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  • Computational Methods, Genomics  (24)
  • Food Policy  (24)
  • Oxford University Press  (48)
  • American Chemical Society
  • American Geophysical Union
  • American Physical Society
  • 2020-2023
  • 2015-2019  (48)
  • 1990-1994
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  • 2015  (48)
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  • Oxford University Press  (48)
  • American Chemical Society
  • American Geophysical Union
  • American Physical Society
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  • 2020-2023
  • 2015-2019  (48)
  • 1990-1994
  • 1985-1989
  • 1975-1979
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  • 1
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    A Wicked Problem? Cost Containment in the Women, Infants and Children Program (2015)
    Oxford University Press
    Details
    Publication Date: 2015-08-11
    Description: The Special Supplemental Nutrition Program for Women, Infants and Children (WIC) Program is a key part of America's safety net, but its structure fails to incentivize participants to be cost-conscious in their purchases and may cause retailers to attach excessive markups to WIC products. We investigate cost containment in the WIC Program, with a focus on California. Results show that smaller vendors often charge considerably higher prices for WIC foods than their larger counterparts. However, larger vendors do not mark up WIC foods more or promote them less than comparable control products. Cost containment can be improved by targeting WIC Program sales to larger vendors when it is possible to do so without compromising participant access, and using large-vendor prices as a benchmark to limit prices set by smaller vendors.
    Keywords: D12 - Consumer Economics: Empirical Analysis, I38 - Government Policy ; Provision and Effects of Welfare Programs, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 2040-5790
    Electronic ISSN: 2040-5804
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
    Published by Oxford University Press
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    A low-latency, big database system and browser for storage, querying and visualization of 3D genomic data (2015)
    Oxford University Press
    Details
    Publication Date: 2015-09-19
    Description: Recent releases of genome three-dimensional (3D) structures have the potential to transform our understanding of genomes. Nonetheless, the storage technology and visualization tools need to evolve to offer to the scientific community fast and convenient access to these data. We introduce simultaneously a database system to store and query 3D genomic data ( 3DBG ), and a 3D genome browser to visualize and explore 3D genome structures ( 3DGB ). We benchmark 3DBG against state-of-the-art systems and demonstrate that it is faster than previous solutions, and importantly gracefully scales with the size of data. We also illustrate the usefulness of our 3D genome Web browser to explore human genome structures. The 3D genome browser is available at http://3dgb.cs.mcgill.ca/ .
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 3
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    Analysis of strand-specific RNA-seq data using machine learning reveals the structures of transcription units in Clostridium thermocellum (2015)
    Oxford University Press
    Details
    Publication Date: 2015-05-29
    Description: Identification of transcription units (TUs) encoded in a bacterial genome is essential to elucidation of transcriptional regulation of the organism. To gain a detailed understanding of the dynamically composed TU structures, we have used four strand-specific RNA-seq (ssRNA-seq) datasets collected under two experimental conditions to derive the genomic TU organization of Clostridium thermocellum using a machine-learning approach. Our method accurately predicted the genomic boundaries of individual TUs based on two sets of parameters measuring the RNA-seq expression patterns across the genome: expression-level continuity and variance. A total of 2590 distinct TUs are predicted based on the four RNA-seq datasets. Among the predicted TUs, 44% have multiple genes. We assessed our prediction method on an independent set of RNA-seq data with longer reads. The evaluation confirmed the high quality of the predicted TUs. Functional enrichment analyses on a selected subset of the predicted TUs revealed interesting biology. To demonstrate the generality of the prediction method, we have also applied the method to RNA-seq data collected on Escherichia coli and achieved high prediction accuracies. The TU prediction program named SeqTU is publicly available at https://code.google.com/p/seqtu/ . We expect that the predicted TUs can serve as the baseline information for studying transcriptional and post-transcriptional regulation in C. thermocellum and other bacteria.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 4
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    A thesaurus of genetic variation for interrogation of repetitive genomic regions (2015)
    Oxford University Press
    Details
    Publication Date: 2015-05-29
    Description: Detecting genetic variation is one of the main applications of high-throughput sequencing, but is still challenging wherever aligning short reads poses ambiguities. Current state-of-the-art variant calling approaches avoid such regions, arguing that it is necessary to sacrifice detection sensitivity to limit false discovery. We developed a method that links candidate variant positions within repetitive genomic regions into clusters. The technique relies on a resource, a thesaurus of genetic variation, that enumerates genomic regions with similar sequence. The resource is computationally intensive to generate, but once compiled can be applied efficiently to annotate and prioritize variants in repetitive regions. We show that thesaurus annotation can reduce the rate of false variant calls due to mappability by up to three orders of magnitude. We apply the technique to whole genome datasets and establish that called variants in low mappability regions annotated using the thesaurus can be experimentally validated. We then extend the analysis to a large panel of exomes to show that the annotation technique opens possibilities to study variation in hereto hidden and under-studied parts of the genome.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 5
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    Simulating welfare effects of the European nutrition and health claims' regulation: the Italian yogurt market (2015)
    Oxford University Press
    Details
    Publication Date: 2015-05-26
    Description: With the enactment of Regulation (EC) No. 1924/2006, 20 December 2006, ‘ On nutrition and health claims made on foods ’ several health claims can no longer be used on food products in European markets. We simulate the overall impact of the regulation on consumers and producers using the Italian yogurt market as a case study, and data prior to the introduction of the policy. We quantify welfare losses incurred if accepted claims were false, and simulate scenarios where rejected truthful health claims are removed, considering also the case where the products carrying them exit the market. We find that consumers can incur large welfare losses if approved claims are untruthful; if truthful claims are instead denied both consumers and producers may incur losses, with consumers being penalised more than producers.
