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  • Computational Methods, Genomics  (140)
  • Food Policy  (110)
  • Oxford University Press  (250)
  • MDPI Publishing
  • 1
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    Socioeconomic and Demographic Determinants of the Nutritional Content of National School Lunch Program Entree Selections (2017)
    Oxford University Press
    Details
    Publication Date: 2017-01-05
    Description: New National School Lunch Program (NSLP) guidelines aim to reduce sodium and saturated fats, limit calories, and eliminate trans-fat and whole milk. This paper provides a novel approach to understanding how the healthfulness of NSLP participants’ entrée selections varies across socioeconomic and demographic groups. Unlike previous studies that rely on dietary recalls, we use a mixed logit model to examine students’ entrée choices in a school cafeteria. We estimate the likelihood that an entrée is selected from the available lunch choices as a function of the entrée’s nutrients (fat, carbohydrate, protein, and sodium) and entrée’s taste profile characteristics (e.g., Mexican, Pizza-like), as well as the student’s socio-economic and demographic characteristics. Using these estimates, we examine how changing the nutritional content of an offering impacts the probability of selecting each of the offerings. Free lunch recipients are more likely to choose entrées higher in fat but lower in sodium than other students. Full-price lunch recipients are the most responsive to changes in nutritional content of the offerings and are most likely to respond to changes in the nutritional content of the offered entrées by substituting a lunch brought from home for the school-purchased lunch. Replacing less healthy menu items with popular but healthier items reduces the selection of total calories, calories from fat, and sodium by approximately 4%, 18%, and 8%, respectively, over the study period. The new guidelines should be effective at improving the nutrition of school-age children, and potentially reducing childhood obesity, provided NSLP participation does not decline appreciably.
    Keywords: D12 - Consumer Economics: Empirical Analysis, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
    Published by Oxford University Press
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  • 2
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    Enabling the democratization of the genomics revolution with a fully integrated web-based bioinformatics platform (2017)
    Oxford University Press
    Details
    Publication Date: 2017-01-10
    Description: Continued advancements in sequencing technologies have fueled the development of new sequencing applications and promise to flood current databases with raw data. A number of factors prevent the seamless and easy use of these data, including the breadth of project goals, the wide array of tools that individually perform fractions of any given analysis, the large number of associated software/hardware dependencies, and the detailed expertise required to perform these analyses. To address these issues, we have developed an intuitive web-based environment with a wide assortment of integrated and cutting-edge bioinformatics tools in pre-configured workflows. These workflows, coupled with the ease of use of the environment, provide even novice next-generation sequencing users with the ability to perform many complex analyses with only a few mouse clicks and, within the context of the same environment, to visualize and further interrogate their results. This bioinformatics platform is an initial attempt at Empowering the Development of Genomics Expertise (EDGE) in a wide range of applications for microbial research.
    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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    Crop Choice, School Participation, and Child Labor in Developing Countries: Cotton Expansion in Burkina Faso (2017)
    Oxford University Press
    Details
    Publication Date: 2017-01-05
    Description: We estimate the effects of changes in cotton adoption on children’s schooling and child labor in rural Burkina Faso. Using time and spatial variations, we find evidence that expansion of cotton farming has led to an increase in enrollment and to a reduction of participation in child labor for girls. There are, however, no detectable effects on boys. In theory, cotton adoption could increase household income, leading to increased demand for schooling and reduced child labor. On the other hand, because children are productive on cotton farms, adoption of cotton could increase the opportunity cost of child time and the demand for child labor. We provide suggestive evidence showing that boys are more productive than girls on cotton farms. Taken together, the results suggest that the income effect from cotton adoption might have been larger than the wage effect for girls, hence the overall positive impacts on school enrollment for girls.
    Keywords: O12 - Microeconomic Analyses of Economic Development, O13 - Agriculture ; Natural Resources ; Energy ; Environment ; Other Primary Products, O15 - Human Resources ; Human Development ; Income Distribution ; Migration, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
    Published by Oxford University Press
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  • 4
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    Methods to increase reproducibility in differential gene expression via meta-analysis (2017)
    Oxford University Press
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    Publication Date: 2017-01-10
    Description: Findings from clinical and biological studies are often not reproducible when tested in independent cohorts. Due to the testing of a large number of hypotheses and relatively small sample sizes, results from whole-genome expression studies in particular are often not reproducible. Compared to single-study analysis, gene expression meta-analysis can improve reproducibility by integrating data from multiple studies. However, there are multiple choices in designing and carrying out a meta-analysis. Yet, clear guidelines on best practices are scarce. Here, we hypothesized that studying subsets of very large meta-analyses would allow for systematic identification of best practices to improve reproducibility. We therefore constructed three very large gene expression meta-analyses from clinical samples, and then examined meta-analyses of subsets of the datasets (all combinations of datasets with up to N/2 samples and K/2 datasets) compared to a ‘silver standard’ of differentially expressed genes found in the entire cohort. We tested three random-effects meta-analysis models using this procedure. We showed relatively greater reproducibility with more-stringent effect size thresholds with relaxed significance thresholds; relatively lower reproducibility when imposing extraneous constraints on residual heterogeneity; and an underestimation of actual false positive rate by Benjamini–Hochberg correction. In addition, multivariate regression showed that the accuracy of a meta-analysis increased significantly with more included datasets even when controlling for sample size.
    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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    A new molecular signature method for prediction of driver cancer pathways from transcriptional data (2016)
    Oxford University Press
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    Publication Date: 2016-06-21
    Description: Assigning cancer patients to the most effective treatments requires an understanding of the molecular basis of their disease. While DNA-based molecular profiling approaches have flourished over the past several years to transform our understanding of driver pathways across a broad range of tumors, a systematic characterization of key driver pathways based on RNA data has not been undertaken. Here we introduce a new approach for predicting the status of driver cancer pathways based on signature functions derived from RNA sequencing data. To identify the driver cancer pathways of interest, we mined DNA variant data from TCGA and nominated driver alterations in seven major cancer pathways in breast, ovarian and colon cancer tumors. The activation status of these driver pathways were then characterized using RNA sequencing data by constructing classification signature functions in training datasets and then testing the accuracy of the signatures in test datasets. The signature functions differentiate well tumors with nominated pathway activation from tumors with no signs of activation: average AUC equals to 0.83. Our results confirm that driver genomic alterations are distinctively displayed at the transcriptional level and that the transcriptional signatures can generally provide an alternative to DNA sequencing methods in detecting specific driver pathways.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 6
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    DanQ: a hybrid convolutional and recurrent deep neural network for quantifying the function of DNA sequences (2016)
    Oxford University Press
    Details
    Publication Date: 2016-06-21
    Description: Modeling the properties and functions of DNA sequences is an important, but challenging task in the broad field of genomics. This task is particularly difficult for non-coding DNA, the vast majority of which is still poorly understood in terms of function. A powerful predictive model for the function of non-coding DNA can have enormous benefit for both basic science and translational research because over 98% of the human genome is non-coding and 93% of disease-associated variants lie in these regions. To address this need, we propose DanQ, a novel hybrid convolutional and bi-directional long short-term memory recurrent neural network framework for predicting non-coding function de novo from sequence. In the DanQ model, the convolution layer captures regulatory motifs, while the recurrent layer captures long-term dependencies between the motifs in order to learn a regulatory ‘grammar’ to improve predictions. DanQ improves considerably upon other models across several metrics. For some regulatory markers, DanQ can achieve over a 50% relative improvement in the area under the precision-recall curve metric compared to related models. We have made the source code available at the github repository http://github.com/uci-cbcl/DanQ .
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 7
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    Phylogeny-aware identification and correction of taxonomically mislabeled sequences (2016)
    Oxford University Press
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    Publication Date: 2016-06-21
    Description: Molecular sequences in public databases are mostly annotated by the submitting authors without further validation. This procedure can generate erroneous taxonomic sequence labels. Mislabeled sequences are hard to identify, and they can induce downstream errors because new sequences are typically annotated using existing ones. Furthermore, taxonomic mislabelings in reference sequence databases can bias metagenetic studies which rely on the taxonomy. Despite significant efforts to improve the quality of taxonomic annotations, the curation rate is low because of the labor-intensive manual curation process. Here, we present SATIVA, a phylogeny-aware method to automatically identify taxonomically mislabeled sequences (‘mislabels’) using statistical models of evolution. We use the Evolutionary Placement Algorithm (EPA) to detect and score sequences whose taxonomic annotation is not supported by the underlying phylogenetic signal, and automatically propose a corrected taxonomic classification for those. Using simulated data, we show that our method attains high accuracy for identification (96.9% sensitivity/91.7% precision) as well as correction (94.9% sensitivity/89.9% precision) of mislabels. Furthermore, an analysis of four widely used microbial 16S reference databases (Greengenes, LTP, RDP and SILVA) indicates that they currently contain between 0.2% and 2.5% mislabels. Finally, we use SATIVA to perform an in-depth evaluation of alternative taxonomies for Cyanobacteria. SATIVA is freely available at https://github.com/amkozlov/sativa .
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 8
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    iGEMS: an integrated model for identification of alternative exon usage events (2016)
    Oxford University Press
    Details
    Publication Date: 2016-06-21
    Description: DNA microarrays and RNAseq are complementary methods for studying RNA molecules. Current computational methods to determine alternative exon usage (AEU) using such data require impractical visual inspection and still yield high false-positive rates. Integrated Gene and Exon Model of Splicing (iGEMS) adapts a gene-level residuals model with a gene size adjusted false discovery rate and exon-level analysis to circumvent these limitations. iGEMS was applied to two new DNA microarray datasets, including the high coverage Human Transcriptome Arrays 2.0 and performance was validated using RT-qPCR. First, AEU was studied in adipocytes treated with ( n = 9) or without ( n = 8) the anti-diabetes drug, rosiglitazone. iGEMS identified 555 genes with AEU, and robust verification by RT-qPCR (~90%). Second, in a three-way human tissue comparison (muscle, adipose and blood, n = 41) iGEMS identified 4421 genes with at least one AEU event, with excellent RT-qPCR verification (95%, n = 22). Importantly, iGEMS identified a variety of AEU events, including 3'UTR extension, as well as exon inclusion/exclusion impacting on protein kinase and extracellular matrix domains. In conclusion, iGEMS is a robust method for identification of AEU while the variety of exon usage between human tissues is 5–10 times more prevalent than reported by the Genotype-Tissue Expression consortium using RNA sequencing.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 9
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    TCGAbiolinks: an R/Bioconductor package for integrative analysis of TCGA data (2016)
    Oxford University Press
    Details
    Publication Date: 2016-05-06
    Description: The Cancer Genome Atlas (TCGA) research network has made public a large collection of clinical and molecular phenotypes of more than 10 000 tumor patients across 33 different tumor types. Using this cohort, TCGA has published over 20 marker papers detailing the genomic and epigenomic alterations associated with these tumor types. Although many important discoveries have been made by TCGA's research network, opportunities still exist to implement novel methods, thereby elucidating new biological pathways and diagnostic markers. However, mining the TCGA data presents several bioinformatics challenges, such as data retrieval and integration with clinical data and other molecular data types (e.g. RNA and DNA methylation). We developed an R/Bioconductor package called TCGAbiolinks to address these challenges and offer bioinformatics solutions by using a guided workflow to allow users to query, download and perform integrative analyses of TCGA data. We combined methods from computer science and statistics into the pipeline and incorporated methodologies developed in previous TCGA marker studies and in our own group. Using four different TCGA tumor types (Kidney, Brain, Breast and Colon) as examples, we provide case studies to illustrate examples of reproducibility, integrative analysis and utilization of different Bioconductor packages to advance and accelerate novel discoveries.
