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  • 1
    Publication Date: 2013-06-08
    Description: DNA methylation is a mechanism for long-term transcriptional regulation and is required for normal cellular differentiation. Failure to properly establish or maintain DNA methylation patterns leads to cell dysfunction and diseases such as cancer. Identifying DNA methylation signatures in complex tissues can be challenging owing to inaccurate cell enrichment methods and low DNA yields. We have developed a technique called laser capture microdissection-reduced representation bisulfite sequencing (LCM-RRBS) for the multiplexed interrogation of the DNA methylation status of cytosine–guanine dinucleotide islands and promoters. LCM-RRBS accurately and reproducibly profiles genome-wide methylation of DNA extracted from microdissected fresh frozen or formalin-fixed paraffin-embedded tissue samples. To demonstrate the utility of LCM-RRBS, we characterized changes in DNA methylation associated with gonadectomy-induced adrenocortical neoplasia in the mouse. Compared with adjacent normal tissue, the adrenocortical tumors showed reproducible gains and losses of DNA methylation at genes involved in cell differentiation and organ development. LCM-RRBS is a rapid, cost-effective, and sensitive technique for analyzing DNA methylation in heterogeneous tissues and will facilitate the investigation of DNA methylation in cancer and organ development.
    Keywords: Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 2
    Publication Date: 2014-12-17
    Description: The advent in high-throughput-sequencing (HTS) technologies has revolutionized conventional biodiversity research by enabling parallel capture of DNA sequences possessing species-level diagnosis. However, polymerase chain reaction (PCR)-based implementation is biased by the efficiency of primer binding across lineages of organisms. A PCR-free HTS approach will alleviate this artefact and significantly improve upon the multi-locus method utilizing full mitogenomes. Here we developed a novel multiplex sequencing and assembly pipeline allowing for simultaneous acquisition of full mitogenomes from pooled animals without DNA enrichment or amplification. By concatenating assemblies from three de novo assemblers, we obtained high-quality mitogenomes for all 49 pooled taxa, with 36 species 〉15 kb and the remaining 〉10 kb, including 20 complete mitogenomes and nearly all protein coding genes (99.6%). The assembly quality was carefully validated with Sanger sequences, reference genomes and conservativeness of protein coding genes across taxa. The new method was effective even for closely related taxa, e.g. three Drosophila spp., demonstrating its broad utility for biodiversity research and mito-phylogenomics. Finally, the in silico simulation showed that by recruiting multiple mito-loci, taxon detection was improved at a fixed sequencing depth. Combined, these results demonstrate the plausibility of a multi-locus mito-metagenomics approach as the next phase of the current single-locus metabarcoding method.
    Keywords: Genomics
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    Topics: Biology
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  • 3
    Publication Date: 2014-12-17
    Description: Chromatin modifiers and histone modifications are components of a chromatin-signaling network involved in transcription and its regulation. The interactions between chromatin modifiers and histone modifications are often unknown, are based on the analysis of few genes or are studied in vitro . Here, we apply computational methods to recover interactions between chromatin modifiers and histone modifications from genome-wide ChIP-Seq data. These interactions provide a high-confidence backbone of the chromatin-signaling network. Many recovered interactions have literature support; others provide hypotheses about yet unknown interactions. We experimentally verified two of these predicted interactions, leading to a link between H4K20me1 and members of the Polycomb Repressive Complexes 1 and 2. Our results suggest that our computationally derived interactions are likely to lead to novel biological insights required to establish the connectivity of the chromatin-signaling network involved in transcription and its regulation.
    Keywords: Genomics
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    Topics: Biology
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  • 4
    Publication Date: 2014-12-03
    Keywords: C91 - Laboratory, Individual Behavior, I18 - Government Policy ; Regulation ; Public Health
    Print ISSN: 2040-5790
    Electronic ISSN: 2040-5804
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 5
    Publication Date: 2011-11-24
    Description: In this paper, a modelling approach is developed for the treatment of ‘don't know’(DK) responses, within choice experiments (CEs). A DK option is motivated by the need to allow respondents the opportunity to express uncertainty. Our model explains a DK using an entropy measure of the similarity between options given to respondents within the CE. We illustrate our model by applying it to a CE examining consumer preferences for nutrient contents in food. We find that similarity between options in a given choice set does explain the tendency for respondents to report DK.
    Keywords: C35 - Discrete Regression and Qualitative Choice Models, I18 - Government Policy ; Regulation ; Public Health, 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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  • 6
    Publication Date: 2014-01-22
    Description: Using the 2007 National Survey of Children's Health data, we find a statistically and economically significant effect of neighborhood parks and playgrounds on childhood obesity based on covariate matching estimators. The park/playground effect depends on gender, age, race, household income, neighborhood safety, and other neighborhood amenities. The results suggest that adding a neighborhood park/playground may reduce the obesity rate and make children more fit, but relevant interventions must consider socioeconomic status of the targeted children as well as other neighborhood amenities.
