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  • Computational Methods, Massively Parallel (Deep) Sequencing, Genomics  (4)
  • Bioeconomics  (3)
  • Oxford University Press  (7)
  • Copernicus
  • 1
    Publication Date: 2014-04-03
    Description: Recent advances in high-throughput sequencing (HTS) technologies and computing capacity have produced unprecedented amounts of genomic data that have unraveled the genetics of phenotypic variability in several species. However, operating and integrating current software tools for data analysis still require important investments in highly skilled personnel. Developing accurate, efficient and user-friendly software packages for HTS data analysis will lead to a more rapid discovery of genomic elements relevant to medical, agricultural and industrial applications. We therefore developed Next-Generation Sequencing Eclipse Plug-in (NGSEP), a new software tool for integrated, efficient and user-friendly detection of single nucleotide variants (SNVs), indels and copy number variants (CNVs). NGSEP includes modules for read alignment, sorting, merging, functional annotation of variants, filtering and quality statistics. Analysis of sequencing experiments in yeast, rice and human samples shows that NGSEP has superior accuracy and efficiency, compared with currently available packages for variants detection. We also show that only a comprehensive and accurate identification of repeat regions and CNVs allows researchers to properly separate SNVs from differences between copies of repeat elements. We expect that NGSEP will become a strong support tool to empower the analysis of sequencing data in a wide range of research projects on different species.
    Keywords: Computational Methods, Massively Parallel (Deep) Sequencing, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 2
    Publication Date: 2016-03-31
    Description: Conserving contiguous areas often enhances environmental benefits. However, most conservation efforts are incentive-based and voluntary, and neither reward landowners for contiguity nor do they select based on contiguity. Thus, achieving optimal contiguity of conserved parcels is unlikely. Using lab and artefactual field experiments, this paper evaluates two mechanisms in the context of reverse auctions for achieving optimal contiguity: network bonuses and spatial targeting. Results suggest that spatial targeting alone improves the aggregate environmental and social welfare outcomes, while network bonuses alone result in worse outcomes. The interaction of the bonus effect and the targeting effect is positive. If a program was already using a competitive auction environment with bonuses, adding spatial targeting could reduce welfare loss.
    Keywords: C90 - General, Q20 - General, Q57 - Ecological Economics: Ecosystem Services ; Biodiversity Conservation ; Bioeconomics
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 3
    Publication Date: 2015-03-01
    Description: The progression and clonal development of tumors often involve amplifications and deletions of genomic DNA. Estimation of allele-specific copy number, which quantifies the number of copies of each allele at each variant loci rather than the total number of chromosome copies, is an important step in the characterization of tumor genomes and the inference of their clonal history. We describe a new method, falcon , for f inding somatic al lele-specific co py n umber changes by next generation sequencing of tumors with matched normals. falcon is based on a change-point model on a bivariate mixed Binomial process, which explicitly models the copy numbers of the two chromosome haplotypes and corrects for local allele-specific coverage biases. By using the Binomial distribution rather than a normal approximation, falcon more effectively pools evidence from sites with low coverage. A modified Bayesian information criterion is used to guide model selection for determining the number of copy number events. Falcon is evaluated on in silico spike-in data and applied to the analysis of a pre-malignant colon tumor sample and late-stage colorectal adenocarcinoma from the same individual. The allele-specific copy number estimates obtained by falcon allows us to draw detailed conclusions regarding the clonal history of the individual's colon cancer.
    Keywords: Computational Methods, Massively Parallel (Deep) Sequencing, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 4
    Publication Date: 2012-05-13
    Description: The informational content of RNA sequencing is currently far from being completely explored. Most of the analyses focus on processing tables of counts or finding isoform deconvolution via exon junctions. This article presents a comparison of several techniques that can be used to estimate differential expression of exons or small genomic regions of expression, based on their coverage function shapes. The problem is defined as finding the differentially expressed exons between two samples using local expression profile normalization and statistical measures to spot the differences between two profile shapes. Initial experiments have been done using synthetic data, and real data modified with synthetically created differential patterns. Then, 160 pipelines (5 types of generator x 4 normalizations x 8 difference measures) are compared. As a result, the best analysis pipelines are selected based on linearity of the differential expression estimation and the area under the ROC curve. These platform-independent techniques have been implemented in the Bioconductor package rnaSeqMap. They point out the exons with differential expression or internal splicing, even if the counts of reads may not show this. The areas of application include significant difference searches, splicing identification algorithms and finding suitable regions for QPCR primers.
