Intensification: A Resource for Amplifying Population-Genetic Signals with Protein Repeats.

TitleIntensification: A Resource for Amplifying Population-Genetic Signals with Protein Repeats.
Publication TypeJournal Article
Year of Publication2017
AuthorsChen, J, Wang, B, Regan, L, Gerstein, M
JournalJ Mol Biol
Volume429
Issue3
Pagination435-445
Date Published2017 Feb 03
ISSN1089-8638
Abstract

Large-scale genome sequencing holds great promise for the interpretation of protein structures through the discovery of many, rare functional variants in the human population. However, because protein-coding regions are under high selective constraints, these variants occur at low frequencies, such that there is often insufficient statistics for downstream calculations. To address this problem, we develop the Intensification approach, which uses the modular structure of repeat protein domains to amplify signals of selection from population genetics and traditional interspecies conservation. In particular, we are able to aggregate variants at the codon level to identify important positions in repeat domains that show strong conservation signals. This allows us to compare conservation over different evolutionary timescales. It also enables us to visualize population-genetic measures on protein structures. We make available the Intensification results as an online resource (http://intensification.gersteinlab.org) and illustrate the approach through a case study on the tetratricopeptide repeat.

DOI10.1016/j.jmb.2016.12.003
Alternate JournalJ. Mol. Biol.
PubMed ID27939289
Grant ListR01 HG008126 / HG / NHGRI NIH HHS / United States
U54 HG006504 / HG / NHGRI NIH HHS / United States