    Keywords: I18 - Government Policy ; Regulation ; Public Health, I38 - Government Policy ; Provision and Effects of Welfare Programs, R53 - Public Facility Location Analysis ; Public Investment and Capital Stock
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 7
    Publication Date: 2013-12-07
    Description: Identity by descent (IBD) can be reliably detected for long shared DNA segments, which are found in related individuals. However, many studies contain cohorts of unrelated individuals that share only short IBD segments. New sequencing technologies facilitate identification of short IBD segments through rare variants, which convey more information on IBD than common variants. Current IBD detection methods, however, are not designed to use rare variants for the detection of short IBD segments. Short IBD segments reveal genetic structures at high resolution. Therefore, they can help to improve imputation and phasing, to increase genotyping accuracy for low-coverage sequencing and to increase the power of association studies. Since short IBD segments are further assumed to be old, they can shed light on the evolutionary history of humans. We propose HapFABIA, a computational method that applies biclustering to identify very short IBD segments characterized by rare variants. HapFABIA is designed to detect short IBD segments in genotype data that were obtained from next-generation sequencing, but can also be applied to DNA microarray data. Especially in next-generation sequencing data, HapFABIA exploits rare variants for IBD detection. HapFABIA significantly outperformed competing algorithms at detecting short IBD segments on artificial and simulated data with rare variants. HapFABIA identified 160 588 different short IBD segments characterized by rare variants with a median length of 23 kb (mean 24 kb) in data for chromosome 1 of the 1000 Genomes Project. These short IBD segments contain 752 000 single nucleotide variants (SNVs), which account for 39% of the rare variants and 23.5% of all variants. The vast majority—152 000 IBD segments—are shared by Africans, while only 19 000 and 11 000 are shared by Europeans and Asians, respectively. IBD segments that match the Denisova or the Neandertal genome are found significantly more often in Asians and Europeans but also, in some cases exclusively, in Africans. The lengths of IBD segments and their sharing between continental populations indicate that many short IBD segments from chromosome 1 existed before humans migrated out of Africa. Thus, rare variants that tag these short IBD segments predate human migration from Africa. The software package HapFABIA is available from Bioconductor. All data sets, result files and programs for data simulation, preprocessing and evaluation are supplied at http://www.bioinf.jku.at/research/short-IBD .
    Keywords: Genomics
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  • 8
    Publication Date: 2013-12-07
    Description: Glioma is the most common and fatal primary brain tumour with poor prognosis; however, the functional roles of miRNAs in glioma malignant progression are insufficiently understood. Here, we used an integrated approach to identify miRNA functional targets during glioma malignant progression by combining the paired expression profiles of miRNAs and mRNAs across 160 Chinese glioma patients, and further constructed the functional miRNA–mRNA regulatory network. As a result, most tumour-suppressive miRNAs in glioma progression were newly discovered, whose functions were widely involved in gliomagenesis. Moreover, three miRNA signatures, with different combinations of hub miRNAs (regulations≥30) were constructed, which could independently predict the survival of patients with all gliomas, high-grade glioma and glioblastoma. Our network-based method increased the ability to identify the prognostic biomarkers, when compared with the traditional method and random conditions. Hsa-miR-524-5p and hsa-miR-628-5p, shared by these three signatures, acted as protective factors and their expression decreased gradually during glioma progression. Functional analysis of these miRNA signatures highlighted their critical roles in cell cycle and cell proliferation in glioblastoma malignant progression, especially hsa-miR-524-5p and hsa-miR-628-5p exhibited dominant regulatory activities. Therefore, network-based biomarkers are expected to be more effective and provide deep insights into the molecular mechanism of glioma malignant progression.
    Keywords: Genomics
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    Topics: Biology
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  • 9
    Publication Date: 2014-03-21
    Description: The economic theory of regulatory capture predicts that industry groups will attempt to influence their regulators (for example, by lobbying for rules that exclude competition). It has been suggested that the same logic applies to any powerful institution with the ability to affect industry profits. When the aim of industry is to alter the public’s perception of its product (for example, by disseminating favorable messages to the news media or via an advertising campaign, or by funding industry-friendly scientific research), the end result has been dubbed deep capture. We develop a formal model of deep capture, in which consumers have imperfect information about product quality, and a dominant producer is able to increase his profits by altering the parameters of the consumer’s search problem. We demonstrate the empirical relevance of the phenomenon with a discussion of the food industry response to the obesity epidemic.