    Keywords: Computational Methods, Genomics
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    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 10
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    Robust detection of alternative splicing in a population of single cells (2016)
    Oxford University Press
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    Publication Date: 2016-05-06
    Description: Single cell RNA-seq experiments provide valuable insight into cellular heterogeneity but suffer from low coverage, 3' bias and technical noise. These unique properties of single cell RNA-seq data make study of alternative splicing difficult, and thus most single cell studies have restricted analysis of transcriptome variation to the gene level. To address these limitations, we developed SingleSplice, which uses a statistical model to detect genes whose isoform usage shows biological variation significantly exceeding technical noise in a population of single cells. Importantly, SingleSplice is tailored to the unique demands of single cell analysis, detecting isoform usage differences without attempting to infer expression levels for full-length transcripts. Using data from spike-in transcripts, we found that our approach detects variation in isoform usage among single cells with high sensitivity and specificity. We also applied SingleSplice to data from mouse embryonic stem cells and discovered a set of genes that show significant biological variation in isoform usage across the set of cells. A subset of these isoform differences are linked to cell cycle stage, suggesting a novel connection between alternative splicing and the cell cycle.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 11
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    CARGO: effective format-free compressed storage of genomic information (2016)
    Oxford University Press
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    Publication Date: 2016-07-09
    Description: The recent super-exponential growth in the amount of sequencing data generated worldwide has put techniques for compressed storage into the focus. Most available solutions, however, are strictly tied to specific bioinformatics formats, sometimes inheriting from them suboptimal design choices; this hinders flexible and effective data sharing. Here, we present CARGO (Compressed ARchiving for GenOmics), a high-level framework to automatically generate software systems optimized for the compressed storage of arbitrary types of large genomic data collections. Straightforward applications of our approach to FASTQ and SAM archives require a few lines of code, produce solutions that match and sometimes outperform specialized format-tailored compressors and scale well to multi-TB datasets. All CARGO software components can be freely downloaded for academic and non-commercial use from http://bio-cargo.sourceforge.net .
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 12
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    InPhaDel: integrative shotgun and proximity-ligation sequencing to phase deletions with single nucleotide polymorphisms (2016)
    Oxford University Press
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    Publication Date: 2016-07-09
    Description: Phasing of single nucleotide (SNV), and structural variations into chromosome-wide haplotypes in humans has been challenging, and required either trio sequencing or restricting phasing to population-based haplotypes. Selvaraj et al . demonstrated single individual SNV phasing is possible with proximity ligated (HiC) sequencing. Here, we demonstrate HiC can phase structural variants into phased scaffolds of SNVs. Since HiC data is noisy, and SV calling is challenging, we applied a range of supervised classification techniques, including Support Vector Machines and Random Forest, to phase deletions. Our approach was demonstrated on deletion calls and phasings on the NA12878 human genome. We used three NA12878 chromosomes and simulated chromosomes to train model parameters. The remaining NA12878 chromosomes withheld from training were used to evaluate phasing accuracy. Random Forest had the highest accuracy and correctly phased 86% of the deletions with allele-specific read evidence. Allele-specific read evidence was found for 76% of the deletions. HiC provides significant read evidence for accurately phasing 33% of the deletions. Also, eight of eight top ranked deletions phased by only HiC were validated using long range polymerase chain reaction and Sanger. Thus, deletions from a single individual can be accurately phased using a combination of shotgun and proximity ligation sequencing. InPhaDel software is available at: http://l337x911.github.io/inphadel/.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 13
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    Redundans: an assembly pipeline for highly heterozygous genomes (2016)
    Oxford University Press
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    Publication Date: 2016-07-09
    Description: Many genomes display high levels of heterozygosity (i.e. presence of different alleles at the same loci in homologous chromosomes), being those of hybrid organisms an extreme such case. The assembly of highly heterozygous genomes from short sequencing reads is a challenging task because it is difficult to accurately recover the different haplotypes. When confronted with highly heterozygous genomes, the standard assembly process tends to collapse homozygous regions and reports heterozygous regions in alternative contigs. The boundaries between homozygous and heterozygous regions result in multiple assembly paths that are hard to resolve, which leads to highly fragmented assemblies with a total size larger than expected. This, in turn, causes numerous problems in downstream analyses such as fragmented gene models, wrong gene copy number, or broken synteny. To circumvent these caveats we have developed a pipeline that specifically deals with the assembly of heterozygous genomes by introducing a step to recognise and selectively remove alternative heterozygous contigs. We tested our pipeline on simulated and naturally-occurring heterozygous genomes and compared its accuracy to other existing tools. Our method is freely available at https://github.com/Gabaldonlab/redundans .
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 14
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    Estimating the Relationship between Food Prices and Food Consumption--Methods Matter (2016)
    Oxford University Press
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    Publication Date: 2016-08-20
    Description: Concerns about the growing prevalence of obesity worldwide have led researchers and policy makers to investigate the potential health impact of fiscal policies such as taxes on unhealthy foods. A common instrument used to measure the relationship between food prices and food consumption is the price elasticity of demand. Using meta-regression analysis we assessed how differences in methodological approaches to estimating demand affected food price elasticities. Most methodological differences had a statistically significant impact on elasticity estimates, which stresses the importance of using meta-estimates or testing the sensitivity of simulation outcomes to a range of elasticity parameters before drawing policy conclusions.
    Keywords: D11 - Consumer Economics: Theory, H31 - Household, 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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  • 15
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    Mixed Integer Linear Programming based machine learning approach identifies regulators of telomerase in yeast (2016)
    Oxford University Press
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    Publication Date: 2016-06-03
    Description: Understanding telomere length maintenance mechanisms is central in cancer biology as their dysregulation is one of the hallmarks for immortalization of cancer cells. Important for this well-balanced control is the transcriptional regulation of the telomerase genes. We integrated Mixed Integer Linear Programming models into a comparative machine learning based approach to identify regulatory interactions that best explain the discrepancy of telomerase transcript levels in yeast mutants with deleted regulators showing aberrant telomere length, when compared to mutants with normal telomere length. We uncover novel regulators of telomerase expression, several of which affect histone levels or modifications. In particular, our results point to the transcription factors Sum1, Hst1 and Srb2 as being important for the regulation of EST1 transcription, and we validated the effect of Sum1 experimentally. We compiled our machine learning method leading to a user friendly package for R which can straightforwardly be applied to similar problems integrating gene regulator binding information and expression profiles of samples of e.g. different phenotypes, diseases or treatments.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 16
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    f-divergence cutoff index to simultaneously identify differential expression in the integrated transcriptome and proteome (2016)
    Oxford University Press
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    Publication Date: 2016-06-03
    Description: The ability to integrate ‘omics’ (i.e. transcriptomics and proteomics) is becoming increasingly important to the understanding of regulatory mechanisms. There are currently no tools available to identify differentially expressed genes (DEGs) across different ‘omics’ data types or multi-dimensional data including time courses. We present fCI (f-divergence Cut-out Index), a model capable of simultaneously identifying DEGs from continuous and discrete transcriptomic, proteomic and integrated proteogenomic data. We show that fCI can be used across multiple diverse sets of data and can unambiguously find genes that show functional modulation, developmental changes or misregulation. Applying fCI to several proteogenomics datasets, we identified a number of important genes that showed distinctive regulation patterns. The package fCI is available at R Bioconductor and http://software.steenlab.org/fCI/ .
    Keywords: Computational Methods, Genomics
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    Topics: Biology
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  • 17
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    CLASS2: accurate and efficient splice variant annotation from RNA-seq reads (2016)
    Oxford University Press
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    Publication Date: 2016-06-03
    Description: Next generation sequencing of cellular RNA is making it possible to characterize genes and alternative splicing in unprecedented detail. However, designing bioinformatics tools to accurately capture splicing variation has proven difficult. Current programs can find major isoforms of a gene but miss lower abundance variants, or are sensitive but imprecise. CLASS2 is a novel open source tool for accurate genome-guided transcriptome assembly from RNA-seq reads based on the model of splice graph. An extension of our program CLASS, CLASS2 jointly optimizes read patterns and the number of supporting reads to score and prioritize transcripts, implemented in a novel, scalable and efficient dynamic programming algorithm. When compared against reference programs, CLASS2 had the best overall accuracy and could detect up to twice as many splicing events with precision similar to the best reference program. Notably, it was the only tool to produce consistently reliable transcript models for a wide range of applications and sequencing strategies, including ribosomal RNA-depleted samples. Lightweight and multi-threaded, CLASS2 requires 〈3GB RAM and can analyze a 350 million read set within hours, and can be widely applied to transcriptomics studies ranging from clinical RNA sequencing, to alternative splicing analyses, and to the annotation of new genomes.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Topics: Biology
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  • 18
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    FACETS: allele-specific copy number and clonal heterogeneity analysis tool for high-throughput DNA sequencing (2016)
    Oxford University Press
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    Publication Date: 2016-09-20
    Description: Allele-specific copy number analysis (ASCN) from next generation sequencing (NGS) data can greatly extend the utility of NGS beyond the identification of mutations to precisely annotate the genome for the detection of homozygous/heterozygous deletions, copy-neutral loss-of-heterozygosity (LOH), allele-specific gains/amplifications. In addition, as targeted gene panels are increasingly used in clinical sequencing studies for the detection of ‘actionable’ mutations and copy number alterations to guide treatment decisions, accurate, tumor purity-, ploidy- and clonal heterogeneity-adjusted integer copy number calls are greatly needed to more reliably interpret NGS-based cancer gene copy number data in the context of clinical sequencing. We developed FACETS, an ASCN tool and open-source software with a broad application to whole genome, whole-exome, as well as targeted panel sequencing platforms. It is a fully integrated stand-alone pipeline that includes sequencing BAM file post-processing, joint segmentation of total- and allele-specific read counts, and integer copy number calls corrected for tumor purity, ploidy and clonal heterogeneity, with comprehensive output and integrated visualization. We demonstrate the application of FACETS using The Cancer Genome Atlas (TCGA) whole-exome sequencing of lung adenocarcinoma samples. We also demonstrate its application to a clinical sequencing platform based on a targeted gene panel.
