) of the association with the feature under study; (ii) the approximated density is then recursively trimmed with respect to a control dataset to increase the precision by reducing the number of false positives. EMdeCODE densities improve significantly the prediction of enhancer loci and retroviral integration sites with respect to previous methods. Importantly, it can also be used to extract distinctive factors between two arbitrary conditions. Indeed EMdeCODE identifies unexpected epigenetic profiles specific for coding versus non-coding RNA, pointing towards a new role for H3R2me1 in coding regions.
    Schlagwort(e): Computational Methods, Genomics
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    A population model for genotyping indels from next-generation sequence data (2013)
    Oxford University Press
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    Publikationsdatum: 2013-02-02
    Beschreibung: Insertion and deletion polymorphisms (indels) are an important source of genomic variation in plant and animal genomes, but accurate genotyping from low-coverage and exome next-generation sequence data remains challenging. We introduce an efficient population clustering algorithm for diploids and polyploids which was tested on a dataset of 2000 exomes. Compared with existing methods, we report a 4-fold reduction in overall indel genotype error rates with a 9-fold reduction in low coverage regions.
    Schlagwort(e): Computational Methods, Genomics
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    PreCisIon: PREdiction of CIS-regulatory elements improved by gene's positION (2013)
    Oxford University Press
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    Publikationsdatum: 2013-02-02
    Beschreibung: Conventional approaches to predict transcriptional regulatory interactions usually rely on the definition of a shared motif sequence on the target genes of a transcription factor (TF). These efforts have been frustrated by the limited availability and accuracy of TF binding site motifs, usually represented as position-specific scoring matrices, which may match large numbers of sites and produce an unreliable list of target genes. To improve the prediction of binding sites, we propose to additionally use the unrelated knowledge of the genome layout. Indeed, it has been shown that co-regulated genes tend to be either neighbors or periodically spaced along the whole chromosome. This study demonstrates that respective gene positioning carries significant information. This novel type of information is combined with traditional sequence information by a machine learning algorithm called PreCisIon. To optimize this combination, PreCisIon builds a strong gene target classifier by adaptively combining weak classifiers based on either local binding sequence or global gene position. This strategy generically paves the way to the optimized incorporation of any future advances in gene target prediction based on local sequence, genome layout or on novel criteria. With the current state of the art, PreCisIon consistently improves methods based on sequence information only. This is shown by implementing a cross-validation analysis of the 20 major TFs from two phylogenetically remote model organisms. For Bacillus subtilis and Escherichia coli , respectively, PreCisIon achieves on average an area under the receiver operating characteristic curve of 70 and 60%, a sensitivity of 80 and 70% and a specificity of 60 and 56%. The newly predicted gene targets are demonstrated to be functionally consistent with previously known targets, as assessed by analysis of Gene Ontology enrichment or of the relevant literature and databases.
    Schlagwort(e): Computational Methods, Genomics
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    miRNA target enrichment analysis reveals directly active miRNAs in health and disease (2013)
    Oxford University Press
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    Publikationsdatum: 2013-02-02
    Beschreibung: microRNAs (miRNAs) are short non-coding regulatory RNA molecules. The activity of a miRNA in a biological process can often be reflected in the expression program that characterizes the outcome of the activity. We introduce a computational approach that infers such activity from high-throughput data using a novel statistical methodology, called minimum-mHG (mmHG), that examines mutual enrichment in two ranked lists. Based on this methodology, we provide a user-friendly web application that supports the statistical assessment of miRNA target enrichment analysis (miTEA) in the top of a ranked list of genes or proteins. Using miTEA, we analyze several target prediction tools by examining performance on public miRNA constitutive expression data. We also apply miTEA to analyze several integrative biology data sets, including a novel matched miRNA/mRNA data set covering nine human tissue types. Our novel findings include proposed direct activity of miR-519 in placenta, a direct activity of the oncogenic miR-15 in different healthy tissue types and a direct activity of the poorly characterized miR-768 in both healthy tissue types and cancer cell lines. The miTEA web application is available at http://cbl-gorilla.cs.technion.ac.il/miTEA/ .