    Keywords: D18 - Consumer Protection, D83 - Search ; Learning ; Information and Knowledge ; Communication ; Belief, I18 - Government Policy ; Regulation ; Public Health, L15 - Information and Product Quality ; Standardization and Compatibility, L51 - Economics of Regulation
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 10
    Publication Date: 2014-02-11
    Description: A major challenge in cancer genomics is uncovering genes with an active role in tumorigenesis from a potentially large pool of mutated genes across patient samples. Here we focus on the interactions that proteins make with nucleic acids, small molecules, ions and peptides, and show that residues within proteins that are involved in these interactions are more frequently affected by mutations observed in large-scale cancer genomic data than are other residues. We leverage this observation to predict genes that play a functionally important role in cancers by introducing a computational pipeline ( http://canbind.princeton.edu ) for mapping large-scale cancer exome data across patients onto protein structures, and automatically extracting proteins with an enriched number of mutations affecting their nucleic acid, small molecule, ion or peptide binding sites. Using this computational approach, we show that many previously known genes implicated in cancers are enriched in mutations within the binding sites of their encoded proteins. By focusing on functionally relevant portions of proteins—specifically those known to be involved in molecular interactions—our approach is particularly well suited to detect infrequent mutations that may nonetheless be important in cancer, and should aid in expanding our functional understanding of the genomic landscape of cancer.
    Keywords: Genomics
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    Topics: Biology
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  • 11
    Publication Date: 2014-04-03
    Description: Genome duplication with hybridization, or allopolyploidization, occurs commonly in plants, and is considered to be a strong force for generating new species. However, genome-wide quantification of homeolog expression ratios was technically hindered because of the high homology between homeologous gene pairs. To quantify the homeolog expression ratio using RNA-seq obtained from polyploids, a new method named HomeoRoq was developed, in which the genomic origin of sequencing reads was estimated using mismatches between the read and each parental genome. To verify this method, we first assembled the two diploid parental genomes of Arabidopsis halleri subsp. gemmifera and Arabidopsis lyrata subsp. petraea ( Arabidopsis petraea subsp. umbrosa ), then generated a synthetic allotetraploid, mimicking the natural allopolyploid Arabidopsis kamchatica . The quantified ratios corresponded well to those obtained by Pyrosequencing. We found that the ratios of homeologs before and after cold stress treatment were highly correlated ( r = 0.870). This highlights the presence of nonstochastic polyploid gene regulation despite previous research identifying stochastic variation in expression. Moreover, our new statistical test incorporating overdispersion identified 226 homeologs (1.11% of 20 369 expressed homeologs) with significant ratio changes, many of which were related to stress responses. HomeoRoq would contribute to the study of the genes responsible for polyploid-specific environmental responses.
    Keywords: Genomics
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    Topics: Biology
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  • 12
    Publication Date: 2014-04-05
    Description: A substantial share of U.S. hog producers incorporate antimicrobial drugs into their livestock's feed or water at sub-therapeutic levels to promote feed efficiency and weight gain. Recently, in response to concerns that the overuse of antibiotics in livestock could promote the development of antimicrobial drug-resistant bacteria, the U.S. Food and Drug Administration adopted a strategy to phase out the use of antibiotics for production purposes. This study uses a stochastic frontier model and data from the 2009 USDA Agricultural Resource Management Survey of feeder-to-finish hog producers to estimate the potential effects on hog output and output variability resulting from a ban on antibiotics used for growth promotion. We use propensity score nearest neighbor matching to create a balanced sample of sub-therapeutic antibiotic (STA) users and nonusers. We estimate the frontier model for the pooled sample and separately for users and non-users—which allows for a flexible interaction between STA use and the production technology. Point estimates for the matched sample indicate that STA use has a small positive effect on productivity and production risk, increasing output by 1.0–1.3% and reducing the standard deviation of unexplained output by 1.4%. The results indicate that improvements in productivity resulted exclusively from technological improvement rather than from an increase in technical efficiency.
    Keywords: D24 - Production ; Cost ; Capital and Total Factor Productivity ; Capacity, I18 - Government Policy ; Regulation ; Public Health, 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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  • 13
    Publication Date: 2012-10-10
    Description: Enriching target sequences in sequencing libraries via capture hybridization to bait/probes is an efficient means of leveraging the capabilities of next-generation sequencing for obtaining sequence data from target regions of interest. However, homologous sequences from non-target regions may also be enriched by such methods. Here we investigate the fidelity of capture enrichment for complete mitochondrial DNA (mtDNA) genome sequencing by analyzing sequence data for nuclear copies of mtDNA (NUMTs). Using capture-enriched sequencing data from a mitochondria-free cell line and the parental cell line, and from samples previously sequenced from long-range PCR products, we demonstrate that NUMT alleles are indeed present in capture-enriched sequence data, but at low enough levels to not influence calling the authentic mtDNA genome sequence. However, distinguishing NUMT alleles from true low-level mutations (e.g. heteroplasmy) is more challenging. We develop here a computational method to distinguish NUMT alleles from heteroplasmies, using sequence data from artificial mixtures to optimize the method.