    Keywords: L66 - Food ; Beverages ; Cosmetics ; Tobacco ; Wine and Spirits, M38 - Government Policy and Regulation, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0165-1587
    Electronic ISSN: 1464-3618
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
    Published by Oxford University Press
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  • 6
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    Following the footprints of polymorphic inversions on SNP data: from detection to association tests (2015)
    Oxford University Press
    Details
    Publication Date: 2015-05-03
    Description: Inversion polymorphisms have important phenotypic and evolutionary consequences in humans. Two different methodologies have been used to infer inversions from SNP dense data, enabling the use of large cohorts for their study. One approach relies on the differences in linkage disequilibrium across breakpoints; the other one captures the internal haplotype groups that tag the inversion status of chromosomes. In this article, we assessed the convergence of the two methods in the detection of 20 human inversions that have been reported in the literature. The methods converged in four inversions including inv-8p23, for which we studied its association with low-BMI in American children. Using a novel haplotype tagging method with control on inversion ancestry, we computed the frequency of inv-8p23 in two American cohorts and observed inversion haplotype admixture. Accounting for haplotype ancestry, we found that the European inverted allele in children carries a recessive risk of underweight, validated in an independent Spanish cohort (combined: OR= 2.00, P = 0.001). While the footprints of inversions on SNP data are complex, we show that systematic analyses, such as convergence of different methods and controlling for ancestry, can reveal the contribution of inversions to the ancestral composition of populations and to the heritability of human disease.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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    Reconstructing genome-scale metabolic models with merlin (2015)
    Oxford University Press
    Details
    Publication Date: 2015-05-03
    Description: The Metabolic Models Reconstruction Using Genome-Scale Information ( merlin ) tool is a user-friendly Java application that aids the reconstruction of genome-scale metabolic models for any organism that has its genome sequenced. It performs the major steps of the reconstruction process, including the functional genomic annotation of the whole genome and subsequent construction of the portfolio of reactions. Moreover, merlin includes tools for the identification and annotation of genes encoding transport proteins, generating the transport reactions for those carriers. It also performs the compartmentalisation of the model, predicting the organelle localisation of the proteins encoded in the genome and thus the localisation of the metabolites involved in the reactions promoted by such enzymes. The gene-proteins-reactions (GPR) associations are automatically generated and included in the model. Finally, merlin expedites the transition from genomic data to draft metabolic models reconstructions exported in the SBML standard format, allowing the user to have a preliminary view of the biochemical network, which can be manually curated within the environment provided by merlin .
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 8
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    Inferential modeling of 3D chromatin structure (2015)
    Oxford University Press
    Details
    Publication Date: 2015-05-03
    Description: For eukaryotic cells, the biological processes involving regulatory DNA elements play an important role in cell cycle. Understanding 3D spatial arrangements of chromosomes and revealing long-range chromatin interactions are critical to decipher these biological processes. In recent years, chromosome conformation capture (3C) related techniques have been developed to measure the interaction frequencies between long-range genome loci, which have provided a great opportunity to decode the 3D organization of the genome. In this paper, we develop a new Bayesian framework to derive the 3D architecture of a chromosome from 3C-based data. By modeling each chromosome as a polymer chain, we define the conformational energy based on our current knowledge on polymer physics and use it as prior information in the Bayesian framework. We also propose an expectation-maximization (EM) based algorithm to estimate the unknown parameters of the Bayesian model and infer an ensemble of chromatin structures based on interaction frequency data. We have validated our Bayesian inference approach through cross-validation and verified the computed chromatin conformations using the geometric constraints derived from fluorescence in situ hybridization (FISH) experiments. We have further confirmed the inferred chromatin structures using the known genetic interactions derived from other studies in the literature. Our test results have indicated that our Bayesian framework can compute an accurate ensemble of 3D chromatin conformations that best interpret the distance constraints derived from 3C-based data and also agree with other sources of geometric constraints derived from experimental evidence in the previous studies. The source code of our approach can be found in https://github.com/wangsy11/InfMod3DGen .
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 9
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    Integrating motif, DNA accessibility and gene expression data to build regulatory maps in an organism (2015)
    Oxford University Press
    Details
    Publication Date: 2015-05-03
    Description: Characterization of cell type specific regulatory networks and elements is a major challenge in genomics, and emerging strategies frequently employ high-throughput genome-wide assays of transcription factor (TF) to DNA binding, histone modifications or chromatin state. However, these experiments remain too difficult/expensive for many laboratories to apply comprehensively to their system of interest. Here, we explore the potential of elucidating regulatory systems in varied cell types using computational techniques that rely on only data of gene expression, low-resolution chromatin accessibility, and TF–DNA binding specificities (‘motifs’). We show that static computational motif scans overlaid with chromatin accessibility data reasonably approximate experimentally measured TF–DNA binding. We demonstrate that predicted binding profiles and expression patterns of hundreds of TFs are sufficient to identify major regulators of ~200 spatiotemporal expression domains in the Drosophila embryo. We are then able to learn reliable statistical models of enhancer activity for over 70 expression domains and apply those models to annotate domain specific enhancers genome-wide. Throughout this work, we apply our motif and accessibility based approach to comprehensively characterize the regulatory network of fruitfly embryonic development and show that the accuracy of our computational method compares favorably to approaches that rely on data from many experimental assays.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 10
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    Grain Promotion and Food Consumption: Analysis of Chinese Provincial Data (2015)
    Oxford University Press
    Details
    Publication Date: 2015-05-12
    Description: China has long struggled to achieve food security. In the era of a planned economy, local self-sufficiency was dictated by policy. With China's transition to a market economy, however, different policy schemes have been utilized, with greater emphasis placed on the role of market forces, especially in conjunction with China's accession to the World Trade Organization in 2001. Nevertheless, self-sufficiency in grain production remains a deeply rooted goal, and interventionist measures geared towards its achievement are still viewed as the most direct and effective means of food security. This paper examines how the well-being of China's rural population, proxied by measures of food consumption, is affected by the promotion of grain production. Our findings suggest that targeted households bear a disproportionate burden of food security policy, as it is currently implemented.
    Keywords: O12 - Microeconomic Analyses of Economic Development, Q12 - Micro Analysis of Farm Firms, Farm Households, and Farm Input Markets, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 2040-5790
    Electronic ISSN: 2040-5804
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
    Published by Oxford University Press
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  • 11
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    Measuring Food Access and Food Deserts for Policy Purposes{dagger} (2015)
    Oxford University Press
    Details
    Publication Date: 2015-05-12
    Description: Policymakers have dedicated increasing attention to whether Americans have access to healthful food. As a result, various methods for measuring food store access at the national level have been developed to identify areas that lack access. However, these methods face definitional, data, and methodological limitations. The focus on neighborhoods instead of individuals underestimates the barriers that some individuals face in accessing healthy food, and overestimates the problem in other neighborhoods. This paper reviews and critiques currently available national-level measures of food access. While multiple measures of food access are needed to understand the problem, we recommend greater attention be paid to individual measures of food store access.
    Keywords: I14 - Health and Inequality, I18 - Government Policy ; Regulation ; Public Health, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 2040-5790
    Electronic ISSN: 2040-5804
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
    Published by Oxford University Press
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  • 12
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    Decomposing the Farmer's Share of the Food Dollar (2015)
    Oxford University Press
    Details
    Publication Date: 2015-05-12
    Description: The Canadian farm share for five crop-based products and seven livestock-based products from 1997 to 2010 is calculated using a supply chain IO analysis. Significant differences exist in farm shares across food commodities with higher farm shares for livestock products and lower farm shares for grain-based products. The decline in the Canadian farm share for food consumed at home is driven in large part by the food purchasing habits of consumers. This paper also addresses the hypothesis that the decline in the Canadian farm share could be partially driven by rising input costs in post-farmgate processes or rising input costs that have greater impact on downstream sectors than primary agricultural producers. Three experiments were conducted to assess the impact of an increase in the cost of corn, energy, and farm labor would have on commodity output prices, farm returns, food expenditure, and farm share. In all three cases, the overall farm share increases, albeit by a small amount, suggesting that these shocks have a larger relative impact on the prices of agricultural commodities than the prices of marketing commodities used in post-farmgate activities. A two-period comparison of these simulations shows that energy (corn and farm labour) price shocks would have had a greater (lower) impact on the farm share in 2007 than 1997.