    Keywords: Computational Methods, Genomics
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  • 19
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    A genome-wide approach for detecting novel insertion-deletion variants of mid-range size (2016)
    Oxford University Press
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    Publication Date: 2016-09-03
    Description: We present SWAN, a statistical framework for robust detection of genomic structural variants in next-generation sequencing data and an analysis of mid-range size insertion and deletions (〈10 Kb) for whole genome analysis and DNA mixtures. To identify these mid-range size events, SWAN collectively uses information from read-pair, read-depth and one end mapped reads through statistical likelihoods based on Poisson field models. SWAN also uses soft-clip/split read remapping to supplement the likelihood analysis and determine variant boundaries. The accuracy of SWAN is demonstrated by in silico spike-ins and by identification of known variants in the NA12878 genome. We used SWAN to identify a series of novel set of mid-range insertion/deletion detection that were confirmed by targeted deep re-sequencing. An R package implementation of SWAN is open source and freely available.
    Keywords: Computational Methods, Genomics
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    Topics: Biology
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  • 20
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    Cuba's Agricultural Transition and Food Security in a Global Perspective (2016)
    Oxford University Press
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    Publication Date: 2016-08-20
    Description: This paper reviews the situation in the agricultural sector and food security in Cuba, and particularly the transformations that have (not) taken place since 1990. We compare the Cuban transition with transitions in other "transition countries" and show that Cuba does not easily fit into one of the transition patterns, and, in a way, has characteristics of "a bit of everything". To conclude, we discuss the (potential) effects of the recent policy changes and the new economic reforms that were announced.
    Keywords: O13 - Agriculture ; Natural Resources ; Energy ; Environment ; Other Primary Products, P21 - Planning, Coordination, and Reform, 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
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  • 21
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    Comprehensive analysis of high-throughput screens with HiTSeekR (2016)
    Oxford University Press
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    Publication Date: 2016-08-20
    Description: High-throughput screening (HTS) is an indispensable tool for drug (target) discovery that currently lacks user-friendly software tools for the robust identification of putative hits from HTS experiments and for the interpretation of these findings in the context of systems biology. We developed HiTSeekR as a one-stop solution for chemical compound screens, siRNA knock-down and CRISPR/Cas9 knock-out screens, as well as microRNA inhibitor and -mimics screens. We chose three use cases that demonstrate the potential of HiTSeekR to fully exploit HTS screening data in quite heterogeneous contexts to generate novel hypotheses for follow-up experiments: (i) a genome-wide RNAi screen to uncover modulators of TNFα, (ii) a combined siRNA and miRNA mimics screen on vorinostat resistance and (iii) a small compound screen on KRAS synthetic lethality. HiTSeekR is publicly available at http://hitseekr.compbio.sdu.dk . It is the first approach to close the gap between raw data processing, network enrichment and wet lab target generation for various HTS screen types.
    Keywords: Computational Methods, Genomics
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  • 22
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    Who Really Benefits from Agricultural Subsidies? Evidence from Field-level Data (2016)
    Oxford University Press
    Details
    Publication Date: 2016-07-09
    Description: If agricultural subsidies are largely capitalized into farmland values through their effect on rental rates, then expanding support for agriculture may not benefit farmers who rent the land they farm. Existing evidence on the incidence of subsidies on cash rental rates is mixed. Identification is obscured by unobserved or imprecisely measured factors that tend to be correlated with subsidies, especially land quality and time-varying factors like commodity prices and adverse weather events. A problem that has received less attention is the fact that subsidies and land quality on rented land may differ from owned land. Since most farms possess both rented and owned acreage, farm-level measures of subsidies, land values, and rental rates may bias estimated incidence. Using a new, field-level data set that, for the first time, precisely links subsidies to land parcels, we show that this bias is considerable: where farm-level estimates suggest an incidence of 42–49 cents of the marginal subsidy dollar, field-level estimates from the same farms indicate that landlords capture just 20–28 cents. The size of the farm and the duration of the rental arrangement have substantial effects. Incidence falls by 5–15 cents when doubling total operated acres, and the incidence falls by 0.1–0.8 cents with each additional year of the rental arrangement. Low incidence of subsidies on rents combined with the farm-size and duration effects suggest that farmers renting land have monopsony power.
    Keywords: H22 - Incidence, Q14 - Agricultural Finance, Q15 - Land Ownership and Tenure ; Land Reform ; Land Use ; Irrigation, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
    Published by Oxford University Press
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    Trade Policy Coordination and Food Price Volatility (2016)
    Oxford University Press
    Details
    Publication Date: 2016-07-09
    Description: Many countries adjust their trade policies counter-cyclically with food prices, to the extent that the use of restrictions by food-exporting countries has occasionally threatened the food security of food-importing countries. These trade policies are inconsistent with the terms-of-trade motivation often retained to characterize the payoff frontier of self-enforcing trade agreements, as they can worsen the terms of trade of the countries that apply them. This article analyzes trade policy coordination when trade policies are driven by terms-of-trade effects and a desire to reduce domestic food price volatility. This framework implies that importing and exporting countries have incentives to deviate from cooperation at different periods: the latter when prices are high and the former when prices are low. Since staple food prices tend to have asymmetric distributions, with more prices below than above the mean but with occasional spikes, a self-enforcing agreement generates asymmetric outcomes. Without cooperation, an importing country uses its trade policy more frequently because of the concentration of prices below the mean, but an exporting country has a greater incentive to deviate from a cooperative trade policy because positive deviations from the mean price are larger than negative ones. Thus, the asymmetry of the distribution of commodity prices can make it more difficult to discipline export taxes than tariffs in trade agreements.
    Keywords: F13 - Trade Policy ; International Trade Organizations, 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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    Interactions between CAP Agricultural and Agri-Environmental Subsidies and Their Effects on the Uptake of Organic Farming (2016)
    Oxford University Press
    Details
    Publication Date: 2016-07-09
    Description: We analyze the effects of the interactions that the two pillars of the European Union Common Agricultural Policy—market support and rural development—have on farmers’ uptake of organic farming practices. Special attention is given to the 2003 reform, which substantially altered the relative importance of the two types of support by decoupling direct agricultural payments from the production of a specific crop. In our empirical analysis we study the case of Sweden, making use of the variation in the timing of farmers’ decisions regarding participation in support programs. We estimate a dynamic non-linear unobserved effects probit model to account for unobserved individual heterogeneity and state dependence. Our results indicate the existence of a negative effect of the market support system in place when organic farming techniques were adopted before the 2003 reform. However, this effect is reversed by the introduction of decoupling. Furthermore, the effects of support differ between certified and non-certified organic production: both pillars have significant effects on non-certified organic farming, whereas certified organic farming is exclusively driven by agro-environmental subsidies.
    Keywords: C23 - Models with Panel Data, Q12 - Micro Analysis of Farm Firms, Farm Households, and Farm Input Markets, 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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    Beegle: from literature mining to disease-gene discovery (2016)
    Oxford University Press
    Details
    Publication Date: 2016-01-30
    Description: Disease-gene identification is a challenging process that has multiple applications within functional genomics and personalized medicine. Typically, this process involves both finding genes known to be associated with the disease (through literature search) and carrying out preliminary experiments or screens (e.g. linkage or association studies, copy number analyses, expression profiling) to determine a set of promising candidates for experimental validation. This requires extensive time and monetary resources. We describe Beegle , an online search and discovery engine that attempts to simplify this process by automating the typical approaches. It starts by mining the literature to quickly extract a set of genes known to be linked with a given query, then it integrates the learning methodology of Endeavour (a gene prioritization tool) to train a genomic model and rank a set of candidate genes to generate novel hypotheses. In a realistic evaluation setup, Beegle has an average recall of 84% in the top 100 returned genes as a search engine, which improves the discovery engine by 12.6% in the top 5% prioritized genes. Beegle is publicly available at http://beegle.esat.kuleuven.be/ .
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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    A computational method for studying the relation between alternative splicing and DNA methylation (2016)
    Oxford University Press
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    Publication Date: 2016-01-30
    Description: Alternative splicing is an important mechanism in eukaryotes that expands the transcriptome and proteome significantly. It plays an important role in a number of biological processes. Understanding its regulation is hence an important challenge. Recently, increasing evidence has been collected that supports an involvement of intragenic DNA methylation in the regulation of alternative splicing. The exact mechanisms of regulation, however, are largely unknown, and speculated to be complex: different methylation profiles might exist, each of which could be associated with a different regulation mechanism. We present a computational technique that is able to determine such stable methylation patterns and allows to correlate these patterns with inclusion propensity of exons. Pattern detection is based on dynamic time warping (DTW) of methylation profiles, a sophisticated similarity measure for signals that can be non-trivially transformed. We design a flexible self-organizing map approach to pattern grouping. Exemplary application on available data sets indicates that stable patterns which correlate non-trivially with exon inclusion do indeed exist. To improve the reliability of these predictions, further studies on larger data sets will be required. We have thus taken great care that our software runs efficiently on modern hardware, so that it can support future studies on large-scale data sets.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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    BubbleTree: an intuitive visualization to elucidate tumoral aneuploidy and clonality using next generation sequencing data (2016)
    Oxford University Press
    Details
    Publication Date: 2016-03-01
    Description: Tumors are characterized by properties of genetic instability, heterogeneity, and significant oligoclonality. Elucidating this intratumoral heterogeneity is challenging but important. In this study, we propose a framework, BubbleTree, to characterize the tumor clonality using next generation sequencing (NGS) data. BubbleTree simultaneously elucidates the complexity of a tumor biopsy, estimating cancerous cell purity, tumor ploidy, allele-specific copy number, and clonality and represents this in an intuitive graph. We further developed a three-step heuristic method to automate the interpretation of the BubbleTree graph, using a divide-and-conquer strategy. In this study, we demonstrated the performance of BubbleTree with comparisons to similar commonly used tools such as THetA2, ABSOLUTE, AbsCN-seq and ASCAT, using both simulated and patient-derived data. BubbleTree outperformed these tools, particularly in identifying tumor subclonal populations and polyploidy. We further demonstrated BubbleTree's utility in tracking clonality changes from patients’ primary to metastatic tumor and dating somatic single nucleotide and copy number variants along the tumor clonal evolution. Overall, the BubbleTree graph and corresponding model is a powerful approach to provide a comprehensive spectrum of the heterogeneous tumor karyotype in human tumors. BubbleTree is R-based and freely available to the research community ( https://www.bioconductor.org/packages/release/bioc/html/BubbleTree.html ).