    Keywords: Genomics
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    Topics: Biology
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  • 14
    Publication Date: 2012-10-10
    Description: Single nucleotide polymorphisms (SNPs) are increasingly used to tag genetic loci associated with phenotypes such as risk of complex diseases. Technically, this is done genome-wide without prior restriction or knowledge of biological feasibility in scans referred to as genome-wide association studies (GWAS). Depending on the linkage disequilibrium (LD) structure at a particular locus, such tagSNPs may be surrogates for many thousands of other SNPs, and it is difficult to distinguish those that may play a functional role in the phenotype from those simply genetically linked. Because a large proportion of tagSNPs have been identified within non-coding regions of the genome, distinguishing functional from non-functional SNPs has been an even greater challenge. A strategy was recently proposed that prioritizes surrogate SNPs based on non-coding chromatin and epigenomic mapping techniques that have become feasible with the advent of massively parallel sequencing. Here, we introduce an R/Bioconductor software package that enables the identification of candidate functional SNPs by integrating information from tagSNP locations, lists of linked SNPs from the 1000 genomes project and locations of chromatin features which may have functional significance. Availability: FunciSNP is available from Bioconductor (bioconductor.org).
    Keywords: Genomics
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  • 15
    Publication Date: 2014-07-03
    Description: With the rise of behavioural economics has come the belief that decision-making biases justify paternalistic policies. Such views challenge the notion of consumer sovereignty and the validity of traditional approaches of economic welfare analysis. While behavioural economics might improve the effectiveness of policies that are already justified on some other market-failure grounds, this article argues that the existence of cognitive failures, alone, do not justify government regulation. If one abandons the idea that consumers know what is in their best interest, judging the merits of policies becomes arbitrary and reflects only what a paternalist wants for others. The typical behavioural economic experiment occurs with college students devoid of real-world context. The biases found in such setting may not extrapolate well to conditions where people have more experience and knowledge, and where they can learn from past mistakes. Even when behavioural biases persist in the ‘real world’, consumers face incentives to engage in activities that protect them from the adverse consequences of the biases, and public policies that shield people from such consequences reduce incentives to self-regulate. The article concludes with some ideas for future research and a discussion of the merits of freedom of choice.
    Keywords: D03 - Behavioral Economics ; Underlying Principles, I18 - Government Policy ; Regulation ; Public Health, 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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  • 16
    Publication Date: 2014-04-15
    Description: Reconstructing the evolutionary relationships of species is a major goal in biology. Despite the increasing number of completely sequenced genomes, a large number of phylogenetic projects rely on targeted sequencing and analysis of a relatively small sample of marker genes. The selection of these phylogenetic markers should ideally be based on accurate predictions of their combined, rather than individual, potential to accurately resolve the phylogeny of interest. Here we present and validate a new phylogenomics strategy to efficiently select a minimal set of stable markers able to reconstruct the underlying species phylogeny. In contrast to previous approaches, our methodology does not only rely on the ability of individual genes to reconstruct a known phylogeny, but it also explores the combined power of sets of concatenated genes to accurately infer phylogenetic relationships of species not previously analyzed. We applied our approach to two broad sets of cyanobacterial and ascomycetous fungal species, and provide two minimal sets of six and four genes, respectively, necessary to fully resolve the target phylogenies. This approach paves the way for the informed selection of phylogenetic markers in the effort of reconstructing the tree of life.
    Keywords: Genomics
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  • 17
    Publication Date: 2014-09-02
    Description: In response to low consumption levels of fruits and vegetables by Supplemental Nutrition Assistance Program (SNAP) participants, the USDA Food and Nutrition Service created the Healthy Incentives Pilot (HIP) to test the efficacy of providing a 30% incentive for purchases of targeted fruits and vegetables (TFVs). Four to six months after implementation, mean daily TFV intake for adult HIP participants was 0.22 cup-equivalents higher (24% higher) than for control-group SNAP participants. These impact estimates with a random-assignment research design generally agree with previously published nonexperimental elasticity estimates, which imply that a pure price reduction of 30% would increase fruit and vegetable consumption by about 20%.