    Keywords: Q11 - Aggregate Supply and Demand Analysis ; Prices, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 2040-5790
    Electronic ISSN: 2040-5804
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
    Published by Oxford University Press
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  • 13
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    Food Insecurity and Food Access in U.S. Metropolitan Areas (2015)
    Oxford University Press
    Details
    Publication Date: 2015-05-12
    Description: Household food insecurity in the United States has reached its highest levels to date. As public and private initiatives have emerged to help improve diets by fostering access to food, the availability of more food stores may result in lower levels of food insecurity. In this article, we assess the relationship between adult food insecurity and food store density in metropolitan areas of the United States. We find that while small grocery/convenience stores show a mitigating effect on adult food insecurity across different samples of households, the effects of large supermarkets/grocery stores and supercenters vary. We also find that Supplemental Nutrition Assistance Program participation and food access can have a simultaneously beneficial effect in reducing adult food insecurity. Implications for policies aiming to improve food security by fostering access to food stores are discussed.
    Keywords: I14 - Health and Inequality, L81 - Retail and Wholesale Trade ; e-Commerce, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 2040-5790
    Electronic ISSN: 2040-5804
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
    Published by Oxford University Press
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  • 14
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    Tariffs and non-tariff frictions in the world wine trade (2015)
    Oxford University Press
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    Publication Date: 2015-12-29
    Description: This article empirically investigates the impact of trade barriers on the world wine trade focusing on trade costs impeding exports, including transport, tariffs, technical barriers and sanitary and phytosanitary (SPS) standards. A gravity model is estimated using data from the main importing and exporting countries for the years 1997–2010. The Poison pseudo-maximum likelihood estimator accounts for heteroskedasticity and the presence of zero trade flows. Our results identify which regulations can adversely affect trade providing useful information to policy-makers involved in negotiations on trade frictions. While SPS measures do not seem to obstruct exports, technical barriers have a varying impact on trade. A decreasing trend for tariffs has largely been compensated by more stringent technical barriers. The overall result is that frictions in the world wine trade have not changed during the past 15 years.
    Keywords: F13 - Trade Policy ; International Trade Organizations, Q17 - Agriculture in International Trade, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0165-1587
    Electronic ISSN: 1464-3618
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
    Published by Oxford University Press
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    A statistical framework for revealing signaling pathways perturbed by DNA variants (2015)
    Oxford University Press
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    Publication Date: 2015-06-24
    Description: Much of the inter-individual variation in gene expression is triggered via perturbations of signaling networks by DNA variants. We present a novel probabilistic approach for identifying the particular pathways by which DNA variants perturb the signaling network. Our procedure, called PINE, relies on a systematic integration of established biological knowledge of signaling networks with data on transcriptional responses to various experimental conditions. Unlike previous approaches, PINE provides statistical aspects that are critical for prioritizing hypotheses for followup experiments. Using simulated data, we show that higher accuracy is attained with PINE than with existing methods. We used PINE to analyze transcriptional responses of immune dendritic cells to several pathogenic stimulations. PINE identified statistically significant genetic perturbations in the pathogen-sensing signaling network, suggesting previously uncharacterized regulatory mechanisms for functional DNA variants.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 16
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    Why weight? Modelling sample and observational level variability improves power in RNA-seq analyses (2015)
    Oxford University Press
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    Publication Date: 2015-08-29
    Description: Variations in sample quality are frequently encountered in small RNA-sequencing experiments, and pose a major challenge in a differential expression analysis. Removal of high variation samples reduces noise, but at a cost of reducing power, thus limiting our ability to detect biologically meaningful changes. Similarly, retaining these samples in the analysis may not reveal any statistically significant changes due to the higher noise level. A compromise is to use all available data, but to down-weight the observations from more variable samples. We describe a statistical approach that facilitates this by modelling heterogeneity at both the sample and observational levels as part of the differential expression analysis. At the sample level this is achieved by fitting a log-linear variance model that includes common sample-specific or group-specific parameters that are shared between genes. The estimated sample variance factors are then converted to weights and combined with observational level weights obtained from the mean–variance relationship of the log-counts-per-million using ‘voom’. A comprehensive analysis involving both simulations and experimental RNA-sequencing data demonstrates that this strategy leads to a universally more powerful analysis and fewer false discoveries when compared to conventional approaches. This methodology has wide application and is implemented in the open-source ‘limma’ package.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 17
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    RAX2: a genome-wide detection method of condition-associated transcription variation (2015)
    Oxford University Press
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    Publication Date: 2015-08-29
    Description: Most mammalian genes have mRNA variants due to alternative promoter usage, alternative splicing, and alternative cleavage and polyadenylation. Expression of alternative RNA isoforms has been found to be associated with tumorigenesis, proliferation and differentiation. Detection of condition-associated transcription variation requires association methods. Traditional association methods such as Pearson chi-square test and Fisher Exact test are single test methods and do not work on count data with replicates. Although the Cochran Mantel Haenszel (CMH) approach can handle replicated count data, our simulations showed that multiple CMH tests still had very low power. To identify condition-associated variation of transcription, we here proposed a ranking analysis of chi-squares (RAX2) for large-scale association analysis. RAX2 is a nonparametric method and has accurate and conservative estimation of FDR profile. Simulations demonstrated that RAX2 performs well in finding condition-associated transcription variants. We applied RAX2 to primary T-cell transcriptomic data and identified 1610 (16.3%) tags associated in transcription with immune stimulation at FDR 〈 0.05. Most of these tags also had differential expression. Analysis of two and three tags within genes revealed that under immune stimulation short RNA isoforms were preferably used.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 18
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    Following Up on Smallholder Farmers and Supermarkets in Kenya (2015)
    Oxford University Press
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    Publication Date: 2015-07-10
    Description: In many developing countries, supermarkets are expanding rapidly. This affects farmers’ marketing options. Previous studies have analyzed welfare effects of smallholder participation in supermarket channels from a static perspective, using cross-section data. We develop a conceptual framework and use panel data to better understand participation and impact dynamics. The analysis focuses on vegetable producers in Kenya. Participation in supermarket channels is associated with income gains. However, many farmers have dropped out of the supermarket channel due to various constraints. The initial income gains cannot be sustained when returning to the traditional market. Organizational support may be needed to avoid widening income disparities.
