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  • Computational Methods  (4)
  • Regulation  (4)
  • Oxford University Press  (8)
  • Hindawi
  • International Union of Crystallography (IUC)
  • 2010-2014  (8)
  • 2013  (8)
  • 1
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    TrAp: a tree approach for fingerprinting subclonal tumor composition (2013)
    Oxford University Press
    Details
    Publication Date: 2013-09-26
    Description: Revealing the clonal composition of a single tumor is essential for identifying cell subpopulations with metastatic potential in primary tumors or with resistance to therapies in metastatic tumors. Sequencing technologies provide only an overview of the aggregate of numerous cells. Computational approaches to de-mix a collective signal composed of the aberrations of a mixed cell population of a tumor sample into its individual components are not available. We propose an evolutionary framework for deconvolving data from a single genome-wide experiment to infer the composition, abundance and evolutionary paths of the underlying cell subpopulations of a tumor. We have developed an algorithm (TrAp) for solving this mixture problem. In silico analyses show that TrAp correctly deconvolves mixed subpopulations when the number of subpopulations and the measurement errors are moderate. We demonstrate the applicability of the method using tumor karyotypes and somatic hypermutation data sets. We applied TrAp to Exome-Seq experiment of a renal cell carcinoma tumor sample and compared the mutational profile of the inferred subpopulations to the mutational profiles of single cells of the same tumor. Finally, we deconvolve sequencing data from eight acute myeloid leukemia patients and three distinct metastases of one melanoma patient to exhibit the evolutionary relationships of their subpopulations.
    Keywords: Computational Methods
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Global profiling of miRNAs and the hairpin precursors: insights into miRNA processing and novel miRNA discovery (2013)
    Oxford University Press
    Details
    Publication Date: 2013-04-02
    Description: MicroRNAs (miRNAs) constitute an important class of small regulatory RNAs that are derived from distinct hairpin precursors (pre-miRNAs). In contrast to mature miRNAs, which have been characterized in numerous genome-wide studies of different organisms, research on global profiling of pre-miRNAs is limited. Here, using massive parallel sequencing, we have performed global characterization of both mouse mature and precursor miRNAs. In total, 87 369 704 and 252 003 sequencing reads derived from 887 mature and 281 precursor miRNAs were obtained, respectively. Our analysis revealed new aspects of miRNA/pre-miRNA processing and modification, including eight Ago2-cleaved pre-miRNAs, eight new instances of miRNA editing and exclusively 5' tailed mirtrons. Furthermore, based on the sequences of both mature and precursor miRNAs, we developed a miRNA discovery pipeline, miRGrep, which does not rely on the availability of genome reference sequences. In addition to 239 known mouse pre-miRNAs, miRGrep predicted 41 novel ones with high confidence. Similar as known ones, the mature miRNAs derived from most of these novel loci showed both reduced abundance following Dicer knockdown and the binding with Argonaute2. Evaluation on data sets obtained from Caenorhabditis elegans and Caenorhabditis sp.11 demonstrated that miRGrep could be widely used for miRNA discovery in metazoans, especially in those without genome reference sequences.
    Keywords: Computational Methods
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 3
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    Utilizing sequence intrinsic composition to classify protein-coding and long non-coding transcripts (2013)
    Oxford University Press
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    Publication Date: 2013-09-26
    Description: It is a challenge to classify protein-coding or non-coding transcripts, especially those re-constructed from high-throughput sequencing data of poorly annotated species. This study developed and evaluated a powerful signature tool, Coding-Non-Coding Index (CNCI), by profiling adjoining nucleotide triplets to effectively distinguish protein-coding and non-coding sequences independent of known annotations. CNCI is effective for classifying incomplete transcripts and sense–antisense pairs. The implementation of CNCI offered highly accurate classification of transcripts assembled from whole-transcriptome sequencing data in a cross-species manner, that demonstrated gene evolutionary divergence between vertebrates, and invertebrates, or between plants, and provided a long non-coding RNA catalog of orangutan. CNCI software is available at http://www.bioinfo.org/software/cnci .
    Keywords: Computational Methods
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 4
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    r3Cseq: an R/Bioconductor package for the discovery of long-range genomic interactions from chromosome conformation capture and next-generation sequencing data (2013)
    Oxford University Press
    Details
    Publication Date: 2013-07-16
    Description: The coupling of chromosome conformation capture (3C) with next-generation sequencing technologies enables the high-throughput detection of long-range genomic interactions, via the generation of ligation products between DNA sequences, which are closely juxtaposed in vivo . These interactions involve promoter regions, enhancers and other regulatory and structural elements of chromosomes and can reveal key details of the regulation of gene expression. 3C-seq is a variant of the method for the detection of interactions between one chosen genomic element (viewpoint) and the rest of the genome. We present r3Cseq , an R/Bioconductor package designed to perform 3C-seq data analysis in a number of different experimental designs. The package reads a common aligned read input format, provides data normalization, allows the visualization of candidate interaction regions and detects statistically significant chromatin interactions, thus greatly facilitating hypothesis generation and the interpretation of experimental results. We further demonstrate its use on a series of real-world applications.
    Keywords: Computational Methods
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 5
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    Impact of Cost Shocks on Consumer Prices in Vertically-Related Markets: The Case of The French Soft Drink Market (2013)
    Oxford University Press
    Details
    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
    Published by Oxford University Press
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  • 6
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    Demand for food-away-from-home: a multiple-discrete-continuous extreme value model (2013)
    Oxford University Press
    Details
    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
    Published by Oxford University Press
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  • 7
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    Economic and Social Implications of Regulating Alcohol Availability in Grocery Stores (2013)
    Oxford University Press
    Details
    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
    Published by Oxford University Press
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  • 8
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    Vulnerability of Primary Care Organizations to the National Health Service Reform in England (2013)
    Oxford University Press
    Details
    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
    Published by Oxford University Press
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