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  • 1
    Publication Date: 2012-11-11
    Description: Motivation : The invention of next-generation sequencing technology has made it possible to study the rare variants that are more likely to pinpoint causal disease genes. To make such experiments financially viable, DNA samples from several subjects are often pooled before sequencing. This induces large between-pool variation which, together with other sources of experimental error, creates over-dispersed data. Statistical analysis of pooled sequencing data needs to appropriately model this additional variance to avoid inflating the false-positive rate. Results : We propose a new statistical method based on an extra-binomial model to address the over-dispersion and apply it to pooled case-control data. We demonstrate that our model provides a better fit to the data than either a standard binomial model or a traditional extra-binomial model proposed by Williams and can analyse both rare and common variants with lower or more variable pool depths compared to the other methods. Availability : Package ‘extraBinomial’ is on http://cran.r-project.org/ Contact : chris.wallace@cimr.cam.ac.uk Supplementary information: Supplementary data are available at Bioinformatics Online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 2
    Publication Date: 2014-05-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clayton, Janine A -- Collins, Francis S -- England -- Nature. 2014 May 15;509(7500):282-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24834516" target="_blank"〉PubMed〈/a〉
    Keywords: *Animal Experimentation/standards ; Animals ; Animals, Laboratory ; Biomedical Research/economics/*methods/standards ; Cell Line ; Disease Models, Animal ; Encephalomyelitis, Autoimmune, Experimental/pathology ; Female ; Financing, Organized/organization & administration ; Humans ; Male ; Multiple Sclerosis/drug therapy/pathology ; *National Institutes of Health (U.S.)/economics ; Neurons/cytology/drug effects/pathology ; Peer Review, Research/standards ; *Research Design/standards ; *Sex Characteristics ; *Sex Ratio ; Substance-Related Disorders/drug therapy/physiopathology ; United States
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2016-03-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Collins, Francis S -- Anderson, James M -- Austin, Christopher P -- Battey, James F -- Birnbaum, Linda S -- Briggs, Josephine P -- Clayton, Janine A -- Cuthbert, Bruce -- Eisinger, Robert W -- Fauci, Anthony S -- Gallin, John I -- Gibbons, Gary H -- Glass, Roger I -- Gottesman, Michael M -- Gray, Patricia A -- Green, Eric D -- Greider, Franziska B -- Hodes, Richard -- Hudson, Kathy L -- Humphreys, Betsy -- Katz, Stephen I -- Koob, George F -- Koroshetz, Walter J -- Lauer, Michael S -- Lorsch, Jon R -- Lowy, Douglas R -- McGowan, John J -- Murray, David M -- Nakamura, Richard -- Norris, Andrea -- Perez-Stable, Eliseo J -- Pettigrew, Roderic I -- Riley, William T -- Rodgers, Griffin P -- Sieving, Paul A -- Somerman, Martha J -- Spong, Catherine Y -- Tabak, Lawrence A -- Volkow, Nora D -- Wilder, Elizabeth L -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1405. doi: 10.1126/science.351.6280.1405-a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Office of the Director, NIH, Bethesda, MD 20892, USA. collinsf@mail.nih.gov. ; Division of Program Coordination, Planning, and Strategic Initiatives, NIH, Bethesda, MD 20892, USA. ; National Center for Advancing Translational Science, NIH, Rockville, MD 20850, USA. ; National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA. ; National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA. ; National Center for Complementary and Integrative Health, NIH, Bethesda, MD 20892, USA. ; Office of Research on Women's Health, NIH, Bethesda, MD 20892, USA. ; National Institute of Mental Health, NIH, Bethesda, MD 20892, USA. ; Office of AIDS Research, NIH, Bethesda, MD 20892, USA. ; National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA. ; Clinical Center, NIH, Bethesda, MD 20892, USA. ; National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA. ; Fogarty International Center, NIH, Bethesda, MD 20892, USA. ; Office of Intramural Research, NIH, Bethesda, MD 20892, USA. ; National Institute of Nursing Research, NIH, Bethesda, MD 20892, USA. ; National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA. ; Office of Research Infrastructure Programs, NIH, Bethesda, MD 20892, USA. ; National Institute on Aging, NIH, Bethesda, MD 20892, USA. ; Office of the Director, NIH, Bethesda, MD 20892, USA. ; National Library of Medicine, NIH, Bethesda, MD 20892, USA. ; National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892, USA. ; National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892, USA. ; NINDS, NIH, Bethesda, MD 20892, USA. ; Office of Extramural Research, NIH, Bethesda, MD 20892, USA. ; National