    Keywords: L24 - Contracting Out ; Joint Ventures ; Technology Licensing, O12 - Microeconomic Analyses of Economic Development, O13 - Agriculture ; Natural Resources ; Energy ; Environment ; Other Primary Products, Q12 - Micro Analysis of Farm Firms, Farm Households, and Farm Input Markets, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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    Diet Quality, Child Health, and Food Policies in Developing Countries (2015)
    Oxford University Press
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    Publication Date: 2015-07-15
    Description: Although the importance of diet quality for improving child health is widely recognized, the roles of environmental factors and the absorption of nutrients for children's physical growth and morbidity have not been adequately integrated into a policy framework. Moreover, nutrient intakes gradually affect child health, so it is helpful to use alternative tools to evaluate short-term interventions versus long-term food policies. This article emphasizes the role of diet quality reflected in the intake of nutrients such as protein, calcium, and iron for children's physical growth. Vitamins A and C are important for reducing morbidity. Children's growth and morbidity affect their cognitive development, which is critical for the future supply of skilled labor and economic growth. Evidence on these issues from countries such as Bangladesh, India, Kenya, the Philippines, and Tanzania is summarized. The supply of nutritious foods is appraised from the viewpoint of improving diet quality. Finally, the roles of educational campaigns and indirect taxes on unhealthy processed foods consumed by the affluent in developing countries are discussed.
    Keywords: O12 - Microeconomic Analyses of Economic Development, I15 - Health and Economic Development, I25 - Education and Economic Development, J10 - General, Q01 - Sustainable Development, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0257-3032
    Electronic ISSN: 1564-6971
    Topics: Economics
    Published by Oxford University Press
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    Unique transposon landscapes are pervasive across Drosophila melanogaster genomes (2015)
    Oxford University Press
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    Publication Date: 2015-12-16
    Description: To understand how transposon landscapes (TLs) vary across animal genomes, we describe a new method called the Transposon Insertion and Depletion AnaLyzer (TIDAL) and a database of 〉300 TLs in Drosophila melanogaster (TIDAL-Fly). Our analysis reveals pervasive TL diversity across cell lines and fly strains, even for identically named sub-strains from different laboratories such as the ISO1 strain used for the reference genome sequence. On average, 〉500 novel insertions exist in every lab strain, inbred strains of the Drosophila Genetic Reference Panel (DGRP), and fly isolates in the Drosophila Genome Nexus (DGN). A minority (〈25%) of transposon families comprise the majority (〉70%) of TL diversity across fly strains. A sharp contrast between insertion and depletion patterns indicates that many transposons are unique to the ISO1 reference genome sequence. Although TL diversity from fly strains reaches asymptotic limits with increasing sequencing depth, rampant TL diversity causes unsaturated detection of TLs in pools of flies. Finally, we show novel transposon insertions negatively correlate with Piwi-interacting RNA (piRNA) levels for most transposon families, except for the highly-abundant roo retrotransposon. Our study provides a useful resource for Drosophila geneticists to understand how transposons create extensive genomic diversity in fly cell lines and strains.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Topics: Biology
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  • 21
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    An ensemble strategy that significantly improves de novo assembly of microbial genomes from metagenomic next-generation sequencing data (2015)
    Oxford University Press
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    Publication Date: 2015-04-21
    Description: Next-generation sequencing (NGS) approaches rapidly produce millions to billions of short reads, which allow pathogen detection and discovery in human clinical, animal and environmental samples. A major limitation of sequence homology-based identification for highly divergent microorganisms is the short length of reads generated by most highly parallel sequencing technologies. Short reads require a high level of sequence similarities to annotated genes to confidently predict gene function or homology. Such recognition of highly divergent homologues can be improved by reference-free ( de novo ) assembly of short overlapping sequence reads into larger contigs. We describe an ensemble strategy that integrates the sequential use of various de Bruijn graph and overlap-layout-consensus assemblers with a novel partitioned sub-assembly approach. We also proposed new quality metrics that are suitable for evaluating metagenome de novo assembly. We demonstrate that this new ensemble strategy tested using in silico spike-in, clinical and environmental NGS datasets achieved significantly better contigs than current approaches.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 22
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    Distinguishing between productive and abortive promoters using a random forest classifier in Mycoplasma pneumoniae (2015)
    Oxford University Press
    Details
    Publication Date: 2015-04-21
    Description: Distinguishing between promoter-like sequences in bacteria that belong to true or abortive promoters, or to those that do not initiate transcription at all, is one of the important challenges in transcriptomics. To address this problem, we have studied the genome-reduced bacterium Mycoplasma pneumoniae , for which the RNAs associated with transcriptional start sites have been recently experimentally identified. We determined the contribution to transcription events of different genomic features: the –10, extended –10 and –35 boxes, the UP element, the bases surrounding the –10 box and the nearest-neighbor free energy of the promoter region. Using a random forest classifier and the aforementioned features transformed into scores, we could distinguish between true, abortive promoters and non-promoters with good –10 box sequences. The methods used in this characterization of promoters can be extended to other bacteria and have important applications for promoter design in bacterial genome engineering.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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    The economics of planting rights in wine production (2015)
    Oxford University Press
    Details
    Publication Date: 2015-05-26
    Description: The European Union (EU) is the world's largest wine producer, as well as the world's most regulated wine market. In 2007, the EU decided on a major reform of its wine policy. A crucial element was the abolishment of a system of planting rights to limit the planting of vineyards. However, after intense lobbying by opponents of the liberalisation, this decision was reversed in 2013. Despite the importance of planting rights in European (and hence global) wine production, and despite the fierce debates surrounding the reforms, no model exists to study the effects of this policy. We develop the first theoretical model of planting rights, integrating the markets for land, planting rights and wine to analyse efficiency and distributional effects. We use the model to study the effects of differences among EU member states in restrictions on trade in planting rights, the role of government reserves and the impact of imperfect enforcement.
    Keywords: Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0165-1587
    Electronic ISSN: 1464-3618
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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    The Yield of Plant Variety Protection (2015)
    Oxford University Press
    Details
    Publication Date: 2015-04-18
    Description: The prospects for plant variety protection to deliver improved varieties of self-pollinating crops is assessed using the experience of the Australian wheat breeding sector as a natural experiment. The analysis is based on detailed new data on the agronomic performance of all wheat varieties released by Australian breeders between 1976 and 2011. The results indicate that plant variety protection, and associated reforms, led to a substantial fall in breeder output. Qualitative evidence indicates that this was caused by a combination of fewer research spillovers, lower release standards, and a possible fall in total investment in breeding.
