Shamil SunyaevDivision of Genetics, Dept. of Medicine
Brigham & Women's Hospital and Harvard Medical School
New Research Building, Room 466B (4th Floor)
77 Avenue Louis Pasteur, Boston, MA 02115
tel: (617) 525-4735; fax: (617) 525-4705
We are a computational biology laboratory. We develop and apply computational methods to pursue various problems in fields of genetics, genomics and proteomics. Our main interest is to analyse the population genetic variation and the genome divergence between species with the major focus on the protein coding regions. The effect of amino acid substitutions on function and structure of proteins can be frequently understood and even predicted via comparative sequence analysis and analysis of the protein structure. We relate the above functional studies to the evolutionary process of natural selection in order to track the evolution of proteins at the molecular level. Large-scale statistical approaches are suitable to study the way new mutations, genetic drift and natural selection shape the population genetic variation and how this variation once becomes a species divergence. The results of structural and evolutionary studies can be further applied to the data on human genetic polymorphisms with the goal to understand the complex mechanisms of inheritance and most importantly the genetic basis of human multifactorial diseases.
Our future effort will be directed towards the development of methods to extract knowledge on functionality and evolution from the novel massive data on closely related genomes and population genetic variants. We are hoping to reveal epistatic interactions between allelic variants and understand their molecular basis, thus getting closer to the understanding of the interplay of genetic variants to give rise to phenotypes. We are planning to utilise the knowledge gained to study the data on genotypes of patients suffering from common complex disorders through the established collaborations with groups involved in large medical genetics research projects.
Additionally, we are interested in development of computational approaches to protein sequence and structure analysis. Recent projects include development of techniques to search for homologous proteins based on data generated by mass spectrometry; constructing statistical framework to search for structural similarities between protein active and binding sites; development of a novel sequence alignment algorithm.
Kryukov GV, Schmidt S, & Sunyaev S. (2005). Small fitness effect of mutations in highly conserved non-coding regions. Hum Mol Genet. 14(15): 2221-9.
Jordan IK, Kondrashov FA, Adzhubei IA, Wolf YI, Koonin EV, Kondrashov AS, & Sunyaev S. A universal trend of amino acid gain and loss in protein evolution. Nature. (2005) 433(7026):633-8.
Asthana S, Schmidt S, & Sunyaev S. A limited role for balancing selection. Trends Genet. (2005) 21(1): 30-2.
Bazykin GA, Kondrashov FA, Ogurtsov AY, Sunyaev S, & Kondrashov AS. Positive selection at sites of multiple amino acid replacements since rat-mouse divergence. Nature (2004) 429(6991):558-62.
Sunyaev S, Liska AJ, Golod A, Shevchenko A. & Shevchenko A. MultiTag: multiple error-tolerant sequence tag search for the sequence-similarity identification of proteins by mass spectrometry. Anal Chem. (2003) 75(6):1307-15.
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