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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    Quantification of read species behavior within whole genome sequencing of cancer genomes for the stratification and visualization of genomic variation (2016)
    Oxford University Press
    Details
    Publication Date: 2016-05-20
    Description: The cancer genome is abnormal genome, and the ability to monitor its sequence had undergone a technological revolution. Yet prognosis and diagnosis remain an expert-based decision, with only limited abilities to provide machine-based decisions. We introduce a heterogeneity-based method for stratifying and visualizing whole-genome sequencing (WGS) reads. This method uses the heterogeneity within WGS reads to markedly reduce the dimensionality of next-generation sequencing data; it is available through the tool HiBS (Heterogeneity-Based Subclassification) that allows cancer sample classification. We validated HiBS using 〉200 WGS samples from nine different cancer types from The Cancer Genome Atlas (TCGA). With HiBS, we show progress with two WGS related issues: (i) differentiation between normal (NB) and tumor (TP) samples based solely on the information structure of their WGS data, and (ii) identification of specific regions of chromosomal amplification/deletion and their association with tumor stage. By comparing results to those obtained through available WGS analyses tools, we demonstrate some of the novelties obtained by the approach implemented in HiBS and also show nearly perfect normal/tumor classification, used to identify known and unknown chromosomal aberrations. Finally, the HiBS index has been associated with breast cancer tumor stage.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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    Circular RNA profile in gliomas revealed by identification tool UROBORUS (2016)
    Oxford University Press
    Details
    Publication Date: 2016-05-20
    Description: Recent evidence suggests that many endogenous circular RNAs (circRNAs) may play roles in biological processes. However, the expression patterns and functions of circRNAs in human diseases are not well understood. Computationally identifying circRNAs from total RNA-seq data is a primary step in studying their expression pattern and biological roles. In this work, we have developed a computational pipeline named UROBORUS to detect circRNAs in total RNA-seq data. By applying UROBORUS to RNA-seq data from 46 gliomas and normal brain samples, we detected thousands of circRNAs supported by at least two read counts, followed by successful experimental validation on 24 circRNAs from the randomly selected 27 circRNAs. UROBORUS is an efficient tool that can detect circRNAs with low expression levels in total RNA-seq without RNase R treatment. The circRNAs expression profiling revealed more than 476 circular RNAs differentially expressed in control brain tissues and gliomas. Together with parental gene expression, we found that circRNA and its parental gene have diversified expression patterns in gliomas and control brain tissues. This study establishes an efficient and sensitive approach for predicting circRNAs using total RNA-seq data. The UROBORUS pipeline can be accessed freely for non-commercial purposes at http://uroborus.openbioinformatics.org/ .
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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    Modeling the combined effect of RNA-binding proteins and microRNAs in post-transcriptional regulation (2016)
    Oxford University Press
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    Publication Date: 2016-05-20
    Description: Recent studies show that RNA-binding proteins (RBPs) and microRNAs (miRNAs) function in coordination with each other to control post-transcriptional regulation (PTR). Despite this, the majority of research to date has focused on the regulatory effect of individual RBPs or miRNAs. Here, we mapped both RBP and miRNA binding sites on human 3'UTRs and utilized this collection to better understand PTR. We show that the transcripts that lack competition for HuR binding are destabilized more after HuR depletion. We also confirm this finding for PUM1(2) by measuring genome-wide expression changes following the knockdown of PUM1(2) in HEK293 cells. Next, to find potential cooperative interactions, we identified the pairs of factors whose sites co-localize more often than expected by random chance. Upon examining these results for PUM1(2), we found that transcripts where the sites of PUM1(2) and its interacting miRNA form a stem-loop are more stabilized upon PUM1(2) depletion. Finally, using dinucleotide frequency and counts of regulatory sites as features in a regression model, we achieved an AU-ROC of 0.86 in predicting mRNA half-life in BEAS-2B cells. Altogether, our results suggest that future studies of PTR must consider the combined effects of RBPs and miRNAs, as well as their interactions.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Using intron position conservation for homology-based gene prediction (2016)
    Oxford University Press
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    Publication Date: 2016-05-20
    Description: Annotation of protein-coding genes is very important in bioinformatics and biology and has a decisive influence on many downstream analyses. Homology-based gene prediction programs allow for transferring knowledge about protein-coding genes from an annotated organism to an organism of interest. Here, we present a homology-based gene prediction program called GeMoMa. GeMoMa utilizes the conservation of intron positions within genes to predict related genes in other organisms. We assess the performance of GeMoMa and compare it with state-of-the-art competitors on plant and animal genomes using an extended best reciprocal hit approach. We find that GeMoMa often makes more precise predictions than its competitors yielding a substantially increased number of correct transcripts. Subsequently, we exemplarily validate GeMoMa predictions using Sanger sequencing. Finally, we use RNA-seq data to compare the predictions of homology-based gene prediction programs, and find again that GeMoMa performs well. Hence, we conclude that exploiting intron position conservation improves homology-based gene prediction, and we make GeMoMa freely available as command-line tool and Galaxy integration.
    Keywords: Computational Methods, Genomics
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    Electronic ISSN: 1362-4962
    Topics: Biology
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    Comparison of circular RNA prediction tools (2016)
    Oxford University Press
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    Publication Date: 2016-04-08
    Description: CircRNAs are novel members of the non-coding RNA family. For several decades circRNAs have been known to exist, however only recently the widespread abundance has become appreciated. Annotation of circRNAs depends on sequencing reads spanning the backsplice junction and therefore map as non-linear reads in the genome. Several pipelines have been developed to specifically identify these non-linear reads and consequently predict the landscape of circRNAs based on deep sequencing datasets. Here, we use common RNAseq datasets to scrutinize and compare the output from five different algorithms; circRNA_finder, find_circ, CIRCexplorer, CIRI, and MapSplice and evaluate the levels of bona fide and false positive circRNAs based on RNase R resistance. By this approach, we observe surprisingly dramatic differences between the algorithms specifically regarding the highly expressed circRNAs and the circRNAs derived from proximal splice sites. Collectively, this study emphasizes that circRNA annotation should be handled with care and that several algorithms should ideally be combined to achieve reliable predictions.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Price Differences across Farmers Markets, Roadside Stands, and Supermarkets in North Carolina (2016)
    Oxford University Press
    Details
    Publication Date: 2016-05-19
    Description: Whether direct farmer-to-consumer outlets compete with supermarkets on produce prices remains an empirical question; marketing costs are not consistently higher in one retail channel or the other. This study compared prices of 29 fruits and vegetables across North Carolina farmers’ markets, roadside stands, and supermarkets. Larger farmers’ markets had higher prices: three fruits and one vegetable were cheaper at a direct outlet, while four vegetables were cheaper at supermarkets. Weighting item prices by consumption share attenuated differences in mean price across outlets. Direct-retail outlets are price competitive and should be considered among other tools to boost fresh fruit and vegetable intake.
    Keywords: 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
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    Comprehensive evaluation of fusion transcript detection algorithms and a meta-caller to combine top performing methods in paired-end RNA-seq data (2016)
    Oxford University Press
    Details
    Publication Date: 2016-03-19
    Description: Background: Fusion transcripts are formed by either fusion genes (DNA level) or trans-splicing events (RNA level). They have been recognized as a promising tool for diagnosing, subtyping and treating cancers. RNA-seq has become a precise and efficient standard for genome-wide screening of such aberration events. Many fusion transcript detection algorithms have been developed for paired-end RNA-seq data but their performance has not been comprehensively evaluated to guide practitioners. In this paper, we evaluated 15 popular algorithms by their precision and recall trade-off, accuracy of supporting reads and computational cost. We further combine top-performing methods for improved ensemble detection. Results: Fifteen fusion transcript detection tools were compared using three synthetic data sets under different coverage, read length, insert size and background noise, and three real data sets with selected experimental validations. No single method dominantly performed the best but SOAPfuse generally performed well, followed by FusionCatcher and JAFFA. We further demonstrated the potential of a meta-caller algorithm by combining top performing methods to re-prioritize candidate fusion transcripts with high confidence that can be followed by experimental validation. Conclusion: Our result provides insightful recommendations when applying individual tool or combining top performers to identify fusion transcript candidates.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Topics: Biology
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    EMERGE: a flexible modelling framework to predict genomic regulatory elements from genomic signatures (2016)
    Oxford University Press
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    Publication Date: 2016-03-19
    Description: Regulatory DNA elements, short genomic segments that regulate gene expression, have been implicated in developmental disorders and human disease. Despite this clinical urgency, only a small fraction of the regulatory DNA repertoire has been confirmed through reporter gene assays. The overall success rate of functional validation of candidate regulatory elements is low. Moreover, the number and diversity of datasets from which putative regulatory elements can be identified is large and rapidly increasing. We generated a flexible and user-friendly tool to integrate the information from different types of genomic datasets, e.g. ATAC-seq, ChIP-seq, conservation, aiming to increase the ease and success rate of functional prediction. To this end, we developed the EMERGE program that merges all datasets that the user considers informative and uses a logistic regression framework, based on validated functional elements, to set optimal weights to these datasets. ROC curve analysis shows that a combination of datasets leads to improved prediction of tissue-specific enhancers in human, mouse and Drosophila genomes. Functional assays based on this prediction can be expected to have substantially higher success rates. The resulting integrated signal for prediction of functional elements can be plotted in a build-in genome browser or exported for further analysis.