    Keywords: O34 - Intellectual Property Rights, Q16 - R&D ; Agricultural Technology ; Agricultural Extension Services, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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    Pathway analysis from lists of microRNAs: common pitfalls and alternative strategy (2015)
    Oxford University Press
    Details
    Publication Date: 2015-04-21
    Description: MicroRNAs (miRNAs) are involved in the regulation of gene expression at a post-transcriptional level. As such, monitoring miRNA expression has been increasingly used to assess their role in regulatory mechanisms of biological processes. In large scale studies, once miRNAs of interest have been identified, the target genes they regulate are often inferred using algorithms or databases. A pathway analysis is then often performed in order to generate hypotheses about the relevant biological functions controlled by the miRNA signature. Here we show that the method widely used in scientific literature to identify these pathways is biased and leads to inaccurate results. In addition to describing the bias and its origin we present an alternative strategy to identify potential biological functions specifically impacted by a miRNA signature. More generally, our study exemplifies the crucial need of relevant negative controls when developing, and using, bioinformatics methods.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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    Asymmetric Information and Profit Taking in Crop Insurance (2015)
    Oxford University Press
    Details
    Publication Date: 2015-02-11
    Description: Excess returns to producers insured by the Federal Crop Insurance Corporation can arise due to asymmetric information or from the design of the insurance programs themselves. Using unique, unit-level crop insurance contract data for major crops such as corn, soybeans, and wheat in five growing regions, we find evidence that producers in most regions may profit by selecting optional units, buy-up coverage, or by using transitional yields to participate in the federal crop insurance program. We also find evidence that advantages increase with land resource heterogeneity. However, the results do not support hypotheses that producers profit by selecting revenue insurance, nor that high levels of government "incompetence" exist in the design and administration of the crop insurance system.
    Keywords: Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 2040-5790
    Electronic ISSN: 2040-5804
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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    The Impact of the U.S. Sugar Program Redux (2015)
    Oxford University Press
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    Publication Date: 2015-02-11
    Description: We analyze the various welfare costs, transfers, trade, and employment consequences of the current U.S. sugar program for U.S. consumers, other sugar users, sugar refiners, cane and beet growing and processing industries, other associated agricultural sectors, and world markets. The removal of the sugar program would increase U.S. consumers' welfare by $2.9 to $3.5 billion each year and generate a modest job creation of 17,000 to 20,000 new jobs in food manufacturing and related industries. Imports of sugar containing products would fall dramatically, especially confectioneries substituting for domestic inputs under the sugar program. Sugar imports would rise substantially to 5–6 million short tons raw sugar equivalent. World sugar price increases would be minor, equivalent to about 1 cent per pound.
    Keywords: F13 - Trade Policy ; International Trade Organizations, Q17 - Agriculture in International Trade, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 2040-5790
    Electronic ISSN: 2040-5804
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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    A Triple-Hurdle Model of Production and Market Participation in Kenya's Dairy Market (2015)
    Oxford University Press
    Details
    Publication Date: 2015-07-10
    Description: Existing analyses of market participation are based on a "double-hurdle" modeling approach. Such models are appropriate only when all members of the population of interest actually produce the good. In some contexts, however (e.g., smallholder farmers), many members of the population do not produce particular goods that they could produce and that their neighbors do produce. Policies influencing market participation among producers may thus also induce additional farmers to become producers. Previous double-hurdle approaches do not allow explicitly for this possibility. To address these limitations, this article presents a "triple-hurdle" approach with an initial stage that includes nonproducers. The model is used to identify the factors associated with Kenyan smallholder farmers choosing to participate in dairy production, and the role that these producers choose to play (or not) in the marketplace. In the midst of debates underway over the privatization of the parastatal Kenya Creameries Company, new knowledge about smallholder participation in dairy could be an important contribution. Results suggest the importance of rural electrification, training, and improved grazing practices. We find that expected net sales are significantly higher when farmers have access to informal private markets. We also describe a version of the ordered tobit model that includes nonproducers and is nested in our triple-hurdle model. A likelihood ratio test shows the latter to be a significantly better fit to our data. We discuss how insights gained from this study differ from the insights that would come from a double-hurdle ordered tobit that also includes nonproducers.
    Keywords: C51 - Model Construction and Estimation, C81 - Methodology for Collecting, Estimating, and Organizing Microeconomic Data, O12 - Microeconomic Analyses of Economic Development, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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    The Political Economy of Food Price Volatility: The Case of Vietnam and Rice (2015)
    Oxford University Press
    Details
    Publication Date: 2015-07-10
    Description: This article argues that the structure of the Vietnamese rice export system is, in political economy terms, a rational response to the volatility present in the international rice market. In particular, it is argued that the Vietnamese Food Agency, along with VINAFOOD-1 and VINAFOOD-2, have been structured so that they can benefit from the domestic demands for export restrictions anticipated to occur as a consequence of international price volatility and the psychological demand of consumers for price stability. In turn, the actions of these agencies also contribute to international price volatility and the resulting demand for export restrictions. Since the political and economic elite in Vietnam obtain both political and economic power from this system, it is unlikely to be replaced with more effective and efficient policies to combat domestic price volatility. Thus, continued volatility in the price of rice can be expected.
    Keywords: N55 - Asia including Middle East, P26 - Political Economy ; Property Rights, Q17 - Agriculture in International Trade, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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    What Happens When Food Marketers Require Restrictive Farming Practices? (2015)
    Oxford University Press
    Details
    Publication Date: 2015-07-10
    Description: The dimensions that define a food product have expanded rapidly to include characteristics of the production process, marketing arrangements, and implications that production and consumption of the product have for the environment. Some market intermediaries have responded by requiring that their suppliers abide by restrictive production practices. We examine the economic effects of such restrictions and apply this analysis to limitations on the use of antibiotics in U.S. pork production. Results from conceptual and simulation analyses show that, in the absence of demand growth, less pork is sold due to higher costs in the restricted segment, and both pork consumers (on average) and producers are harmed. Demand growth of between 6–11% from adding new consumers who will consume the restricted (antibiotic-free) product but not the conventional product is needed to return consumer surplus to the level in the base case, and between 2–4% demand growth was required to return producer surplus to base. When restricted and conventional products are modeled using a vertical differentiation framework, results depend importantly on the ease with which consumers can switch to a seller who offers their desired product type. Significant distributional impacts among consumers are present when switching costs are prohibitive.
    Keywords: I18 - Government Policy ; Regulation ; Public Health, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0002-9092
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    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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    Asia-Pacific Integration with China versus the United States: Examining Trade Patterns under Heterogeneous Agricultural Sectors (2015)
    Oxford University Press
    Details
    Publication Date: 2015-09-12
    Description: This article examines bilateral trade patterns in the Asia-Pacific using a new model in which comparative advantage within the agricultural sector is linked to agro-ecological characteristics, and trade costs are product-specific. Bilateral market share is a function of productivity and trade costs. However, countries with similar land and climate characteristics systematically have high productivity in similar products making them disproportionately sensitive to changes in each other's trade costs. We use a random coefficients logit model to estimate a parametric distribution of comparative advantage and trade costs across products and calculate regional trade liberalization elasticities for each exporter in each import market. Unlike most existing models, the value of the elasticity depends on the degree to which liberalization includes competitors with similar comparative advantage within the agricultural sector. We find disproportionately larger trade elasticities under China-led liberalization relative to U.S.-led liberalization among close U.S. competitors compared to countries whose agricultural products are unlikely to compete head-to-head with U.S. exports. For the United States, we find that the "lost opportunity" cost of exclusion from regional liberalization is increasing in the extent to which its close competitors gain new access.
