New methods for finding common insertion sites and co-occurring common insertion sites in transposon-and virus-based genetic screens

Tracy L. Bergemann, Timothy K. Starr, Haoyu Yu, Michael Steinbach, Jesse Erdmann, Yun Chen, Robert T. Cormier, David A. Largaespada, Kevin A T Silverstein

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Insertional mutagenesis screens in mice are used to identify individual genes that drive tumor formation. In these screens, candidate cancer genes are identified if their genomic location is proximal to a common insertion site (CIS) defined by high rates of transposon or retroviral insertions in a given genomic window. In this article, we describe a new method for defining CISs based on a Poisson distribution, the Poisson Regression Insertion Model, and show that this new method is an improvement over previously described methods. We also describe a modification of the method that can identify pairs and higher orders of co-occurring common insertion sites. We apply these methods to two data sets, one generated in a transposon-based screen for gastrointestinal tract cancer genes and another based on the set of retroviral insertions in the Retroviral Tagged Cancer Gene Database. We show that the new methods identify more relevant candidate genes and candidate gene pairs than found using previous methods. Identification of the biologically relevant set of mutations that occur in a single cell and cause tumor progression will aid in the rational design of single and combinatorial therapies in the upcoming age of personalized cancer therapy.

Original languageEnglish (US)
Pages (from-to)3822-3833
Number of pages12
JournalNucleic acids research
Volume40
Issue number9
DOIs
StatePublished - May 2012

Bibliographical note

Funding Information:
National Institute of Health (grant number R01-CA113636); Post-doctoral Fellowship from the American Cancer Society (grant number PF-06– 292-01-MGO to T.K.S.); NIH Pathway to Independence award (grant number 4 R00CA151672-03 to T.K.S.) and National Science Foundation (grant number III:0916439). Funding for open access charge: University of Minnesota.

Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.

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