Shamil R. Sunyaev, Ph.D.
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Associate Geneticist, Brigham and Women's Hospital
Professor of Biomedical Informatics, Harvard Medical School
Brigham and Women's Hospital Department of Medicine Genetics 75 Francis Street Boston, MA 02115
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Research Narrative:
We are a computational biology laboratory. We develop and apply computational methods to pursue various problems in fields of genetics, genomics and proteomics. We develop novel computational techniques for proteomics and for comparative analysis of protein sequences and structures.
Our main interest is to analyze genetic variation and genome divergence between species with focus on protein coding regions. By predicting the effects of amino acid substitutions on protein structure and function and by using large scale statistical and computational approaches, we can learn more about the evolutionary process of natural selection and the evolution of proteins. We use a translational approach in that we use our methods to investigate the contribution of human genetic polymorphisms to complex disease traits, for example we have been investigating the genetic contribution to high density lipoprotein (HDL) levels in humans.
Other efforts are directed towards developing methods to best use available population genetic variation data to investigate potential mechanisms of function and evolution. For example, we are investigating potential epistatic interactions between allelic variants as a mechanism for how genetic variation gives rise to certain phenotypes.
As we are interested in the development of computational approaches to protein sequence and structure analysis, we offer web based programs and software that we have developed. Projects include the development of techniques to search for homologous proteins based on data generated by mass spectrometry (MS-BLAST), a program to predict the functional effect of missense mutations (PolyPhen ), and a program for analysis of complex protein mixtures (Eagle Eye).
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Education: |
Moscow Institute of Physics & Technology , 1997, Ph.D. Moscow Institute of Physics and Technology , 1994, MS
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Publications (Pulled from Harvard Catalyst Profiles):
1. Chandonia JM, Adhikari A, Carraro M, Chhibber A, Cutting GR, Fu Y, Gasparini A, Jones DT, Kramer A, Kundu K, Lam HYK, Leonardi E, Moult J, Pal LR, Searls DB, Shah S, Sunyaev S, Tosatto SCE, Yin Y, Buckley BA. Lessons from the CAGI-4 Hopkins clinical panel challenge. Hum Mutat. 2017 Apr 11.
2. Cassa CA, Weghorn D, Balick DJ, Jordan DM, Nusinow D, Samocha KE, O'Donnell-Luria A, MacArthur DG, Daly MJ, Beier DR, Sunyaev SR. Estimating the selective effects of heterozygous protein-truncating variants from human exome data. Nat Genet. 2017 May; 49(5):806-810.
3. Chun S, Casparino A, Patsopoulos NA, Croteau-Chonka DC, Raby BA, De Jager PL, Sunyaev SR, Cotsapas C. Limited statistical evidence for shared genetic effects of eQTLs and autoimmune-disease-associated loci in three major immune-cell types. Nat Genet. 2017 Apr; 49(4):600-605.
4. Wang H, Cade BE, Chen H, Gleason KJ, Saxena R, Feng T, Larkin EK, Vasan RS, Lin H, Patel SR, Tracy RP, Liu Y, Gottlieb DJ, Below JE, Hanis CL, Petty LE, Sunyaev SR, Frazier-Wood AC, Rotter JI, Post W, Lin X, Redline S, Zhu X. Variants in angiopoietin-2 (ANGPT2) contribute to variation in nocturnal oxyhaemoglobin saturation level. Hum Mol Genet. 2016 Dec 01; 25(23):5244-5253.
5. Zou J, Valiant G, Valiant P, Karczewski K, Chan SO, Samocha K, Lek M, Sunyaev S, Daly M, MacArthur DG. Quantifying unobserved protein-coding variants in human populations provides a roadmap for large-scale sequencing projects. Nat Commun. 2016 Oct 31; 7:13293.
6. Cade BE, Chen H, Stilp AM, Gleason KJ, Sofer T, Ancoli-Israel S, Arens R, Bell GI, Below JE, Bjonnes AC, Chun S, Conomos MP, Evans DS, Johnson WC, Frazier-Wood AC, Lane JM, Larkin EK, Loredo JS, Post WS, Ramos AR, Rice K, Rotter JI, Shah NA, Stone KL, Taylor KD, Thornton TA, Tranah GJ, Wang C, Zee PC, Hanis CL, Sunyaev SR, Patel SR, Laurie CC, Zhu X, Saxena R, Lin X, Redline S. Genetic Associations with Obstructive Sleep Apnea Traits in Hispanic/Latino Americans. Am J Respir Crit Care Med. 2016 Oct 01; 194(7):886-897.
7. Sul JH, Cade BE, Cho MH, Qiao D, Silverman EK, Redline S, Sunyaev S. Increasing Generality and Power of Rare-Variant Tests by Utilizing Extended Pedigrees. Am J Hum Genet. 2016 Oct 06; 99(4):846-859.
8. Lenz TL, Spirin V, Jordan DM, Sunyaev SR. Excess of Deleterious Mutations around HLA Genes Reveals Evolutionary Cost of Balancing Selection. Mol Biol Evol. 2016 Oct; 33(10):2555-64.
9. Oetting WS, Brenner SE, Brookes AJ, Greenblatt MS, Hart RK, Karchin R, Sunyaev SR, Taschner PE. Pathogenicity Interpretation in the Age of Precision Medicine: The 2015 Annual Scientific Meeting of the Human Genome Variation Society. Hum Mutat. 2016 Apr; 37(4):406-11.
10. Savova V, Chun S, Sohail M, McCole RB, Witwicki R, Gai L, Lenz TL, Wu CT, Sunyaev SR, Gimelbrant AA. Genes with monoallelic expression contribute disproportionately to genetic diversity in humans. Nat Genet. 2016 Mar; 48(3):231-7.
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