Author
Soma Das
Other affiliations: University of Illinois at Chicago, NorthShore University HealthSystem, University of Texas MD Anderson Cancer Center ...read more
Bio: Soma Das is an academic researcher from University of Chicago. The author has contributed to research in topics: Exome sequencing & Germline mutation. The author has an hindex of 55, co-authored 160 publications receiving 22523 citations. Previous affiliations of Soma Das include University of Illinois at Chicago & NorthShore University HealthSystem.
Topics: Exome sequencing, Germline mutation, Population, Cancer, Gene
Papers published on a yearly basis
Papers
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TL;DR: Because of the increased complexity of analysis and interpretation of clinical genetic testing described in this report, the ACMG strongly recommends thatclinical molecular genetic testing should be performed in a Clinical Laboratory Improvement Amendments–approved laboratory, with results interpreted by a board-certified clinical molecular geneticist or molecular genetic pathologist or the equivalent.
17,834 citations
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TL;DR: UGT1A1 genotype and total bilirubin levels are strongly associated with severe neutropenia, and could be used to identify cancer patients predisposed to the severe toxicity of irinotecan.
Abstract: Purpose Severe toxicity is commonly observed in cancer patients receiving irinotecan. UDP-glucuronosyltransferase 1A1 (UGT1A1) catalyzes the glucuronidation of the active metabolite SN-38. This study prospectively evaluated the association between the prevalence of severe toxicity and UGT1A1 genetic variation. Patients and Methods Sixty-six cancer patients with advanced disease refractory to other treatments received irinotecan 350 mg/m2 every 3 weeks. Toxicity and pharmacokinetic data were measured during cycle 1. UGT1A1 variants (−3279G>T, −3156G>A, promoter TA indel, 211G>A, 686C>A) were genotyped. Results The prevalence of grade 4 neutropenia was 9.5%. Grade 4 neutropenia was much more common in patients with the TA indel 7/7 genotype (3 of 6 patients; 50%) compared with 6/7 (3 of 24 patients; 12.5%) and 6/6 (0 of 29 patients; 0%) (P = .001). The TA indel genotype was significantly associated with the absolute neutrophil count nadir (7/7 < 6/7 < 6/6, P = .02). The relative risk of grade 4 neutropenia ...
933 citations
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TL;DR: The ACMG strongly recommends that the clinical and technical validation of sequence variation detection be performed in a CLIA-approved laboratory and interpreted by a board-certified clinical molecular geneticist or equivalent.
730 citations
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TL;DR: It is suggested that screening for UGT1A1*28 polymorphism may identify patients with lower SN-38 glucuronidation rates and greater susceptibility to irinotecan induced gastrointestinal and bone marrow toxicity.
Abstract: The metabolism of irinotecan (CPT-11) involves sequential activation to SN-38 and detoxification to the pharmacologically inactive SN-38 glucuronide (SN-38G). We have previously demonstrated the role of UGT1A1 enzyme in the glucuronidation of SN-38 and a significant correlation between in vitro glucuronidation of SN-38 and UGT1A1 gene promoter polymorphism. This polymorphism (UGT1A1*28) is characterized by the presence of an additional TA repeat in the TATA sequence of the UGT1A1 promoter, ((TA)7TAA, instead of (TA)6TAA). Here we report the results from a prospective clinical pharmacogenetic study to determine the significance of UGT1A1*28 polymorphism on irinotecan disposition and toxicity in patients with cancer. Twenty patients with solid tumors were treated with a 90 min i.v. infusion of irinotecan (300 mg m(-2)) once every 3 weeks. The frequency of UGT1A1 genotypes was as follows: 6/6--45%, 6/7--35% and 7/7--20%, with allele frequencies of 0.375 and 0.625 for (TA)7TAA and (TA)6TAA, respectively. Patients with the (TA)7TAA polymorphism had significantly lower SN-38 glucuronidation rates than those with the normal allele (6/6>6/7>7/7, P = 0.001). More severe grades of diarrhea and neutropenia were observed only in patients heterozygous (grade 4 diarrhea, n = 1) or homozygous (grade 3 diarrhea/grade 4 neutropenia, n = 1 and grade 3 neutropenia, n = 1) for the (TA)7TAA sequence. The results suggest that screening for UGT1A1*28 polymorphism may identify patients with lower SN-38 glucuronidation rates and greater susceptibility to irinotecan induced gastrointestinal and bone marrow toxicity.