    Keywords: I18 - Government Policy ; Regulation ; Public Health, I38 - Government Policy ; Provision and Effects of Welfare Programs
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 18
    Publication Date: 2012-10-30
    Description: The objective of this article is to gain a better understanding of firms' strategies towards nutritional tax policies and to assess their impacts from a public health point of view. We determine how new products that are nutritionally improved can successfully emerge in an asymmetrical context in which firms do not have the same strategic incentives to change the characteristics of their products. The results show that nutritional regulations may induce changes in the product quality choices by firms, but may also affect the competitive game. Under some conditions, the economic distortions are not compensated by increased health benefits.
    Keywords: H23 - Externalities ; Redistributive Effects ; Environmental Taxes and Subsidies, I18 - Government Policy ; Regulation ; Public Health, L15 - Information and Product Quality ; Standardization and Compatibility
    Print ISSN: 0165-1587
    Electronic ISSN: 1464-3618
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 19
    Publication Date: 2012-10-30
    Description: We quantify the economic and health effects of a fruit and vegetable (F&V) voucher policy designed for increasing F&V consumption among low-income consumers. The analysis combined two models: an economic model which predicts how F&V consumption is affected by a change in policy, and a health model which evaluates the impact of a change in F&V consumption in terms of death avoided and life-years saved. We find that targeted F&V voucher policies can be more cost-effective than non-targeted policies based on tax decreases, but only when the targeted policy is focused narrowly on the lowest income consumers.
    Keywords: D61 - Allocative Efficiency ; Cost-Benefit Analysis, I18 - Government Policy ; Regulation ; Public Health, 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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  • 20
    Publication Date: 2012-06-28
    Description: Environmental biosurveillance and microbial ecology studies use PCR-based assays to detect and quantify microbial taxa and gene sequences within a complex background of microorganisms. However, the fragmentary nature and growing quantity of DNA-sequence data make group-specific assay design challenging. We solved this problem by developing a software platform that enables PCR-assay design at an unprecedented scale. As a demonstration, we developed quantitative PCR assays for a globally widespread, ecologically important bacterial group in soil, Acidobacteria Group 1. A total of 33 684 Acidobacteria 16S rRNA gene sequences were used for assay design. Following 1 week of computation on a 376-core cluster, 83 assays were obtained. We validated the specificity of the top three assays, collectively predicted to detect 42% of the Acidobacteria Group 1 sequences, by PCR amplification and sequencing of DNA from soil. Based on previous analyses of 16S rRNA gene sequencing, Acidobacteria Group 1 species were expected to decrease in response to elevated atmospheric CO 2 . Quantitative PCR results, using the Acidobacteria Group 1-specific PCR assays, confirmed the expected decrease and provided higher statistical confidence than the 16S rRNA gene-sequencing data. These results demonstrate a powerful capacity to address previously intractable assay design challenges.
    Keywords: Genomics
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  • 21
    Publication Date: 2012-08-08
    Description: Due to dramatic advances in DNA technology, quantitative measures of annotation data can now be obtained in continuous coordinates across the entire genome, allowing various heterogeneous ‘genomic landscapes’ to emerge. Although much effort has been devoted to comparing DNA sequences, not much attention has been given to comparing these large quantities of data comprehensively. In this article, we introduce a method for rapidly detecting local regions that show high correlations between genomic landscapes. We overcame the size problem for genome-wide data by converting the data into series of symbols and then carrying out sequence alignment. We also decomposed the oscillation of the landscape data into different frequency bands before analysis, since the real genomic landscape is a mixture of embedded and confounded biological processes working at different scales in the cell nucleus. To verify the usefulness and generality of our method, we applied our approach to well investigated landscapes from the human genome, including several histone modifications. Furthermore, by applying our method to over 20 genomic landscapes in human and 12 in mouse, we found that DNA replication timing and the density of Alu insertions are highly correlated genome-wide in both species, even though the Alu elements have amplified independently in the two genomes. To our knowledge, this is the first method to align genomic landscapes at multiple scales according to their shape.
    Keywords: Genomics
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  • 22
    Publication Date: 2013-03-13
    Description: The numerous discovered cases of domesticated transposable element (TE) proteins led to the recognition that TEs are a significant source of evolutionary innovation. However, much less is known about the reverse process, whether and to what degree the evolution of TEs is influenced by the genome of their hosts. We addressed this issue by searching for cases of incorporation of host genes into the sequence of TEs and examined the systems-level properties of these genes using the Saccharomyces cerevisiae and Drosophila melanogaster genomes. We identified 51 cases where the evolutionary scenario was the incorporation of a host gene fragment into a TE consensus sequence, and we show that both the yeast and fly homologues of the incorporated protein sequences have central positions in the cellular networks. An analysis of selective pressure (Ka/Ks ratio) detected significant selection in 37% of the cases. Recent research on retrovirus-host interactions shows that virus proteins preferentially target hubs of the host interaction networks enabling them to take over the host cell using only a few proteins. We propose that TEs face a similar evolutionary pressure to evolve proteins with high interacting capacities and take some of the necessary protein domains directly from their hosts.
