title: Computational identification of insertional mutagenesis targets for cancer gene discovery.
abstract: Insertional mutagenesis is a potent forward genetic screening technique used to identify candidate cancer genes in mouse model systems. An important, yet unresolved issue in the analysis of these screens, is the identification of the genes affected by the insertions. To address this, we developed Kernel Convolved Rule Based Mapping (KC-RBM). KC-RBM exploits distance, orientation and insertion density across tumors to automatically map integration sites to target genes. We perform the first genome-wide evaluation of the association of insertion occurrences with aberrant gene expression of the predicted targets in both retroviral and transposon data sets. We demonstrate the efficiency of KC-RBM by showing its superior performance over existing approaches in recovering true positives from a list of independently, manually curated cancer genes. The results of this work will significantly enhance the accuracy and speed of cancer gene discovery in forward genetic screens. KC-RBM is available as R-package.
authors.affiliation: Bioinformatics and Statistics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
authors.forename: Johann
authors.initials: J
authors.lastname: de Jong
authors.forename: Jeroen
authors.initials: J
authors.lastname: de Ridder
authors.forename: Louise
authors.initials: L
authors.lastname: van der Weyden
authors.forename: Ning
authors.initials: N
authors.lastname: Sun
authors.forename: Miranda
authors.initials: M
authors.lastname: van Uitert
authors.forename: Anton
authors.initials: A
authors.lastname: Berns
authors.forename: Maarten
authors.initials: M
authors.lastname: van Lohuizen
authors.forename: Jos
authors.initials: J
authors.lastname: Jonkers
authors.forename: David J
authors.initials: DJ
authors.lastname: Adams
authors.forename: Lodewyk F A
authors.initials: LF
authors.lastname: Wessels
mesh_terms: D000818:Animals; D002874:Chromosome Mapping / Q000379:methods*; D019295:Computational Biology / Q000379:methods; D004251:DNA Transposable Elements; D015870:Gene Expression; D052138:Genes, Neoplasm; D009052:Leukemia Virus, Murine / Q000235:genetics; D051379:Mice; D016254:Mutagenesis, Insertional
chemical_list: D004251:DNA Transposable Elements