Institution
Children's Hospital of Philadelphia
Healthcare•Philadelphia, Pennsylvania, United States•
About: Children's Hospital of Philadelphia is a healthcare organization based out in Philadelphia, Pennsylvania, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 15938 authors who have published 31815 publications receiving 1138929 citations. The organization is also known as: CHOP.
Topics: Population, Medicine, Poison control, Transplantation, Health care
Papers published on a yearly basis
Papers
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TL;DR: The ANNOVAR tool to annotate single nucleotide variants and insertions/deletions, such as examining their functional consequence on genes, inferring cytogenetic bands, reporting functional importance scores, finding variants in conserved regions, or identifying variants reported in the 1000 Genomes Project and dbSNP is developed.
Abstract: High-throughput sequencing platforms are generating massive amounts of genetic variation data for diverse genomes, but it remains a challenge to pinpoint a small subset of functionally important variants. To fill these unmet needs, we developed the ANNOVAR tool to annotate single nucleotide variants (SNVs) and insertions/deletions, such as examining their functional consequence on genes, inferring cytogenetic bands, reporting functional importance scores, finding variants in conserved regions, or identifying variants reported in the 1000 Genomes Project and dbSNP. ANNOVAR can utilize annotation databases from the UCSC Genome Browser or any annotation data set conforming to Generic Feature Format version 3 (GFF3). We also illustrate a 'variants reduction' protocol on 4.7 million SNVs and indels from a human genome, including two causal mutations for Miller syndrome, a rare recessive disease. Through a stepwise procedure, we excluded variants that are unlikely to be causal, and identified 20 candidate genes including the causal gene. Using a desktop computer, ANNOVAR requires ∼4 min to perform gene-based annotation and ∼15 min to perform variants reduction on 4.7 million variants, making it practical to handle hundreds of human genomes in a day. ANNOVAR is freely available at http://www.openbioinformatics.org/annovar/.
10,461 citations
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Mohammad H. Forouzanfar1, Lily Alexander, H. Ross Anderson, Victoria F Bachman1 +733 more•Institutions (289)
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as discussed by the authors provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.
5,668 citations
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TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) as discussed by the authors was used to estimate the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.
5,050 citations
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TL;DR: The Global Burden of Disease 2015 Study provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015, finding several countries in sub-Saharan Africa had very large gains in life expectancy, rebounding from an era of exceedingly high loss of life due to HIV/AIDS.
4,804 citations
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TL;DR: A fundamental problem with cancer genome studies is described: as the sample size increases, the list of putatively significant genes produced by current analytical methods burgeons into the hundreds and the list includes many implausible genes, suggesting extensive false-positive findings that overshadow true driver events.
Abstract: Major international projects are underway that are aimed at creating a comprehensive catalogue of all the genes responsible for the initiation and progression of cancer. These studies involve the sequencing of matched tumour-normal samples followed by mathematical analysis to identify those genes in which mutations occur more frequently than expected by random chance. Here we describe a fundamental problem with cancer genome studies: as the sample size increases, the list of putatively significant genes produced by current analytical methods burgeons into the hundreds. The list includes many implausible genes (such as those encoding olfactory receptors and the muscle protein titin), suggesting extensive false-positive findings that overshadow true driver events. We show that this problem stems largely from mutational heterogeneity and provide a novel analytical methodology, MutSigCV, for resolving the problem. We apply MutSigCV to exome sequences from 3,083 tumour-normal pairs and discover extraordinary variation in mutation frequency and spectrum within cancer types, which sheds light on mutational processes and disease aetiology, and in mutation frequency across the genome, which is strongly correlated with DNA replication timing and also with transcriptional activity. By incorporating mutational heterogeneity into the analyses, MutSigCV is able to eliminate most of the apparent artefactual findings and enable the identification of genes truly associated with cancer.
4,411 citations
Authors
Showing all 16215 results
Name | H-index | Papers | Citations |
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John Q. Trojanowski | 226 | 1467 | 213948 |
Carlo M. Croce | 198 | 1135 | 189007 |
Virginia M.-Y. Lee | 194 | 993 | 148820 |
Julie E. Buring | 186 | 950 | 132967 |
David H. Weinberg | 183 | 700 | 171424 |
Paul M. Thompson | 183 | 2271 | 146736 |
David W. Bates | 159 | 1239 | 116698 |
Leroy Hood | 158 | 853 | 128452 |
Carl H. June | 156 | 835 | 98904 |
Daniel J. Rader | 155 | 1026 | 107408 |
Hakon Hakonarson | 152 | 968 | 101604 |
James M. Wilson | 150 | 1010 | 78686 |
Kevin Murphy | 146 | 728 | 120475 |
Richard O. Hynes | 143 | 442 | 97442 |
Giorgio Trinchieri | 138 | 433 | 78028 |