    Keywords: Genomics
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  • 23
    Publication Date: 2013-11-22
    Description: We develop a structural econometric model of the vertical contracts between soft drink manufacturers and retailers to assess the impact of taxes or changes in production costs on consumer prices. Using individual data on food purchases from a representative survey of 19,000 French households in 2005, we estimate consumer demand using a random utility approach. Among a set of possible vertical relationships, we select the model that best fits the data. We evaluate the pass-through rate of changes in input costs (sugar) or of taxes and show that the industry over-shifts cost changes or excise taxes to the consumers. This result challenges the belief that firms do not pass on the full extent of cost changes or excise taxes to consumers.
    Keywords: H32 - Firm, I18 - Government Policy ; Regulation ; Public Health, L13 - Oligopoly and Other Imperfect 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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  • 24
    Publication Date: 2014-05-28
    Description: We propose a methodology to evaluate social projects from the perspective of children's opportunities on the basis of the effects of these projects on the distribution of outcomes. We condition our evaluation on characteristics for which individuals are not responsible; in this case, we use parental education level and indigenous background. The methodology is applied to evaluate the effects on children's health opportunities of Mexico's Oportunidades program, one of the largest conditional cash transfer programs for poor households in the world. The evidence from this program shows that gains in health opportunities for children from indigenous backgrounds are substantial and are situated in crucial parts of the distribution, whereas gains for children from nonindigenous backgrounds are more limited.
    Keywords: D63 - Equity, Justice, Inequality, and Other Normative Criteria and Measurement, I18 - Government Policy ; Regulation ; Public Health, I38 - Government Policy ; Provision and Effects of Welfare Programs
    Print ISSN: 0258-6770
    Electronic ISSN: 1564-698X
    Topics: Economics
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  • 25
    Publication Date: 2012-10-24
    Description: A number of studies have shown that transcriptome analysis in terms of chromosomal location can reveal regions of non-random transcriptional activity within the genome. Genomic clusters of differentially expressed genes can identify genomic patterns of structural organization, underlying copy number variations or long-range epigenetic regulation such as X-chromosome inactivation. Here we apply an integrative bioinformatics analysis to a collection of 315 freely available mouse pluripotent stem cell samples to discover transcriptional clusters in the genome. We show that over half of the analysed samples (56.83%) carry whole or partial-chromosome spanning clusters which recur in genomic regions previously implicated in chromosomal imbalances. Strikingly, we found that the presence of such large-clusters is linked to the differential expression of a limited number of genes, common to all samples carrying clusters irrespectively of the chromosome where the cluster is found. We have used these genes to train and test classification models that can predict samples that carry large-scale clusters on any chromosome with over 90% accuracy. Our findings suggest that there is a common downstream activation in these cells that affects a limited number of nodes. We propose that this effect is linked to selective advantage and identify potential driver genes.
    Keywords: Genomics
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  • 26
    Publication Date: 2012-11-04
    Description: The rapidly growing amount of genomic sequence data being generated and made publicly available necessitate the development of new data storage and archiving methods. The vast amount of data being shared and manipulated also create new challenges for network resources. Thus, developing advanced data compression techniques is becoming an integral part of data production and analysis. The HapMap project is one of the largest public resources of human single-nucleotide polymorphisms (SNPs), characterizing over 3 million SNPs genotyped in over 1000 individuals. The standard format and biological properties of HapMap data suggest that a dedicated genetic compression method can outperform generic compression tools. We propose a compression methodology for genetic data by introducing H ap Z ipper , a lossless compression tool tailored to compress HapMap data beyond benchmarks defined by generic tools such as gzip , bzip2 and lzma . We demonstrate the usefulness of H ap Z ipper by compressing HapMap 3 populations to 〈5% of their original sizes. H ap Z ipper is freely downloadable from https://bitbucket.org/pchanda/hapzipper/downloads/HapZipper.tar.bz2 .
    Keywords: Genomics
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  • 27
    Publication Date: 2012-11-04
    Description: Spliced alignment plays a central role in the precise identification of eukaryotic gene structures. Even though many spliced alignment programs have been developed, recent rapid progress in DNA sequencing technologies demands further improvements in software tools. Benchmarking algorithms under various conditions is an indispensable task for the development of better software; however, there is a dire lack of appropriate datasets usable for benchmarking spliced alignment programs. In this study, we have constructed two types of datasets: simulated sequence datasets and actual cross-species datasets. The datasets are designed to correspond to various real situations, i.e. divergent eukaryotic species, different types of reference sequences, and the wide divergence between query and target sequences. In addition, we have developed an extended version of our program Spaln , which incorporates two additional features to the scoring scheme of the original version, and examined this extended version, Spaln2, together with the original Spaln and other representative aligners based on our benchmark datasets. Although the effects of the modifications are not individually striking, Spaln2 is consistently most accurate and reasonably fast in most practical cases, especially for plants and fungi and for increasingly divergent pairs of target and query sequences.
