Detecting selection in immunoglobulin sequences

Mohamed Uduman, Gur Yaari, Uri Hershberg, Jacob A. Stern, Mark J. Shlomchik, Steven H. Kleinstein

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

The ability to detect selection by analyzing mutation patterns in experimentally derived immunoglobulin (Ig) sequences is a critical part of many studies. Such techniques are useful not only for understanding the response to pathogens, but also to determine the role of antigen-driven selection in autoimmunity, B cell cancers and the diversification of pre-immune repertoires in certain species. Despite its importance, quantifying selection in experimentally derived sequences is fraught with difficulties. The necessary parameters for statistical tests (such as the expected frequency of replacement mutations in the absence of selection) are non-trivial to calculate, and results are not easily interpretable when analyzing more than a handful of sequences. We have developed a web server that implements our previously proposed Focused binomial test for detecting selection. Several features are integrated into the web site in order to facilitate analysis, including V(D)J germline segment identification with IMGT alignment, batch submission of sequences and integration of additional test statistics proposed by other groups. We also implement a Z-score-based statistic that increases the power of detecting selection while maintaining specificity, and further allows for the combined analysis of sequences from different germlines. The tool is freely available at http://clip.med.yale.edu/selection.

Original languageEnglish
Pages (from-to)W499-W504
JournalNucleic Acids Research
Volume39
Issue numberSUPPL. 2
DOIs
StatePublished - 1 Jul 2011
Externally publishedYes

Bibliographical note

Funding Information:
National Institutes of Health (R03AI092379-01) (in part). Funding for open access charge: National Institutes of Health (R03AI092379-01).

Fingerprint

Dive into the research topics of 'Detecting selection in immunoglobulin sequences'. Together they form a unique fingerprint.

Cite this