    Keywords: Computational Methods, Genomics
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    Modeling co-occupancy of transcription factors using chromatin features (2016)
    Oxford University Press
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    Publication Date: 2016-03-19
    Description: Regulation of gene expression requires both transcription factor (TFs) and epigenetic modifications, and interplays between the two types of factors have been discovered. However study of relationships between chromatin features and TF–TF co-occupancy remains limited. Here, we revealed the relationship by first illustrating distinct profile patterns of chromatin features related to different binding events, including single TF binding and TF–TF co-occupancy of 71 TFs from five human cell lines. We further implemented statistical analyses to demonstrate the relationship by accurately predicting co-occupancy genome-widely using chromatin features including DNase I hypersensitivity, 11 histone modifications (HMs) and GC content. Remarkably, our results showed that the combination of chromatin features enables accurate predictions across the five cells. For individual chromatin features, DNase I enables high and consistent predictions. H3K27ac, H3K4me 2, H3K4me3 and H3K9ac are more reliable predictors than other HMs. Although the combination of 11 HMs achieves accurate predictions, their predictive ability varies considerably when a model obtained from one cell is applied to others, indicating relationship between HMs and TF–TF co-occupancy is cell type dependent. GC content is not a reliable predictor, but the addition of GC content to any other features enhances their predictive ability. Together, our results elucidate a strong relationship between TF–TF co-occupancy and chromatin features.
    Keywords: Computational Methods, Genomics
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    Discovering hotspots in functional genomic data superposed on 3D chromatin configuration reconstructions (2016)
    Oxford University Press
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    Publication Date: 2016-03-19
    Description: The spatial organization of the genome influences cellular function, notably gene regulation. Recent studies have assessed the three-dimensional (3D) co-localization of functional annotations (e.g. centromeres, long terminal repeats) using 3D genome reconstructions from Hi-C (genome-wide chromosome conformation capture) data; however, corresponding assessments for continuous functional genomic data (e.g. chromatin immunoprecipitation-sequencing (ChIP-seq) peak height) are lacking. Here, we demonstrate that applying bump hunting via the patient rule induction method (PRIM) to ChIP-seq data superposed on a Saccharomyces cerevisiae 3D genome reconstruction can discover ‘functional 3D hotspots’, regions in 3-space for which the mean ChIP-seq peak height is significantly elevated. For the transcription factor Swi6, the top hotspot by P -value contains MSB2 and ERG11 – known Swi6 target genes on different chromosomes. We verify this finding in a number of ways. First, this top hotspot is relatively stable under PRIM across parameter settings. Second, this hotspot is among the top hotspots by mean outcome identified by an alternative algorithm, k -Nearest Neighbor ( k -NN) regression. Third, the distance between MSB2 and ERG11 is smaller than expected (by resampling) in two other 3D reconstructions generated via different normalization and reconstruction algorithms. This analytic approach can discover functional 3D hotspots and potentially reveal novel regulatory interactions.
    Keywords: Computational Methods, Genomics
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    Simultaneous characterization of sense and antisense genomic processes by the double-stranded hidden Markov model (2016)
    Oxford University Press
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    Publication Date: 2016-03-19
    Description: Hidden Markov models (HMMs) have been extensively used to dissect the genome into functionally distinct regions using data such as RNA expression or DNA binding measurements. It is a challenge to disentangle processes occurring on complementary strands of the same genomic region. We present the double-stranded HMM (dsHMM), a model for the strand-specific analysis of genomic processes. We applied dsHMM to yeast using strand specific transcription data, nucleosome data, and protein binding data for a set of 11 factors associated with the regulation of transcription.The resulting annotation recovers the mRNA transcription cycle (initiation, elongation, termination) while correctly predicting strand-specificity and directionality of the transcription process. We find that pre-initiation complex formation is an essentially undirected process, giving rise to a large number of bidirectional promoters and to pervasive antisense transcription. Notably, 12% of all transcriptionally active positions showed simultaneous activity on both strands. Furthermore, dsHMM reveals that antisense transcription is specifically suppressed by Nrd1, a yeast termination factor.
    Keywords: Computational Methods, Genomics
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    csaw: a Bioconductor package for differential binding analysis of ChIP-seq data using sliding windows (2016)
    Oxford University Press
    Details
    Publication Date: 2016-03-19
    Description: Chromatin immunoprecipitation with massively parallel sequencing (ChIP-seq) is widely used to identify binding sites for a target protein in the genome. An important scientific application is to identify changes in protein binding between different treatment conditions, i.e. to detect differential binding. This can reveal potential mechanisms through which changes in binding may contribute to the treatment effect. The csaw package provides a framework for the de novo detection of differentially bound genomic regions. It uses a window-based strategy to summarize read counts across the genome. It exploits existing statistical software to test for significant differences in each window. Finally, it clusters windows into regions for output and controls the false discovery rate properly over all detected regions. The csaw package can handle arbitrarily complex experimental designs involving biological replicates. It can be applied to both transcription factor and histone mark datasets, and, more generally, to any type of sequencing data measuring genomic coverage. csaw performs favorably against existing methods for de novo DB analyses on both simulated and real data. csaw is implemented as a R software package and is freely available from the open-source Bioconductor project.
    Keywords: Computational Methods, Genomics
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    Estimate of within population incremental selection through branch imbalance in lineage trees (2016)
    Oxford University Press
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    Publication Date: 2016-03-19
    Description: Incremental selection within a population, defined as limited fitness changes following mutation, is an important aspect of many evolutionary processes. Strongly advantageous or deleterious mutations are detected using the synonymous to non-synonymous mutations ratio. However, there are currently no precise methods to estimate incremental selection. We here provide for the first time such a detailed method and show its precision in multiple cases of micro-evolution. The proposed method is a novel mixed lineage tree/sequence based method to detect within population selection as defined by the effect of mutations on the average number of offspring. Specifically, we propose to measure the log of the ratio between the number of leaves in lineage trees branches following synonymous and non-synonymous mutations. The method requires a high enough number of sequences, and a large enough number of independent mutations. It assumes that all mutations are independent events. It does not require of a baseline model and is practically not affected by sampling biases. We show the method's wide applicability by testing it on multiple cases of micro-evolution. We show that it can detect genes and inter-genic regions using the selection rate and detect selection pressures in viral proteins and in the immune response to pathogens.
    Keywords: Computational Methods, Genomics
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    COSMOS: accurate detection of somatic structural variations through asymmetric comparison between tumor and normal samples (2016)
    Oxford University Press
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    Publication Date: 2016-05-06
    Description: An important challenge in cancer genomics is precise detection of structural variations (SVs) by high-throughput short-read sequencing, which is hampered by the high false discovery rates of existing analysis tools. Here, we propose an accurate SV detection method named COSMOS, which compares the statistics of the mapped read pairs in tumor samples with isogenic normal control samples in a distinct asymmetric manner. COSMOS also prioritizes the candidate SVs using strand-specific read-depth information. Performance tests on modeled tumor genomes revealed that COSMOS outperformed existing methods in terms of F-measure. We also applied COSMOS to an experimental mouse cell-based model, in which SVs were induced by genome engineering and gamma-ray irradiation, followed by polymerase chain reaction-based confirmation. The precision of COSMOS was 84.5%, while the next best existing method was 70.4%. Moreover, the sensitivity of COSMOS was the highest, indicating that COSMOS has great potential for cancer genome analysis.
    Keywords: Computational Methods, Genomics
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    The Effect of the Fresh Fruit and Vegetable Program on Childhood Obesity (2016)
    Oxford University Press
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    Publication Date: 2016-05-19
    Description: This paper investigates how the Fresh Fruit and Vegetable Program (FFVP), a nutrition assistance program that provides funding for the distribution of free fresh fruits and vegetables to students in participating schools, affects childhood obesity using a panel data set of Arkansas public schoolchildren with two different approaches. First, we combine matching methodology and difference-in-differences (DID) analysis. Second, we use the synthetic control method to compare each FFVP participating school to a similar, albeit synthetic, control school. Both analyses show that FFVP program causes an economically meaningful reduction in the obesity outcome of participating children.
    Keywords: 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
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    Dynamics of Farmland Ownership and Leasing: Implications for Young and Beginning Farmers (2016)
    Oxford University Press
    Details
    Publication Date: 2016-05-19
    Description: This study considers the transition into farming and growth of new farmers in U.S. agriculture by examining land ownership and leasing trends. Our approach is to characterize the entire distribution by farmer age and farmer experience rather than using young versus old and beginning versus established farmer categories. We also use a linked-farms longitudinal approach to show trends over time in farmland expansion and contraction. We find that farms operated by older beginning farmers tend to be smaller and do not tend to grow over time. Our results show that it is mostly young farmers as opposed to all beginning farmers who rapidly expand their farm operations after entering agriculture. Our findings inform policy makers about the strategies that young and beginning farmers use to start their businesses and expand over time, and suggest more effective approaches for targeting loan programs to both young and beginning farmers.
    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: 2040-5790
    Electronic ISSN: 2040-5804
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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    The Economy-wide Impacts and Risks of Malawi's Farm Input Subsidy Program (2016)
    Oxford University Press
    Details
    Publication Date: 2016-04-24
    Description: We estimate the impact of Malawi's Farm Input Subsidy Program using an economy-wide approach. This approach yields benefit-cost ratios about 60% higher than existing partial equilibrium studies, a result of our accounting for indirect benefits. Fertilizer response rates remain the determining parameter for benefit-cost ratio levels. Even with lower-end response rates, the program is pro-poor and generates double-dividends through higher and more drought-resilient yields. Overall, for macro-economically significant programs, our approach strongly complements survey-based evaluations. For Malawi, our results buttress arguments for a focus on program improvements.
    Keywords: C68 - Computable General Equilibrium Models, O13 - Agriculture ; Natural Resources ; Energy ; Environment ; Other Primary Products, O22 - Project Analysis, 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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    Modeling the Market and Welfare Effects of Mexico's "Agriculture by Contract" Program (2016)
    Oxford University Press
    Details
    Publication Date: 2016-04-24
    Description: "Agriculture by contract" ( $\hbox {A}\times \hbox {C}$ ) is the main Mexican government program aimed at mitigating price risks for agricultural producers in Mexico. $\hbox {A} \times \hbox {C}$ has unique features involving forward contracts and the provision of basis subsidies and subsidized exchange-traded futures options for both producers and intermediaries. A simulation model is developed to analyze the market and welfare effects of $\hbox {A}\times \hbox {C}$ . When applied to corn, results show that $\hbox {A}\times \hbox {C}$ exerts substantial impacts and causes large transfers across sectors. Even if $\hbox {A}\times \hbox {C}$ reduced intermediaries' market power to the largest extent feasible, results indicate that it would still cause important losses in aggregate welfare.