    Keywords: F13 - Trade Policy ; International Trade Organizations, F14 - Country and Industry Studies of Trade, F15 - Economic Integration, Q17 - Agriculture in International Trade, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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    Marketing Contracts and Crop Insurance (2015)
    Oxford University Press
    Details
    Publication Date: 2015-09-12
    Description: Contracts between farmers and intermediaries and crop insurers are important means for farmers to mitigate risks in modern U.S. agriculture. In this paper, we investigate the effect of crop insurance enrollment on contract terms and farmers’ participation in marketing contracts. Following Ligon (2003) , we set up a mechanism design framework to demonstrate an intermediary's contract design problem, where farmers are assumed to be utility maximizing agents. We depict farmers’ optimal choices of insurance coverage using the specification developed by Babcock (2012) . Our model shows that improved terms of crop insurance (lower premiums, higher subsidies) make contracts less appealing to farmers as mechanisms for mitigating risk. Therefore, intermediaries may revise their contract offers so that they are more attractive. However, improvements in contract terms are limited by their cost to the intermediaries and will not lead to expanded participation in contracts.
    Keywords: Q12 - Micro Analysis of Farm Firms, Farm Households, and Farm Input Markets, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0002-9092
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    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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    LARVA: an integrative framework for large-scale analysis of recurrent variants in noncoding annotations (2015)
    Oxford University Press
    Details
    Publication Date: 2015-09-30
    Description: In cancer research, background models for mutation rates have been extensively calibrated in coding regions, leading to the identification of many driver genes, recurrently mutated more than expected. Noncoding regions are also associated with disease; however, background models for them have not been investigated in as much detail. This is partially due to limited noncoding functional annotation. Also, great mutation heterogeneity and potential correlations between neighboring sites give rise to substantial overdispersion in mutation count, resulting in problematic background rate estimation. Here, we address these issues with a new computational framework called LARVA. It integrates variants with a comprehensive set of noncoding functional elements, modeling the mutation counts of the elements with a β-binomial distribution to handle overdispersion. LARVA, moreover, uses regional genomic features such as replication timing to better estimate local mutation rates and mutational hotspots. We demonstrate LARVA's effectiveness on 760 whole-genome tumor sequences, showing that it identifies well-known noncoding drivers, such as mutations in the TERT promoter. Furthermore, LARVA highlights several novel highly mutated regulatory sites that could potentially be noncoding drivers. We make LARVA available as a software tool and release our highly mutated annotations as an online resource ( larva.gersteinlab.org ).
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Topics: Biology
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    Producer heterogeneity and voting power in mandatory US agricultural marketing organisations (2015)
    Oxford University Press
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    Publication Date: 2015-10-31
    Description: We consider how cost heterogeneity and market power affect voting power in producer referenda for mandatory agricultural marketing organisations with generic promotion programmes in the United States. We measure voting power using the Banzhaf Power Index and propose a new version of this index based on the profit-maximising theory of the firm that provides an improved estimate of voting power. Examining several types of demand shifts and voting rules, we find that both Banzhaf Power and our new measure vary considerably depending on the market structure and level of cost heterogeneity.
    Keywords: D71 - Social Choice ; Clubs ; Committees ; Associations, D72 - Models of Political Processes: Rent-Seeking, Elections, Legislatures, and Voting Behavior, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0165-1587
    Electronic ISSN: 1464-3618
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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    The Risk Attitudes of U.S. Farmers (2015)
    Oxford University Press
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    Publication Date: 2015-11-06
    Description: I compare the distribution of risk attitudes of farm owners in the United States to nonfarm business owners and the general population using a measure of risk tolerance collected from national surveys. I find that farmers are significantly more tolerant of risk than the general population, though they are significantly less tolerant of risk than nonfarm business owners. Once demographic differences are controlled, farm and nonfarm business owners are more similar in their risk attitudes and both groups remain significantly more risk tolerant than the general population. First-generation farmers display greater risk tolerance than farmers who inherit operations from family members, as do farmers who have just begun operating a farm; neither pattern emerges among nonfarm business owners. The most risk tolerant farmers are young and male with larger operations, higher incomes, less formal education and close proximity to metropolitan centers. Among farmers, those with less diversified operations and those with specialty enterprises are more risk tolerant than other types of farmers. Crop farmers are less risk tolerant than fruit and vegetable farmers or farmers with specialty enterprises, while farmers who receive government payments or buy enterprise insurance are not significantly different in risk tolerance from farmers who eschew such opportunities. These findings stimulate questions about how farm programs and the distinct challenges of entry in the production agriculture sector shape the underlying distribution of key farmer characteristics such as risk tolerance.
    Keywords: D81 - Criteria for Decision-Making under Risk and Uncertainty, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 2040-5790
    Electronic ISSN: 2040-5804
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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    Discovery and characterization of Alu repeat sequences via precise local read assembly (2015)
    Oxford University Press
    Details
    Publication Date: 2015-12-02
    Description: Alu insertions have contributed to 〉11% of the human genome and ~30–35 Alu subfamilies remain actively mobile, yet the characterization of polymorphic Alu insertions from short-read data remains a challenge. We build on existing computational methods to combine Alu detection and de novo assembly of WGS data as a means to reconstruct the full sequence of insertion events from Illumina paired end reads. Comparison with published calls obtained using PacBio long-reads indicates a false discovery rate below 5%, at the cost of reduced sensitivity due to the colocation of reference and non-reference repeats. We generate a highly accurate call set of 1614 completely assembled Alu variants from 53 samples from the Human Genome Diversity Project (HGDP) panel. We utilize the reconstructed alternative insertion haplotypes to genotype 1010 fully assembled insertions, obtaining 〉99% agreement with genotypes obtained by PCR. In our assembled sequences, we find evidence of premature insertion mechanisms and observe 5' truncation in 16% of Alu Ya5 and Alu Yb8 insertions. The sites of truncation coincide with stem-loop structures and SRP9/14 binding sites in the Alu RNA, implicating L1 ORF2p pausing in the generation of 5' truncations. Additionally, we identified variable Alu J and Alu S elements that likely arose due to non-retrotransposition mechanisms.
