New methods for finding common insertion sites and co-occurring common insertion sites in transposon- and virus-based genetic screens
| Autor: | David A. Largaespada, Haoyu Yu, Robert T. Cormier, Tracy L. Bergemann, Kevin A. T. Silverstein, Yun Chen, Michael Steinbach, Jesse Erdmann, Timothy K. Starr |
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| Rok vydání: | 2012 |
| Předmět: |
Transposable element
Candidate gene Biology medicine.disease_cause Genome Insertional mutagenesis Mice 03 medical and health sciences 0302 clinical medicine Genetics medicine Animals Humans Poisson Distribution Gene Gastrointestinal Neoplasms 030304 developmental biology 0303 health sciences Mutation Computational Biology 3. Good health Mutagenesis Insertional Cell Transformation Neoplastic Retroviridae 030220 oncology & carcinogenesis DNA Transposable Elements Regression Analysis Candidate Disease Gene Monte Carlo Method Genes Neoplasm Genetic screen |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkr1295 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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