    Keywords: Q11 - Aggregate Supply and Demand Analysis ; Prices, 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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    Bayesian Estimation of Possibly Similar Yield Densities: Implications for Rating Crop Insurance Contracts (2016)
    Oxford University Press
    Details
    Publication Date: 2016-03-31
    Description: The Agricultural Act of 2014 solidified insurance as the cornerstone of U.S. agricultural policy. The Congressional Budget Office (2014) estimates that this act will increase spending on agricultural insurance programs by $5.7 billion to a total of $89.8 billion over the next decade. In light of the sizable resources directed toward these programs, accurate rating of insurance contracts is of the utmost importance to producers, private insurance companies, and the federal government. Unlike most forms of insurance, agricultural insurance is plagued by a paucity of spatially correlated data. A novel interpretation of Bayesian Model Averaging is used to estimate a set of possibly similar densities that offers greater efficiency if the set of densities are similar while seemingly not losing any if the set of densities are dissimilar. Simulations indicate that finite sample performance—in particular small sample performance—is quite promising. The proposed approach does not require knowledge of the form or extent of any possible similarities, is relatively easy to implement, admits correlated data, and can be used with either parametric or nonparametric estimators. We use the proposed approach to estimate U.S. crop insurance premium rates for area-type programs and develop a test to evaluate its efficacy. An out-of-sample game between private insurance companies and the federal government highlights the policy implications for a variety of crop-state combinations. Consistent with the simulation results, the performance of the proposed approach with respect to rating area-type insurance—in particular small sample performance—remains quite promising.
    Keywords: 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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    How Healthy Is Hunger Relief Food? (2016)
    Oxford University Press
    Details
    Publication Date: 2016-03-31
    Description: Distributing healthy food is an important goal for hunger relief agencies, but they face many challenges in meeting it. Budgets for purchasing food are limited, and hunger relief agencies often have little influence over the nutritional quality of food they receive through donations. In a recent study, Healthy Eating Index (HEI) scores were calculated monthly using electronic invoice data for food shelves served by two major food banks in Minnesota. While the HEI is directly related to nutrition guidelines and provides great detail in its scoring, implementation requires careful measurement and classification of foods and a rather complex set of calculations. In addition, a significant portion of food distributed by food banks is mixed pallets of free "miscellaneous" that cannot readily be included in HEI calculations. We propose and test a less data- and labor-intensive measure for characterizing the healthfulness of food distributed by hunger relief agencies. This new measure, the Hunger Relief Nutrition Index (HRNI), facilitates nutritional assessment of miscellaneous foods, allows for easy aggregation of healthfulness scores across food sources and time periods, and correlates well with the HEI.
    Keywords: C81 - Methodology for Collecting, Estimating, and Organizing Microeconomic Data, 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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    Improving Food Bank Gleaning Operations: An Application in New York State (2016)
    Oxford University Press
    Details
    Publication Date: 2016-03-31
    Description: Gleaning is increasingly attracting the attention of food safety networks, including food banks, as a valuable tool that simultaneously reduces food loss and alleviates food insecurity. However, managing gleaning operations can be challenging because the arrival of gleaning opportunities and the attendance of gleaner volunteers are both stochastic. We develop a stochastic optimization model to characterize and optimize a gleaning operation. The food bank chooses the gleaning schedule, which affects the gleaner capacity and the number of gleaning opportunities scheduled. In a specific field study of the Food Bank of the Southern Tier in New York, we analyze the tradeoff between call and volume service levels to find the optimum schedule that maximizes the expected total volume gleaned. Moreover, we find that increasing the gleaning window and increasing slot availability can be used as substitute mechanisms for increasing the total volume gleaned. Additionally, we use our model to assess the impact of recruiting more volunteer gleaners.
    Keywords: C61 - Optimization Techniques ; Programming Models ; Dynamic Analysis, C63 - Computational Techniques, D24 - Production ; Cost ; Capital and Total Factor Productivity ; Capacity, 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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    Prioritizing and selecting likely novel miRNAs from NGS data (2016)
    Oxford University Press
    Details
    Publication Date: 2016-04-08
    Description: Small non-coding RNAs play a key role in many physiological and pathological processes. Since 2004, miRNA sequences have been catalogued in miRBase, which is currently in its 21st version. We investigated sequence and structural features of miRNAs annotated in the miRBase and compared them between different versions of this reference database. We have identified that the two most recent releases (v20 and v21) are influenced by next-generation sequencing based miRNA predictions and show significant deviation from miRNAs discovered prior to the high-throughput profiling period. From the analysis of miRBase, we derived a set of key characteristics to predict new miRNAs and applied the implemented algorithm to evaluate novel blood-borne miRNA candidates. We carried out 705 individual whole miRNA sequencings of blood cells and collected a total of 9.7 billion reads. Using miRDeep2 we initially predicted 1452 potentially novel miRNAs. After excluding false positives, 518 candidates remained. These novel candidates were ranked according to their distance to the features in the early miRBase versions allowing for an easier selection of a subset of putative miRNAs for validation. Selected candidates were successfully validated by qRT-PCR and northern blotting. In addition, we implemented a web-server for ranking potential miRNA candidates, which is available at: www.ccb.uni-saarland.de/novomirank .
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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    Gene integrated set profile analysis: a context-based approach for inferring biological endpoints (2016)
    Oxford University Press
    Details
    Publication Date: 2016-04-21
    Description: The identification of genes with specific patterns of change (e.g. down-regulated and methylated) as phenotype drivers or samples with similar profiles for a given gene set as drivers of clinical outcome, requires the integration of several genomic data types for which an ‘integrate by intersection’ (IBI) approach is often applied. In this approach, results from separate analyses of each data type are intersected, which has the limitation of a smaller intersection with more data types. We introduce a new method, GISPA (Gene Integrated Set Profile Analysis) for integrated genomic analysis and its variation, SISPA (Sample Integrated Set Profile Analysis) for defining respective genes and samples with the context of similar, a priori specified molecular profiles. With GISPA, the user defines a molecular profile that is compared among several classes and obtains ranked gene sets that satisfy the profile as drivers of each class. With SISPA, the user defines a gene set that satisfies a profile and obtains sample groups of profile activity. Our results from applying GISPA to human multiple myeloma (MM) cell lines contained genes of known profiles and importance, along with several novel targets, and their further SISPA application to MM coMMpass trial data showed clinical relevance.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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    CrossHub: a tool for multi-way analysis of The Cancer Genome Atlas (TCGA) in the context of gene expression regulation mechanisms (2016)
    Oxford University Press
    Details
    Publication Date: 2016-04-21
    Description: The contribution of different mechanisms to the regulation of gene expression varies for different tissues and tumors. Complementation of predicted mRNA–miRNA and gene–transcription factor (TF) relationships with the results of expression correlation analyses derived for specific tumor types outlines the interactions with functional impact in the current biomaterial. We developed CrossHub software, which enables two-way identification of most possible TF–gene interactions: on the basis of ENCODE ChIP-Seq binding evidence or Jaspar prediction and co-expression according to the data of The Cancer Genome Atlas (TCGA) project, the largest cancer omics resource. Similarly, CrossHub identifies mRNA–miRNA pairs with predicted or validated binding sites (TargetScan, mirSVR, PicTar, DIANA microT, miRTarBase) and strong negative expression correlations. We observed partial consistency between ChIP-Seq or miRNA target predictions and gene–TF/miRNA co-expression, demonstrating a link between these indicators. Additionally, CrossHub expression-methylation correlation analysis can be used to identify hypermethylated CpG sites or regions with the greatest potential impact on gene expression. Thus, CrossHub is capable of outlining molecular portraits of a specific gene and determining the three most common sources of expression regulation: promoter/enhancer methylation, miRNA interference and TF-mediated activation or repression. CrossHub generates formatted Excel workbooks with the detailed results. CrossHub is freely available at https://sourceforge.net/projects/crosshub/ .
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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    Revisiting the "Cash versus Food" Debate: New Evidence for an Old Puzzle? (2016)
    Oxford University Press
    Details
    Publication Date: 2016-02-10
    Description: The longstanding "cash versus food" debate has received renewed attention in both research and practice. This paper reviews key issues shaping the debate and presents new evidence from randomized and quasi-experimental evaluations that deliberately compare cash and in-kind food transfers in ten developing counties. Findings show that relative effectiveness cannot be generalized: although some differences emerge in terms of food consumption and dietary diversity, average impacts tend to depend on context, specific objectives, their measurement, and program design. Costs for cash transfers and vouchers tend to be significantly lower relative to in-kind food. Yet the consistency and robustness of methods for efficiency analyses varies greatly.
    Keywords: D61 - Allocative Efficiency ; Cost-Benefit Analysis, H53 - Government Expenditures and Welfare Programs, O12 - Microeconomic Analyses of Economic Development, O13 - Agriculture ; Natural Resources ; Energy ; Environment ; Other Primary Products, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0257-3032
    Electronic ISSN: 1564-6971
    Topics: Economics
    Published by Oxford University Press
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    Producer Insurance and Risk Management Options for Smallholder Farmers (2016)
    Oxford University Press
    Details
    Publication Date: 2016-10-28
    Description: Many smallholder families are exceptionally prone to potentially catastrophic decreases in their incomes and access to food. Over the past decade, therefore, policy makers and economists have increasingly focused on potential mechanisms for expanding risk management strategies available to those families. Commercially provided weather-based index insurance products, perhaps partially funded by subsidies, have been of particular interest because of their apparent potential to provide payments to smallholder families when they are most in need of help. However, the empirical evidence from a wide range of studies indicates that, absent relatively substantial subsidies, small holder farmers will not purchase commercially priced index products or even "all risk" products where payments are tied to the farm's crop losses. There are three important reasons why this is the case. First, smallholder farmers already have many ways of managing their risks, including informal community-based initiatives, on-farm production decisions and off-farm work. Second, index insurance schemes are subject to considerable basis risk; families often do not receive an index insurance indemnity when they experience a substantial crop loss on their farms. Third, the fixed costs of delivering crop insurance to smallholders make such coverage expensive. The potential market for weather index insurance therefore may be limited to insuring relatively large groups of farmers, either directly or indirectly though providing micro finance and other lending institution with coverage against widespread loan defaults associated with catastrophic events like major droughts. Alternatively, weather indexes could simply be used to more accurately target emergency aid.