682 citations
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Centers for Disease Control and Prevention1, Medical College of Wisconsin2, Illumina3, University of Utah4, National Institutes of Health5, United States Department of Health and Human Services6, Emory University7, GeneDx8, University of Chicago9, Mayo Clinic10, Harvard University11, Life Technologies12, Pacific Biosciences13, Washington University in St. Louis14, Celera Corporation15, Stanford University16, Hoffmann-La Roche17, National Institute of Standards and Technology18
TL;DR: This research highlights the need to understand more fully the role of Epstein-Barr virus in infectious disease and its role in Hunter-LaSalle syndrome.
Abstract: Amy S Gargis, Centers for Disease Control and Prevention Lisa Kalman, Centers for Disease Control and Prevention Meredith W Berry, SeqWright Inc David P Bick, Medical College of Wisconsin David P Dimmock, Medical College of Wisconsin Tina Hambuch, Illumina Clinical Services Fei Lu, SeqWright Inc Elaine Lyon, University of Utah Karl V Voelkerding, University of Utah Barbara Zehnbauer, Emory University
435 citations
Cited by
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TL;DR: Because of the increased complexity of analysis and interpretation of clinical genetic testing described in this report, the ACMG strongly recommends thatclinical molecular genetic testing should be performed in a Clinical Laboratory Improvement Amendments–approved laboratory, with results interpreted by a board-certified clinical molecular geneticist or molecular genetic pathologist or the equivalent.
17,834 citations
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Harvard University1, Broad Institute2, Boston Children's Hospital3, University of Washington4, University of Arizona5, Cardiff University6, Google7, Icahn School of Medicine at Mount Sinai8, Samsung Medical Center9, Vertex Pharmaceuticals10, University of Michigan11, University of Cambridge12, State University of New York Upstate Medical University13, Karolinska Institutet14, University of Eastern Finland15, Wellcome Trust Centre for Human Genetics16, University of Oxford17, Cedars-Sinai Medical Center18, University of Ottawa19, University of Pennsylvania20, University of North Carolina at Chapel Hill21, University of Helsinki22, University of California, San Diego23, University of Mississippi Medical Center24
TL;DR: The aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC) provides direct evidence for the presence of widespread mutational recurrence.
Abstract: Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of predicted protein-truncating variants, with 72% of these genes having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human 'knockout' variants in protein-coding genes.
8,758 citations
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TL;DR: Small-molecule therapeutics that block PI3K signalling might deal a severe blow to cancer cells by blocking many aspects of the tumour-cell phenotype.
Abstract: One signal that is overactivated in a wide range of tumour types is the production of a phospholipid, phosphatidylinositol (3,4,5) trisphosphate, by phosphatidylinositol 3-kinase (PI3K) This lipid and the protein kinase that is activated by it — AKT — trigger a cascade of responses, from cell growth and proliferation to survival and motility, that drive tumour progression Small-molecule therapeutics that block PI3K signalling might deal a severe blow to cancer cells by blocking many aspects of the tumour-cell phenotype
5,654 citations
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TL;DR: The UniProtKB responded to the COVID-19 pandemic through expert curation of relevant entries that were rapidly made available to the research community through a dedicated portal and a credit-based publication submission interface was developed.
Abstract: Abstract The aim of the UniProt Knowledgebase is to provide users with a comprehensive, high-quality and freely accessible set of protein sequences annotated with functional information. In this article, we describe significant updates that we have made over the last two years to the resource. The number of sequences in UniProtKB has risen to approximately 190 million, despite continued work to reduce sequence redundancy at the proteome level. We have adopted new methods of assessing proteome completeness and quality. We continue to extract detailed annotations from the literature to add to reviewed entries and supplement these in unreviewed entries with annotations provided by automated systems such as the newly implemented Association-Rule-Based Annotator (ARBA). We have developed a credit-based publication submission interface to allow the community to contribute publications and annotations to UniProt entries. We describe how UniProtKB responded to the COVID-19 pandemic through expert curation of relevant entries that were rapidly made available to the research community through a dedicated portal. UniProt resources are available under a CC-BY (4.0) license via the web at https://www.uniprot.org/.
4,001 citations
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TL;DR: It is concluded that multiple Imputation for Nonresponse in Surveys should be considered as a legitimate method for answering the question of why people do not respond to survey questions.
Abstract: 25. Multiple Imputation for Nonresponse in Surveys. By D. B. Rubin. ISBN 0 471 08705 X. Wiley, Chichester, 1987. 258 pp. £30.25.
3,216 citations