Representation of sequence evolution in the framework of birth–death processes. From: Kryukov GV, Schmidt S, and Sunyaev S, Small fitness effect of mutations in highly conserved non-coding regions, Hum Mol Genet 2005.
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).
Courses and Affiliations
We are involved in the following graduate programs:
Biological & Biomedical Sciences Program at the Division of Medical Sciences, Harvard Medical School
The Harvard University Biophysics Program
The Harvard-MIT Division of Health Sciences & Technology Programs
Courses taught: (link coming)