    Schlagwort(e): Computational Methods, Genomics
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    The twilight zone of cis element alignments (2013)
    Oxford University Press
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    Publikationsdatum: 2013-02-02
    Beschreibung: Sequence alignment of proteins and nucleic acids is a routine task in bioinformatics. Although the comparison of complete peptides, genes or genomes can be undertaken with a great variety of tools, the alignment of short DNA sequences and motifs entails pitfalls that have not been fully addressed yet. Here we confront the structural superposition of transcription factors with the sequence alignment of their recognized cis elements. Our goals are (i) to test TFcompare ( http://floresta.eead.csic.es/tfcompare ), a structural alignment method for protein–DNA complexes; (ii) to benchmark the pairwise alignment of regulatory elements; (iii) to define the confidence limits and the twilight zone of such alignments and (iv) to evaluate the relevance of these thresholds with elements obtained experimentally. We find that the structure of cis elements and protein–DNA interfaces is significantly more conserved than their sequence and measures how this correlates with alignment errors when only sequence information is considered. Our results confirm that DNA motifs in the form of matrices produce better alignments than individual sequences. Finally, we report that empirical and theoretically derived twilight thresholds are useful for estimating the natural plasticity of regulatory sequences, and hence for filtering out unreliable alignments.
    Schlagwort(e): Computational Methods, Genomics
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    TEAK: Topology Enrichment Analysis frameworK for detecting activated biological subpathways (2013)
    Oxford University Press
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    Publikationsdatum: 2013-02-02
    Beschreibung: To mine gene expression data sets effectively, analysis frameworks need to incorporate methods that identify intergenic relationships within enriched biologically relevant subpathways. For this purpose, we developed the Topology Enrichment Analysis frameworK (TEAK). TEAK employs a novel in-house algorithm and a tailor-made Clique Percolation Method to extract linear and nonlinear KEGG subpathways, respectively. TEAK scores subpathways using the Bayesian Information Criterion for context specific data and the Kullback-Leibler divergence for case–control data. In this article, we utilized TEAK with experimental studies to analyze microarray data sets profiling stress responses in the model eukaryote Saccharomyces cerevisiae . Using a public microarray data set, we identified via TEAK linear sphingolipid metabolic subpathways activated during the yeast response to nitrogen stress, and phenotypic analyses of the corresponding deletion strains indicated previously unreported fitness defects for the dpl1 and lag1 mutants under conditions of nitrogen limitation. In addition, we studied the yeast filamentous response to nitrogen stress by profiling changes in transcript levels upon deletion of two key filamentous growth transcription factors, FLO8 and MSS11 . Via TEAK we identified a nonlinear glycerophospholipid metabolism subpathway involving the SLC1 gene, which we found via mutational analysis to be required for yeast filamentous growth.
    Schlagwort(e): Computational Methods, Genomics
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    Improving detection of copy-number variation by simultaneous bias correction and read-depth segmentation (2013)
    Oxford University Press
    Details
    Publikationsdatum: 2013-02-02
    Beschreibung: Structural variation is an important class of genetic variation in mammals. High-throughput sequencing (HTS) technologies promise to revolutionize copy-number variation (CNV) detection but present substantial analytic challenges. Converging evidence suggests that multiple types of CNV-informative data (e.g. read-depth, read-pair, split-read) need be considered, and that sophisticated methods are needed for more accurate CNV detection. We observed that various sources of experimental biases in HTS confound read-depth estimation, and note that bias correction has not been adequately addressed by existing methods. We present a novel read-depth–based method, GENSENG, which uses a hidden Markov model and negative binomial regression framework to identify regions of discrete copy-number changes while simultaneously accounting for the effects of multiple confounders. Based on extensive calibration using multiple HTS data sets, we conclude that our method outperforms existing read-depth–based CNV detection algorithms. The concept of simultaneous bias correction and CNV detection can serve as a basis for combining read-depth with other types of information such as read-pair or split-read in a single analysis. A user-friendly and computationally efficient implementation of our method is freely available.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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    A scale-space method for detecting recurrent DNA copy number changes with analytical false discovery rate control (2013)
    Oxford University Press
    Details
    Publikationsdatum: 2013-05-04
    Beschreibung: Tumor formation is partially driven by DNA copy number changes, which are typically measured using array comparative genomic hybridization, SNP arrays and DNA sequencing platforms. Many techniques are available for detecting recurring aberrations across multiple tumor samples, including CMAR, STAC, GISTIC and KC-SMART. GISTIC is widely used and detects both broad and focal (potentially overlapping) recurring events. However, GISTIC performs false discovery rate control on probes instead of events. Here we propose Analytical Multi-scale Identification of Recurrent Events, a multi-scale Gaussian smoothing approach, for the detection of both broad and focal (potentially overlapping) recurring copy number alterations. Importantly, false discovery rate control is performed analytically (no need for permutations) on events rather than probes. The method does not require segmentation or calling on the input dataset and therefore reduces the potential loss of information due to discretization. An important characteristic of the approach is that the error rate is controlled across all scales and that the algorithm outputs a single profile of significant events selected from the appropriate scales. We perform extensive simulations and showcase its utility on a glioblastoma SNP array dataset. Importantly, ADMIRE detects focal events that are missed by GISTIC, including two events involving known glioma tumor-suppressor genes: CDKN2C and NF1.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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