    Keywords: Computational Methods, Massively Parallel (Deep) Sequencing, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 5
    Publication Date: 2014-03-13
    Description: Genetic disorders can be detected by prenatal diagnosis using Chorionic Villus Sampling, but the 1:100 chance to result in miscarriage restricts the use to fetuses that are suspected to have an aberration. Detection of trisomy 21 cases noninvasively is now possible owing to the upswing of next-generation sequencing (NGS) because a small percentage of fetal DNA is present in maternal plasma. However, detecting other trisomies and smaller aberrations can only be realized using high-coverage NGS, making it too expensive for routine practice. We present a method, WISECONDOR (WIthin-SamplE COpy Number aberration DetectOR), which detects small aberrations using low-coverage NGS. The increased detection resolution was achieved by comparing read counts within the tested sample of each genomic region with regions on other chromosomes that behave similarly in control samples. This within-sample comparison avoids the need to re-sequence control samples. WISECONDOR correctly identified all T13, T18 and T21 cases while coverages were as low as 0.15–1.66. No false positives were identified. Moreover, WISECONDOR also identified smaller aberrations, down to 20 Mb, such as del(13)(q12.3q14.3), +i(12)(p10) and i(18)(q10). This shows that prevalent fetal copy number aberrations can be detected accurately and affordably by shallow sequencing maternal plasma. WISECONDOR is available at bioinformatics.tudelft.nl/wisecondor.
    Keywords: Computational Methods, Massively Parallel (Deep) Sequencing, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 6
    Publication Date: 2014-07-03
    Description: In this paper, we discuss the importance of developing integrated assessment models to support the design and implementation of policies to address water quality problems associated with agricultural pollution. We describe a new modelling system, LUMINATE, which links land use decisions made at the field scale in the Upper Mississippi, Ohio and Tennessee Basins through both environmental and hydrological components to downstream water quality effects and hypoxia in the Gulf of Mexico. This modelling system can be used to analyse detailed policy scenarios identifying the costs of the policies and their resulting benefits for improved local and regional water quality. We demonstrate the model's capabilities with a simple scenario where cover crops are incentivised with green payments over a large expanse of the watershed.
    Keywords: Q51 - Valuation of Environmental Effects, Q52 - Pollution Control Costs ; Distributional Effects ; Employment Effects, Q57 - Ecological Economics: Ecosystem Services ; Biodiversity Conservation ; Bioeconomics
    Print ISSN: 0165-1587
    Electronic ISSN: 1464-3618
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 7
    Publication Date: 2017-01-05
    Description: Resource managers must often make difficult choices in the face of imperfectly observed and dynamically changing systems (e.g., livestock, fisheries, water, and invasive species). A rich set of techniques exists for identifying optimal choices when that uncertainty is assumed to be understood and irreducible. Standard optimization approaches, however, cannot address situations in which reducible uncertainty applies to either system behavior or environmental states. The adaptive management literature overcomes this limitation with tools for optimal learning, but has been limited to highly simplified models with state and action spaces that are discrete and small. We overcome this problem by using a recently developed extension of the Partially Observable Markov Decision Process (POMDP) framework to allow for learning about a continuous state. We illustrate this methodology by exploring optimal control of bovine tuberculosis in New Zealand cattle. Disease testing—the control variable—serves to identify herds for treatment and provides information on prevalence, which is both imperfectly observed and subject to change due to controllable and uncontrollable factors. We find substantial efficiency losses from both ignoring learning (standard stochastic optimization) and from simplifying system dynamics (to facilitate a typical, simple learning model), though the latter effect dominates in our setting. We also find that under an adaptive management approach, simplifying dynamics can lead to a belief trap in which information gathering ceases, beliefs become increasingly inaccurate, and losses abound.
    Keywords: C61 - Optimization Techniques ; Programming Models ; Dynamic Analysis, H41 - Public Goods, Q18 - Agricultural Policy ; Food Policy, Q57 - Ecological Economics: Ecosystem Services ; Biodiversity Conservation ; Bioeconomics
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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