    Keywords: D61 - Allocative Efficiency ; Cost-Benefit Analysis, O13 - Agriculture ; Natural Resources ; Energy ; Environment ; Other Primary Products, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0257-3032
    Electronic ISSN: 1564-6971
    Topics: Economics
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    Effects of U.S. Public Agricultural R&D on U.S. Obesity and its Social Costs (2016)
    Oxford University Press
    Details
    Publication Date: 2016-08-20
    Description: How much has food abundance, attributable to U.S. public agricultural R&D, contributed to high and rising U.S. obesity rates? In this paper we investigate the effects of public investment in agricultural R&D on food prices, per capita calorie consumption, adult body weight, obesity, public healthcare expenditures related to obesity, and consumer welfare. We find that a 10% increase in the stream of annual U.S. public investment in agricultural R&D in the latter half of the twentieth century would have caused a modest increase in the average daily calorie consumption of American adults, resulting in small increases in public healthcare expenditures related to obesity. On the other hand, such an increase in spending would have generated very substantial consumer benefits, and net national benefits, given the very large benefit-cost ratios for agricultural R&D. This implies that current policy objectives of revising agricultural R&D priorities to pursue obesity objectives are likely to be comparatively unproductive and socially wasteful. Moreover, R&D lags of decades mean that such an approach would be totally ineffective in the immediate horizon.
    Keywords: I18 - Government Policy ; Regulation ; Public Health, Q16 - R&D ; Agricultural Technology ; Agricultural Extension Services, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 2040-5790
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    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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    Robust lineage reconstruction from high-dimensional single-cell data (2016)
    Oxford University Press
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    Publication Date: 2016-08-20
    Description: Single-cell gene expression data provide invaluable resources for systematic characterization of cellular hierarchy in multi-cellular organisms. However, cell lineage reconstruction is still often associated with significant uncertainty due to technological constraints. Such uncertainties have not been taken into account in current methods. We present ECLAIR (Ensemble Cell Lineage Analysis with Improved Robustness), a novel computational method for the statistical inference of cell lineage relationships from single-cell gene expression data. ECLAIR uses an ensemble approach to improve the robustness of lineage predictions, and provides a quantitative estimate of the uncertainty of lineage branchings. We show that the application of ECLAIR to published datasets successfully reconstructs known lineage relationships and significantly improves the robustness of predictions. ECLAIR is a powerful bioinformatics tool for single-cell data analysis. It can be used for robust lineage reconstruction with quantitative estimate of prediction accuracy.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Topics: Biology
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    The exon quantification pipeline (EQP): a comprehensive approach to the quantification of gene, exon and junction expression from RNA-seq data (2016)
    Oxford University Press
    Details
    Publication Date: 2016-09-20
    Description: The quantification of transcriptomic features is the basis of the analysis of RNA-seq data. We present an integrated alignment workflow and a simple counting-based approach to derive estimates for gene, exon and exon–exon junction expression. In contrast to previous counting-based approaches, EQP takes into account only reads whose alignment pattern agrees with the splicing pattern of the features of interest. This leads to improved gene expression estimates as well as to the generation of exon counts that allow disambiguating reads between overlapping exons. Unlike other methods that quantify skipped introns, EQP offers a novel way to compute junction counts based on the agreement of the read alignments with the exons on both sides of the junction, thus providing a uniformly derived set of counts. We evaluated the performance of EQP on both simulated and real Illumina RNA-seq data and compared it with other quantification tools. Our results suggest that EQP provides superior gene expression estimates and we illustrate the advantages of EQP's exon and junction counts. The provision of uniformly derived high-quality counts makes EQP an ideal quantification tool for differential expression and differential splicing studies. EQP is freely available for download at https://github.com/Novartis/EQP-cluster .
    Keywords: Computational Methods, Genomics
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    Topics: Biology
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    Boiler: lossy compression of RNA-seq alignments using coverage vectors (2016)
    Oxford University Press
    Details
    Publication Date: 2016-09-20
    Description: We describe Boiler, a new software tool for compressing and querying large collections of RNA-seq alignments. Boiler discards most per-read data, keeping only a genomic coverage vector plus a few empirical distributions summarizing the alignments. Since most per-read data is discarded, storage footprint is often much smaller than that achieved by other compression tools. Despite this, the most relevant per-read data can be recovered; we show that Boiler compression has only a slight negative impact on results given by downstream tools for isoform assembly and quantification. Boiler also allows the user to pose fast and useful queries without decompressing the entire file. Boiler is free open source software available from github.com/jpritt/boiler .
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Topics: Biology
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    Global transcript structure resolution of high gene density genomes through multi-platform data integration (2016)
    Oxford University Press
    Details
    Publication Date: 2016-10-14
    Description: Annotation of herpesvirus genomes has traditionally been undertaken through the detection of open reading frames and other genomic motifs, supplemented with sequencing of individual cDNAs. Second generation sequencing and high-density microarray studies have revealed vastly greater herpesvirus transcriptome complexity than is captured by existing annotation. The pervasive nature of overlapping transcription throughout herpesvirus genomes, however, poses substantial problems in resolving transcript structures using these methods alone. We present an approach that combines the unique attributes of Pacific Biosciences Iso-Seq long-read, Illumina short-read and deepCAGE (Cap Analysis of Gene Expression) sequencing to globally resolve polyadenylated isoform structures in replicating Epstein-Barr virus (EBV). Our method, Transcriptome Resolution through Integration of Multi-platform Data (TRIMD), identifies nearly 300 novel EBV transcripts, quadrupling the size of the annotated viral transcriptome. These findings illustrate an array of mechanisms through which EBV achieves functional diversity in its relatively small, compact genome including programmed alternative splicing (e.g. across the IR1 repeats), alternative promoter usage by LMP2 and other latency-associated transcripts, intergenic splicing at the BZLF2 locus, and antisense transcription and pervasive readthrough transcription throughout the genome.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Topics: Biology
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    Identification of multi-loci hubs from 4C-seq demonstrates the functional importance of simultaneous interactions (2016)
    Oxford University Press
    Details
    Publication Date: 2016-10-14
    Description: Use of low resolution single cell DNA FISH and population based high resolution chromosome conformation capture techniques have highlighted the importance of pairwise chromatin interactions in gene regulation. However, it is unlikely that associations involving regulatory elements act in isolation of other interacting partners that also influence their impact. Indeed, the influence of multi-loci interactions remains something of an enigma as beyond low-resolution DNA FISH we do not have the appropriate tools to analyze these. Here we present a method that uses standard 4C-seq data to identify multi-loci interactions from the same cell. We demonstrate the feasibility of our method using 4C-seq data sets that identify known pairwise and novel tri-loci interactions involving the Tcrb and Igk antigen receptor enhancers. We further show that the three Igk enhancers, MiE, 3'E and Ed, interact simultaneously in this super-enhancer cluster, which add to our previous findings showing that loss of one element decreases interactions between all three elements as well as reducing their transcriptional output. These findings underscore the functional importance of simultaneous interactions and provide new insight into the relationship between enhancer elements. Our method opens the door for studying multi-loci interactions and their impact on gene regulation in other biological settings.
    Keywords: Computational Methods, Genomics
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    Topics: Biology
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    Identify bilayer modules via pseudo-3D clustering: applications to miRNA-gene bilayer networks (2016)
    Oxford University Press
    Details
    Publication Date: 2016-12-01
    Description: Module identification is a frequently used approach for mining local structures with more significance in global networks. Recently, a wide variety of bilayer networks are emerging to characterize the more complex biological processes. In the light of special topological properties of bilayer networks and the accompanying challenges, there is yet no effective method aiming at bilayer module identification to probe the modular organizations from the more inspiring bilayer networks. To this end, we proposed the pseudo-3D clustering algorithm, which starts from extracting initial non-hierarchically organized modules and then iteratively deciphers the hierarchical organization of modules according to a bottom-up strategy. Specifically, a modularity function for bilayer modules was proposed to facilitate the algorithm reporting the optimal partition that gives the most accurate characterization of the bilayer network. Simulation studies demonstrated its robustness and outperformance against alternative competing methods. Specific applications to both the soybean and human miRNA-gene bilayer networks demonstrated that the pseudo-3D clustering algorithm successfully identified the overlapping, hierarchically organized and highly cohesive bilayer modules. The analyses on topology, functional and human disease enrichment and the bilayer subnetwork involved in soybean fat biosynthesis provided both the theoretical and biological evidence supporting the effectiveness and robustness of pseudo-3D clustering algorithm.
    Keywords: Computational Methods, Genomics
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    Topics: Biology
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    Finding approximate gene clusters with GECKO 3 (2016)
    Oxford University Press
    Details
    Publication Date: 2016-12-01
    Description: Gene-order-based comparison of multiple genomes provides signals for functional analysis of genes and the evolutionary process of genome organization. Gene clusters are regions of co-localized genes on genomes of different species. The rapid increase in sequenced genomes necessitates bioinformatics tools for finding gene clusters in hundreds of genomes. Existing tools are often restricted to few (in many cases, only two) genomes, and often make restrictive assumptions such as short perfect conservation, conserved gene order or monophyletic gene clusters. We present Gecko 3, an open-source software for finding gene clusters in hundreds of bacterial genomes, that comes with an easy-to-use graphical user interface. The underlying gene cluster model is intuitive, can cope with low degrees of conservation as well as misannotations and is complemented by a sound statistical evaluation. To evaluate the biological benefit of Gecko 3 and to exemplify our method, we search for gene clusters in a dataset of 678 bacterial genomes using Synechocystis sp. PCC 6803 as a reference. We confirm detected gene clusters reviewing the literature and comparing them to a database of operons; we detect two novel clusters, which were confirmed by publicly available experimental RNA-Seq data. The computational analysis is carried out on a laptop computer in 〈40 min.
    Keywords: Computational Methods, Genomics
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    Explaining the Impact of USDA's Healthy Incentives Pilot on Different Spending Outcomes (2016)
    Oxford University Press
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    Publication Date: 2016-12-07
    Description: This article reports spending results for the USDA's Healthy Incentives Pilot (HIP), which tested a 30% incentive on fruit and vegetable purchases with Supplemental Nutrition Assistance Program (SNAP) benefits. Self-reported mean usual monthly spending for all fruits and vegetables was $6.15 higher for randomly assigned HIP participant households than for a control group. Much of the additional spending appears to have taken place in ways that did not earn the incentive—spending with non-SNAP resources or in retailers that did not participate in HIP. This article investigates mechanisms that might explain the HIP impact on fruit and vegetable purchases that did not earn the incentive.