    Keywords: Computational Methods, Genomics
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    Topics: Biology
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    The Effect of Food Deserts on the Body Mass Index of Elementary Schoolchildren (2015)
    Oxford University Press
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    Publication Date: 2015-12-13
    Description: Families in low-income neighborhoods sometimes lack access to supermarkets that provide a broad range of healthy foods. We investigate whether these so called "food deserts" play a role in childhood obesity using a statewide panel data set of Arkansas elementary schoolchildren. We use fixed-effects panel data regression models to estimate the average food desert effect. We next compare children who left (entered) food deserts to children who were always (never) in food deserts and homogenize samples for those whose food desert status changed as a result of a change in residence and those whose status changed only as a consequence of the entry or exit of a supermarket. We present evidence that exposure to food deserts is associated with higher z-scores for body mass index. On average, this is in the neighborhood of 0.04 standard deviations. The strongest evidence and largest association is among urban students and especially those that transition into food deserts from non-deserts. Our food desert estimates are similar in magnitude to findings reported in earlier work on diet and lifestyle interventions targeting similarly aged schoolchildren. That said, we are unable to conclude that the estimated food desert effect is causal because many of the transitions into or out of food deserts result from a change in residence, an event that is endogenous to the child's household. However, there is evidence that food deserts are a risk indicator and that food desert areas may be obesogenic in ways that other low-income neighborhoods are not.
    Keywords: I14 - Health and Inequality, I19 - Other, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0002-9092
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    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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    Examining the Relationship between the Use of Supermarkets and Over-nutrition in Indonesia (2015)
    Oxford University Press
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    Publication Date: 2015-03-14
    Description: This study examines the relationship between the use of modern food retailers and health outcomes using data from a survey of 1,180 urban households in Indonesia. The dependent variables include adult and child body-mass index and the share of individuals overweight and obese. After controlling for individual and household characteristics and using standard and Lewbel instrumental variable approaches to control for unobservable characteristics, we do not find a statistically significant relationship between use of supermarkets and adult nutrition measures. On the other hand, there is mixed evidence for a negative effect of supermarkets on child nutrition, particularly for those in high-income households.
    Keywords: I15 - Health and Economic Development, P46 - Consumer Economics ; Welfare and Poverty, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0002-9092
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    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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    Position Bias in Best-worst Scaling Surveys: A Case Study on Trust in Institutions (2015)
    Oxford University Press
    Details
    Publication Date: 2015-03-14
    Description: This paper investigates the effect of items’ physical position in the best-worst scaling technique. Although the best-worst scaling technique has been widely used in many fields, the literature has largely overlooked the phenomenon of consumers’ adoption of processing strategies while making their best-worst choices. We examine this issue in the context of consumers’ trust in institutions to provide information about a new food technology, nanotechnology, and its use in food processing. Our results show that approximately half of the consumers used position as a schematic cue when making choices. We find the position bias was particularly strong when consumers chose their most trustworthy institution compared to their least trustworthy institution. In light of our findings, we recommend that researchers in the field be aware of the possibility of position bias when designing best-worst scaling surveys. We also encourage researchers who have already collected best-worst data to investigate whether their data shows such heuristics.
    Keywords: C25 - Discrete Regression and Qualitative Choice Models, D12 - Consumer Economics: Empirical Analysis, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0002-9092
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    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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    Conditional mutual inclusive information enables accurate quantification of associations in gene regulatory networks (2015)
    Oxford University Press
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    Publication Date: 2015-03-14
    Description: Mutual information (MI), a quantity describing the nonlinear dependence between two random variables, has been widely used to construct gene regulatory networks (GRNs). Despite its good performance, MI cannot separate the direct regulations from indirect ones among genes. Although the conditional mutual information (CMI) is able to identify the direct regulations, it generally underestimates the regulation strength, i.e. it may result in false negatives when inferring gene regulations. In this work, to overcome the problems, we propose a novel concept, namely conditional mutual inclusive information (CMI2), to describe the regulations between genes. Furthermore, with CMI2, we develop a new approach, namely CMI2NI (CMI2-based network inference), for reverse-engineering GRNs. In CMI2NI, CMI2 is used to quantify the mutual information between two genes given a third one through calculating the Kullback–Leibler divergence between the postulated distributions of including and excluding the edge between the two genes. The benchmark results on the GRNs from DREAM challenge as well as the SOS DNA repair network in Escherichia coli demonstrate the superior performance of CMI2NI. Specifically, even for gene expression data with small sample size, CMI2NI can not only infer the correct topology of the regulation networks but also accurately quantify the regulation strength between genes. As a case study, CMI2NI was also used to reconstruct cancer-specific GRNs using gene expression data from The Cancer Genome Atlas (TCGA). CMI2NI is freely accessible at http://www.comp-sysbio.org/cmi2ni .
    Keywords: Computational Methods, Genomics
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    Topics: Biology
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    CODEX: a normalization and copy number variation detection method for whole exome sequencing (2015)
    Oxford University Press
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    Publication Date: 2015-04-02
    Description: High-throughput sequencing of DNA coding regions has become a common way of assaying genomic variation in the study of human diseases. Copy number variation (CNV) is an important type of genomic variation, but detecting and characterizing CNV from exome sequencing is challenging due to the high level of biases and artifacts. We propose CODEX, a normalization and CNV calling procedure for whole exome sequencing data. The Poisson latent factor model in CODEX includes terms that specifically remove biases due to GC content, exon capture and amplification efficiency, and latent systemic artifacts. CODEX also includes a Poisson likelihood-based recursive segmentation procedure that explicitly models the count-based exome sequencing data. CODEX is compared to existing methods on a population analysis of HapMap samples from the 1000 Genomes Project, and shown to be more accurate on three microarray-based validation data sets. We further evaluate performance on 222 neuroblastoma samples with matched normals and focus on a well-studied rare somatic CNV within the ATRX gene. We show that the cross-sample normalization procedure of CODEX removes more noise than normalizing the tumor against the matched normal and that the segmentation procedure performs well in detecting CNVs with nested structures.
    Keywords: Computational Methods, Genomics
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    Topics: Biology
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    Comprehensive discovery of DNA motifs in 349 human cells and tissues reveals new features of motifs (2015)
    Oxford University Press
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    Publication Date: 2015-01-10
    Description: Comprehensive motif discovery under experimental conditions is critical for the global understanding of gene regulation. To generate a nearly complete list of human DNA motifs under given conditions, we employed a novel approach to de novo discover significant co-occurring DNA motifs in 349 human DNase I hypersensitive site datasets. We predicted 845 to 1325 motifs in each dataset, for a total of 2684 non-redundant motifs. These 2684 motifs contained 54.02 to 75.95% of the known motifs in seven large collections including TRANSFAC. In each dataset, we also discovered 43 663 to 2 013 288 motif modules, groups of motifs with their binding sites co-occurring in a significant number of short DNA regions. Compared with known interacting transcription factors in eight resources, the predicted motif modules on average included 84.23% of known interacting motifs. We further showed new features of the predicted motifs, such as motifs enriched in proximal regions rarely overlapped with motifs enriched in distal regions, motifs enriched in 5' distal regions were often enriched in 3' distal regions, etc. Finally, we observed that the 2684 predicted motifs classified the cell or tissue types of the datasets with an accuracy of 81.29%. The resources generated in this study are available at http://server.cs.ucf.edu/predrem/ .