Institute of General Medical Sciences, NIH, Bethesda, MD 20892, USA. ; National Cancer Institute, NIH, Bethesda, MD 20892, USA. ; Office of Management, NIH, Bethesda, MD 20892, USA. ; Office of Disease Prevention, NIH, Bethesda, MD 20892, USA. ; Center for Scientific Review, NIH, Bethesda, MD 20892, USA. ; Center for Information Technology, NIH, Bethesda, MD 20892, USA. ; National Institute on Minority Health and Health Disparities, NIH, Bethesda, MD 20892, USA. ; National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, MD 20892, USA. ; Office of Behavioral and Social Sciences Research, NIH, Bethesda, MD 20892, USA. ; National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA. ; National Eye Institute, NIH, Bethesda, MD 20892, USA. ; National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892, USA. ; Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA. ; National Institute on Drug Abuse, NIH, Bethesda, MD 20892, USA. ; Office of Strategic Coordination, NIH, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013720" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomedical Research/*economics ; Humans ; National Institutes of Health (U.S.)/*economics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2012-05-25
    Description: One mechanism by which disease-associated DNA variation can alter disease risk is altering gene expression. However, linkage disequilibrium (LD) between variants, mostly single-nucleotide polymorphisms (SNPs), means it is not sufficient to show that a particular variant associates with both disease and expression, as there could be two distinct causal variants in LD. Here, we describe a formal statistical test of colocalization and apply it to type 1 diabetes (T1D)-associated regions identified mostly through genome-wide association studies and expression quantitative trait loci (eQTLs) discovered in a recently determined large monocyte expression data set from the Gutenberg Health Study (1370 individuals), with confirmation sought in an additional data set from the Cardiogenics Transcriptome Study (558 individuals). We excluded 39 out of 60 overlapping eQTLs in 49 T1D regions from possible colocalization and identified 21 coincident eQTLs, representing 21 genes in 14 distinct T1D regions. Our results reflect the importance of monocyte (and their derivatives, macrophage and dendritic cell) gene expression in human T1D and support the candidacy of several genes as causal factors in autoimmune pancreatic beta-cell destruction, including AFF3, CD226, CLECL1, DEXI, FKRP, PRKD2, RNLS, SMARCE1 and SUOX , in addition to the recently described GPR183 (EBI2) gene.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 5
    Publication Date: 2019
    Description: Abstract Gas hydrates can form more or less at the same time as seafloor sediment. They can have the effect of significantly stiffening and strengthening deep‐ocean sediments. Subsequent increases in situ temperature or decreases in pressure may trigger hydrate dissociation, leading to large reductions in the strength and stiffness of the sediment and possible seafloor instability. Gas hydrate dissociation not only removes cementing. It also releases freshwater and significant amounts of trapped gas that are dependent on multiple factors such as type of sediment, available pore space, hydrate morphology, and hydrate saturation. The presence of pock marks in areas of known seabed instability suggests that hydrate dissociation may have been a factor in triggering failure at these locations. Having reviewed the mechanisms by which the strength and stiffness of seabed sediment may be changed during dissociation, this paper reports the results of laboratory testing to evaluate the effects of loss of hydrate cement on strength and stiffness, for a range of sand‐sized materials with differing particle size, specific surface area, and particle shape, using a laboratory gas hydrate triaxial apparatus. The results suggest that both the strength and the stiffness of hydrate‐cemented granular materials are affected significantly by the specific surface available for hydrate cementation and, to a certain extent, by the particle shape. Uniform coarse granular sediments of lower specific surface area can suffer significant loss of stiffness and strength upon hydrate dissociation, changing the sediment from dilative to contractive. Finer‐grained sediments appear less affected by dissociation.
    Print ISSN: 2169-9313
    Electronic ISSN: 2169-9356
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 6
    Publication Date: 1990-03-01
    Print ISSN: 1025-9112
    Electronic ISSN: 1616-1068
    Topics: Geosciences
    Published by Springer
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  • 7
    Publication Date: 1991-01-01
    Print ISSN: 0149-1423
    Electronic ISSN: 1943-2674
    Topics: Geosciences
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