    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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    DynaMIT: the dynamic motif integration toolkit (2016)
    Oxford University Press
    Details
    Publication Date: 2016-01-09
    Description: De-novo motif search is a frequently applied bioinformatics procedure to identify and prioritize recurrent elements in sequences sets for biological investigation, such as the ones derived from high-throughput differential expression experiments. Several algorithms have been developed to perform motif search, employing widely different approaches and often giving divergent results. In order to maximize the power of these investigations and ultimately be able to draft solid biological hypotheses, there is the need for applying multiple tools on the same sequences and merge the obtained results. However, motif reporting formats and statistical evaluation methods currently make such an integration task difficult to perform and mostly restricted to specific scenarios. We thus introduce here the Dynamic Motif Integration Toolkit (DynaMIT), an extremely flexible platform allowing to identify motifs employing multiple algorithms, integrate them by means of a user-selected strategy and visualize results in several ways; furthermore, the platform is user-extendible in all its aspects. DynaMIT is freely available at http://cibioltg.bitbucket.org .
    Keywords: Computational Methods, Genomics
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    Topics: Biology
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    Large-scale profiling of microRNAs for The Cancer Genome Atlas (2016)
    Oxford University Press
    Details
    Publication Date: 2016-01-09
    Description: The comprehensive multiplatform genomics data generated by The Cancer Genome Atlas (TCGA) Research Network is an enabling resource for cancer research. It includes an unprecedented amount of microRNA sequence data: ~11 000 libraries across 33 cancer types. Combined with initiatives like the National Cancer Institute Genomics Cloud Pilots, such data resources will make intensive analysis of large-scale cancer genomics data widely accessible. To support such initiatives, and to enable comparison of TCGA microRNA data to data from other projects, we describe the process that we developed and used to generate the microRNA sequence data, from library construction through to submission of data to repositories. In the context of this process, we describe the computational pipeline that we used to characterize microRNA expression across large patient cohorts.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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    MethylAction: detecting differentially methylated regions that distinguish biological subtypes (2016)
    Oxford University Press
    Details
    Publication Date: 2016-01-09
    Description: DNA methylation differences capture substantial information about the molecular and gene-regulatory states among biological subtypes. Enrichment-based next generation sequencing methods such as MBD-isolated genome sequencing (MiGS) and MeDIP-seq are appealing for studying DNA methylation genome-wide in order to distinguish between biological subtypes. However, current analytic tools do not provide optimal features for analyzing three-group or larger study designs. MethylAction addresses this need by detecting all possible patterns of statistically significant hyper- and hypo- methylation in comparisons involving any number of groups. Crucially, significance is established at the level of differentially methylated regions (DMRs), and bootstrapping determines false discovery rates (FDRs) associated with each pattern. We demonstrate this functionality in a four-group comparison among benign prostate and three clinical subtypes of prostate cancer and show that the bootstrap FDRs are highly useful in selecting the most robust patterns of DMRs. Compared to existing tools that are limited to two-group comparisons, MethylAction detects more DMRs with strong differential methylation measurements confirmed by whole genome bisulfite sequencing and offers a better balance between precision and recall in cross-cohort comparisons. MethylAction is available as an R package at http://jeffbhasin.github.io/methylaction .
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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    NanoStringDiff: a novel statistical method for differential expression analysis based on NanoString nCounter data (2016)
    Oxford University Press
    Details
    Publication Date: 2016-12-01
    Description: The advanced medium-throughput NanoString nCounter technology has been increasingly used for mRNA or miRNA differential expression (DE) studies due to its advantages including direct measurement of molecule expression levels without amplification, digital readout and superior applicability to formalin fixed paraffin embedded samples. However, the analysis of nCounter data is hampered because most methods developed are based on t-tests, which do not fit the count data generated by the NanoString nCounter system. Furthermore, data normalization procedures of current methods are either not suitable for counts or not specific for NanoString nCounter data. We develop a novel DE detection method based on NanoString nCounter data. The method, named NanoStringDiff, considers a generalized linear model of the negative binomial family to characterize count data and allows for multifactor design. Data normalization is incorporated in the model framework through data normalization parameters, which are estimated from positive controls, negative controls and housekeeping genes embedded in the nCounter system. We propose an empirical Bayes shrinkage approach to estimate the dispersion parameter in the model and a likelihood ratio test to identify differentially expressed genes. Simulations and real data analysis demonstrate that the proposed method performs better than existing methods.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
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    Topics: Biology
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    Did Revisions to the WIC Program Affect Household Expenditures on Whole Grains? (2016)
    Oxford University Press
    Details
    Publication Date: 2016-12-07
    Description: The food packages provided by the Supplemental Nutrition Program for Women, Infants, and Children (WIC) program changed in 2009. This article examines purchases of whole grain products before and after the change. Nielsen Homescan panel data from 2008 to 2010 provide information on households’ food purchases, demographics, and self-reported WIC participation status. We estimate the effect of WIC participation and the 2009 package change on whole grains purchases using a difference-in-difference method, and find that participation in the WIC program was associated with more whole grain purchases during the observed period; the package change in 2009 roughly doubled the associated effect of WIC participation on the purchases of whole grain products. These results are consistent with recommendations in the Dietary Guidelines for Americans and suggest that moderate innovations in the design of food assistance programs can lead to beneficial dietary choices.
    Keywords: D10 - General, 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
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    How Meat Demand Elasticities Vary with Price, Income, and Product Category (2016)
    Oxford University Press
    Details
    Publication Date: 2016-12-07
    Description: As US beef and pork prices approached record high levels in 2014, industry analysts expressed surprised at consumer response. Because the relative price swings have occurred only recently, traditional approaches to demand analysis that rely on historical data series may be less useful than is typically the case. Employing one of the largest and longest-running choice experiments, we analyze data on 110,295 choices made by 12,255 consumers observed over a year-long time period coinciding with historically high meat prices. Our findings reveal nonlinear demands for meat products, with demand being more inelastic at higher prices. Ground beef, steak, and pork chop demands are more sensitive to changes in chicken breast price than the reverse. Moreover, cross-price elasticities between disaggregate meat products shrink as prices rise. Consumers' incomes significantly affect demand inter-relationships. Higher income consumers are more likely to choose steak and chicken breasts and are less likely to choose ground beef, chicken wings, and deli ham than are lower income consumers. High-income consumers tend to be less responsive to own-price changes and more responsive to cross-price changes than lower income consumers. This analysis provides estimates of structural demand parameters that help explain current meat expenditure patterns, and the results have implications for the assumption of linearity often invoked in policy analyses. 
    Keywords: C83 - Survey Methods ; Sampling Methods, D12 - Consumer Economics: Empirical Analysis, Q11 - Aggregate Supply and Demand Analysis ; Prices, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 2040-5790
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    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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    RNA2DNAlign: nucleotide resolution allele asymmetries through quantitative assessment of RNA and DNA paired sequencing data (2016)
    Oxford University Press
    Details
    Publication Date: 2016-12-17
    Description: We introduce RNA2DNAlign, a computational framework for quantitative assessment of allele counts across paired RNA and DNA sequencing datasets. RNA2DNAlign is based on quantitation of the relative abundance of variant and reference read counts, followed by binomial tests for genotype and allelic status at SNV positions between compatible sequences. RNA2DNAlign detects positions with differential allele distribution, suggesting asymmetries due to regulatory/structural events. Based on the type of asymmetry, RNA2DNAlign outlines positions likely to be implicated in RNA editing, allele-specific expression or loss, somatic mutagenesis or loss-of-heterozygosity (the first three also in a tumor-specific setting). We applied RNA2DNAlign on 360 matching normal and tumor exomes and transcriptomes from 90 breast cancer patients from TCGA. Under high-confidence settings, RNA2DNAlign identified 2038 distinct SNV sites associated with one of the aforementioned asymetries, the majority of which have not been linked to functionality before. The performance assessment shows very high specificity and sensitivity, due to the corroboration of signals across multiple matching datasets. RNA2DNAlign is freely available from http://github.com/HorvathLab/NGS as a self-contained binary package for 64-bit Linux systems.
    Keywords: Computational Methods, Genomics
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    Topics: Biology
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    Identifying gene regulatory network rewiring using latent differential graphical models (2016)
    Oxford University Press
    Details
    Publication Date: 2016-10-08
    Description: Gene regulatory networks (GRNs) are highly dynamic among different tissue types. Identifying tissue-specific gene regulation is critically important to understand gene function in a particular cellular context. Graphical models have been used to estimate GRN from gene expression data to distinguish direct interactions from indirect associations. However, most existing methods estimate GRN for a specific cell/tissue type or in a tissue-naive way, or do not specifically focus on network rewiring between different tissues. Here, we describe a new method called Latent Differential Graphical Model (LDGM). The motivation of our method is to estimate the differential network between two tissue types directly without inferring the network for individual tissues, which has the advantage of utilizing much smaller sample size to achieve reliable differential network estimation. Our simulation results demonstrated that LDGM consistently outperforms other Gaussian graphical model based methods. We further evaluated LDGM by applying to the brain and blood gene expression data from the GTEx consortium. We also applied LDGM to identify network rewiring between cancer subtypes using the TCGA breast cancer samples. Our results suggest that LDGM is an effective method to infer differential network using high-throughput gene expression data to identify GRN dynamics among different cellular conditions.
    Keywords: Computational Methods, Genomics
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    Topics: Biology
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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
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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
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    Topics: Biology
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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
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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
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    Topics: Biology
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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
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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
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    Topics: Biology
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    Reconstructing genome-scale metabolic models with merlin (2015)
    Oxford University Press
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    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
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    Inferential modeling of 3D chromatin structure (2015)
    Oxford University Press
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    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
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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
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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
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    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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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
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    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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    Decomposing the Farmer's Share of the Food Dollar (2015)
    Oxford University Press
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    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
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    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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    Food Insecurity and Food Access in U.S. Metropolitan Areas (2015)
    Oxford University Press
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    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
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    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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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
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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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    Why weight? Modelling sample and observational level variability improves power in RNA-seq analyses (2015)
    Oxford University Press
    Details
    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
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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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    Following Up on Smallholder Farmers and Supermarkets in Kenya (2015)
    Oxford University Press
    Details
    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
    Details
    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
    Details
    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
    Electronic ISSN: 1362-4962
    Topics: Biology
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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
    Details
    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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    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
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    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
    Details
    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
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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