    Keywords: Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 28
    Publication Date: 2013-05-04
    Description: Various ‘omics’ technologies, including microarrays and gas chromatography mass spectrometry, can be used to identify hundreds of interesting genes, proteins and metabolites, such as differential genes, proteins and metabolites associated with diseases. Identifying metabolic pathways has become an invaluable aid to understanding the genes and metabolites associated with studying conditions. However, the classical methods used to identify pathways fail to accurately consider joint power of interesting gene/metabolite and the key regions impacted by them within metabolic pathways. In this study, we propose a powerful analytical method referred to as Subpathway-GM for the identification of metabolic subpathways. This provides a more accurate level of pathway analysis by integrating information from genes and metabolites, and their positions and cascade regions within the given pathway. We analyzed two colorectal cancer and one metastatic prostate cancer data sets and demonstrated that Subpathway-GM was able to identify disease-relevant subpathways whose corresponding entire pathways might be ignored using classical entire pathway identification methods. Further analysis indicated that the power of a joint genes/metabolites and subpathway strategy based on their topologies may play a key role in reliably recalling disease-relevant subpathways and finding novel subpathways.
    Keywords: Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 29
    Publication Date: 2013-04-14
    Description: Multiplex analytical systems that allow detection of multiple nucleic acid targets in one assay can provide rapid characterization of a sample while still saving cost and resources. However, few systems have proven to offer a solution for mid-plex (e.g. 10- to 50-plex) analysis that is high throughput and cost effective. Here we describe the combined use of fluorescence color and melting temperature (T m ) as a virtual 2D label that enables homogenous detection of one order of magnitude more targets than current strategies on real-time polymerase chain reaction platform. The target was first hybridized with a pair of ligation oligonucleotides, one of which harbored an artificial sequence that had a unique T m when hybridized with a reporter fluorogenic probe. The ligated products were then amplified by a universal primer pair and denatured by a melting curve analysis procedure. The targets were identified by their respective T m values in the corresponding fluorescence detection channels. The proof-of-principle of this approach was validated by genotyping 15 high-risk human papillomaviruses and 48 human single-nucleotide polymorphisms. The robustness of this method was demonstrated by analyzing a large number of clinical samples in both cases. The combined merits of multiplexity, flexibility and simplicity should make this approach suitable for a variety of applications.
    Keywords: Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 30
    Publication Date: 2012-11-25
    Description: The chromatin structure of eukaryotic telomeres plays an essential role in telomere functions. However, their study might be impaired by the presence of interstitial telomeric sequences (ITSs), which have a widespread distribution in different model systems. We have developed a simple approach to study the chromatin structure of Arabidopsis telomeres independently of ITSs by analyzing ChIP-seq data. This approach could be used to study the chromatin structure of telomeres in some other eukaryotes. The analysis of ChIP-seq experiments revealed that Arabidopsis telomeres have higher density of histone H3 than centromeres, which might reflects their short nucleosomal organization. These experiments also revealed that Arabidopsis telomeres have lower levels of heterochromatic marks than centromeres (H3K9 Me2 and H3K27 Me ), higher levels of some euchromatic marks (H3K4 Me2 and H3K9Ac) and similar or lower levels of other euchromatic marks (H3K4 Me3 , H3K36 Me2 , H3K36 Me3 and H3K18Ac). Interestingly, the ChIP-seq experiments also revealed that Arabidopsis telomeres exhibit high levels of H3K27 Me3 , a repressive mark that associates with many euchromatic genes. The epigenetic profile of Arabidopsis telomeres is closely related to the previously defined chromatin state 2. This chromatin state is found in 23% of Arabidopsis genes, many of which are repressed or lowly expressed. At least, in part, this scenario is similar in rice.
    Keywords: Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 31
    Publication Date: 2013-12-24
    Description: Policymakers have suggested the use of taxes to raise the relative cost of buying fast food. Yet, little is known of the structure of demand for food-away-from-home (FAFH) in general. This study provides estimates of the price-elasticity of demand for four different types of FAFH using a new data set from NPD, Inc. and an econometric approach that accounts for the multiple-discrete–continuous nature of FAFH demand. We find that cross-price elasticities of demand are small, so consumers are unwilling to substitute between food-at-home and any type of FAFH or among types of FAFH. Therefore, taxing fast food may be effective in reducing the number of fast food visits and shifting consumption to at-home meals.