    Keywords: Computational Methods, Genomics
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    Topics: Biology
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    A framework for improving microRNA prediction in non-human genomes (2015)
    Oxford University Press
    Details
    Publication Date: 2015-11-17
    Description: The prediction of novel pre-microRNA (miRNA) from genomic sequence has received considerable attention recently. However, the majority of studies have focused on the human genome. Previous studies have demonstrated that sensitivity (correctly detecting true miRNA) is sustained when human-trained methods are applied to other species, however they have failed to report the dramatic drop in specificity (the ability to correctly reject non-miRNA sequences) in non-human genomes. Considering the ratio of true miRNA sequences to pseudo-miRNA sequences is on the order of 1:1000, such low specificity prevents the application of most existing tools to non-human genomes, as the number of false positives overwhelms the true predictions. We here introduce a framework (SMIRP) for creating species-specific miRNA prediction systems, leveraging sequence conservation and phylogenetic distance information. Substantial improvements in specificity and precision are obtained for four non-human test species when our framework is applied to three different prediction systems representing two types of classifiers (support vector machine and Random Forest), based on three different feature sets, with both human-specific and taxon-wide training data. The SMIRP framework is potentially applicable to all miRNA prediction systems and we expect substantial improvement in precision and specificity, while sustaining sensitivity, independent of the machine learning technique chosen.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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    Efficient exploration of pan-cancer networks by generalized covariance selection and interactive web content (2015)
    Oxford University Press
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    Publication Date: 2015-08-29
    Description: Statistical network modeling techniques are increasingly important tools to analyze cancer genomics data. However, current tools and resources are not designed to work across multiple diagnoses and technical platforms, thus limiting their applicability to comprehensive pan-cancer datasets such as The Cancer Genome Atlas (TCGA). To address this, we describe a new data driven modeling method, based on generalized Sparse Inverse Covariance Selection (SICS). The method integrates genetic, epigenetic and transcriptional data from multiple cancers, to define links that are present in multiple cancers, a subset of cancers, or a single cancer. It is shown to be statistically robust and effective at detecting direct pathway links in data from TCGA. To facilitate interpretation of the results, we introduce a publicly accessible tool ( cancerlandscapes.org ), in which the derived networks are explored as interactive web content, linked to several pathway and pharmacological databases. To evaluate the performance of the method, we constructed a model for eight TCGA cancers, using data from 3900 patients. The model rediscovered known mechanisms and contained interesting predictions. Possible applications include prediction of regulatory relationships, comparison of network modules across multiple forms of cancer and identification of drug targets.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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    A new approach for annotation of transposable elements using small RNA mapping (2015)
    Oxford University Press
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    Publication Date: 2015-07-25
    Description: Transposable elements (TEs) are mobile genomic DNA sequences found in most organisms. They so densely populate the genomes of many eukaryotic species that they are often the major constituents. With the rapid generation of many plant genome sequencing projects over the past few decades, there is an urgent need for improved TE annotation as a prerequisite for genome-wide studies. Analogous to the use of RNA-seq for gene annotation, we propose a new method for de novo TE annotation that uses as a guide 24 nt-siRNAs that are a part of TE silencing pathways. We use this new approach, called TASR (for Transposon Annotation using Small RNAs), for de novo annotation of TEs in Arabidopsis , rice and soybean and demonstrate that this strategy can be successfully applied for de novo TE annotation in plants. Executable PERL is available for download from: http://tasr-pipeline.sourceforge.net/
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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    The dynamics of dairy land use change with respect to the milk quota regime (2015)
    Oxford University Press
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    Publication Date: 2015-07-29
    Description: This article analyses the sequence of changes in land used for milk production on dairy farms before, during and towards the abolition of milk quotas. Using a unique dataset comprising farm level data of the Netherlands between 1971 and 2011 we estimate two duration models, analysing the time period between increases and decreases in dairy land use. The impact of milk quota, socio-economic, farm income and economic-political variables on the likelihood of a farm changing its land use are assessed. Results show that changes are highly farm specific, but that quota abolition will lead to a more dynamic dairy sector.
    Keywords: Q12 - Micro Analysis of Farm Firms, Farm Households, and Farm Input Markets, Q15 - Land Ownership and Tenure ; Land Reform ; Land Use ; Irrigation, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0165-1587
    Electronic ISSN: 1464-3618
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
    Published by Oxford University Press
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    Systematic integration of RNA-Seq statistical algorithms for accurate detection of differential gene expression patterns (2015)
    Oxford University Press
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    Publication Date: 2015-03-01
    Description: RNA-Seq is gradually becoming the standard tool for transcriptomic expression studies in biological research. Although considerable progress has been recorded in the development of statistical algorithms for the detection of differentially expressed genes using RNA-Seq data, the list of detected genes can differ significantly between algorithms. We present a new method (PANDORA) that combines multiple algorithms toward a summarized result, more efficiently reflecting true experimental outcomes. This is achieved through the systematic combination of several analysis algorithms, by weighting their outcomes according to their performance with realistically simulated data sets generated from real data. Results supported by the analysis of both simulated and real data from different organisms as well as correlation with PolII occupancy demonstrate that PANDORA improves the detection of differential expression. It accomplishes this by optimizing the tradeoff between standard performance measurements, such as precision and sensitivity.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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    Sparse expression bases in cancer reveal tumor drivers (2015)
    Oxford University Press
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    Publication Date: 2015-02-18
    Description: We define a new category of candidate tumor drivers in cancer genome evolution: ‘selected expression regulators’ (SERs)—genes driving dysregulated transcriptional programs in cancer evolution. The SERs are identified from genome-wide tumor expression data with a novel method, namely SPARROW ( SPAR se selected exp R essi O n regulators identified W ith penalized regression). SPARROW uncovers a previously unknown connection between cancer expression variation and driver events, by using a novel sparse regression technique. Our results indicate that SPARROW is a powerful complementary approach to identify candidate genes containing driver events that are hard to detect from sequence data, due to a large number of passenger mutations and lack of comprehensive sequence information from a sufficiently large number of samples. SERs identified by SPARROW reveal known driver mutations in multiple human cancers, along with known cancer-associated processes and survival-associated genes, better than popular methods for inferring gene expression networks. We demonstrate that when applied to acute myeloid leukemia expression data, SPARROW identifies an apoptotic biomarker ( PYCARD ) for an investigational drug obatoclax. The PYCARD and obatoclax association is validated in 30 AML patient samples.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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