    Keywords: C35 - Discrete Regression and Qualitative Choice Models, D12 - Consumer Economics: Empirical Analysis, I18 - Government Policy ; Regulation ; Public Health, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0165-1587
    Electronic ISSN: 1464-3618
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 32
    Publication Date: 2013-12-05
    Description: The availability of alcoholic beverages in grocery stores varies across the United States due to state-level regulations. Recently there have been a number of controversial legislative proposals to expand the distribution of certain alcoholic beverages, most notably wine. Our econometric results show that, holding constant the total quantity of alcohol consumed, a higher share of wine correlates with lower traffic fatality rates, while the opposite is true for beer. These findings suggest that arguments against the wider distribution of wine as an approach to reduce social problems may not be fully justified.
    Keywords: I18 - Government Policy ; Regulation ; Public Health, K23 - Regulated Industries and Administrative Law, 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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  • 33
    Publication Date: 2013-12-05
    Description: We study how ready or vulnerable each Primary Care Organization (PCO) in England was in 2010 to the National Health Service reforms announced in the Government white paper Equity and Excellence: Liberating the NHS, later enacted by the Health and Social Care Act 2012. We define vulnerability as a combination of latent variables and present a novel methodological approach to measuring organizational and wider impacts of health policy reforms. Areas with higher concentrations of older people were not correlated with vulnerability except where there was also deprivation. This contrasts with wide-spread qualitative and quantitative evidence of sub-optimal care of older people within the health service. This suggests there may be an over-reliance on using activity, which was proportionately higher in the least vulnerable areas, to determine funding and quality markers rather than outcomes. A risk of the reform process could be a negative impact on deprived areas which appear to be financially less secure and more likely to have long-established health inequalities.
    Keywords: C30 - General, H75 - State and Local Government: Health, Education, and Welfare, I18 - Government Policy ; Regulation ; Public Health
    Print ISSN: 2040-5790
    Electronic ISSN: 2040-5804
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 34
    Publication Date: 2014-02-14
    Description: Many policy interventions that address rising obesity levels in the United States have been designed to provide consumers with more nutrition information, with the goal of encouraging consumers to decrease their caloric intake. We discuss existing information-provision measures and suggest that they are likely to have little-to-modest impact on encouraging lower caloric intake, because making use of such information requires understanding and/or motivation, which many consumers lack, as well as self-control, which is a limited resource. We highlight several phenomena from the behavioral economics literature (present-biased preferences, visceral factors, and status quo bias) and explain how awareness of these behavioral phenomena can inform both more effective information-provision policies and additional policies for regulating restaurants and public school cafeterias that move beyond information to nudge people towards healthier food choices.
    Keywords: D00 - General, I12 - Health Production, I18 - Government Policy ; Regulation ; Public Health, L66 - Food ; Beverages ; Cosmetics ; Tobacco ; Wine and Spirits, M31 - Marketing, M38 - Government Policy and Regulation, 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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  • 35
    Publication Date: 2014-02-14
    Description: Using a lab experiment with 258 adult non-student participants, we examined whether unhealthy foods taxes, healthy foods subsidies, anti-obesity advertising, and healthy foods advertising have an impact on changing consumers' choices of lunch items and the nutrient content of their choices for a selected meal. A difference-in-difference regression model was used to determine the efficacy of the various policy treatments. The results indicate that the unhealthy foods tax, healthy foods advertising, and unhealthy foods tax combined with anti-obesity advertising significantly reduced the content of some nutrients of concern, such as calories, calories from fat, carbohydrates, and cholesterol in meal selections. We also find that when combined with healthy foods subsidy, the healthy foods advertising has very little effect on nutrient consumption; the anti-obesity advertising on its own, however, is not efficient at changing dietary behavior. We discuss the policy implications of our findings and venues for future research.
    Keywords: H20 - 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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  • 36
    Publication Date: 2014-02-14
    Description: Across health systems, there is increasing interest in applying behavioral economics insights to health policy challenges. Policy decision makers have recently discussed a range of diverse health policy interventions that are commonly brought together under a behavioral umbrella. These include randomized controlled trials, comparison portals, information labels, financial incentives, sin taxes, and nudges. A taxonomy is proposed to classify such behavioral interventions. In the context of risky health behavior, each cluster of policies is then scrutinized under two respects: (i) What are its genuinely behavioral insights? (ii) What evidence exists on its practical effectiveness? The discussion highlights the main challenges in drawing a clear mapping between how much each policy is behaviorally inspired and its effectiveness.
    Keywords: C90 - General, D03 - Behavioral Economics ; Underlying Principles, I10 - General, I18 - Government Policy ; Regulation ; Public Health
    Print ISSN: 2040-5790
    Electronic ISSN: 2040-5804
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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