A novel pipeline for identification and prioritization of gene fusions in Patient-derived xenografts of metastatic colorectal cancer

Paciello Giulia, Andrea Acquaviva, Consalvo Petti, Claudio Isella, Enzo Medico, Elisa Ficarra

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Metastatic spread to the liver is a frequent complication of colorectal cancer (CRC), occurring in almost half of the cases, for which personalized treatment strategies are highly desirable. To this aim, it has been proven that patient-derived mouse xenografts (PDX) of liver-metastatic CRC can be used to discover new therapeutic targets and determinants of drug resistance. To identify gene fusions in RNA-Seq data obtained from such PDX samples, we propose a novel pipeline that tackles the following issues: (i) discriminating human from murine RNA, to filter out transcripts contributed by the mouse stroma that supports the PDX; (ii) increasing sensitivity in case of suboptimal RNA-Seq coverage; (iii) prioritizing the detected chimeric transcripts by molecular features of the fusion and by functional relevance of the involved genes; (iv) providing appropriate sequence information for subsequent validation of the identified fusions. The pipeline, built on top of Chimerascan(R.Iyer, 2011) and deFuse(McPherson, 2011) aligner tools, was successfully applied to RNASeq data from 11 PDX samples. Among the 299 fusion genes identified by the aforementioned softwares, five were selected since passed all the filtering stages implemented into the proposed pipeline resulting as biologically relevant fusions. Three of them were experimentally confirmed.

Original languageEnglish
Title of host publicationBIOINFORMATICS 2014 - 5th Int. Conf. on Bioinformatics Models, Methods and Algorithms, Proceedings; Part of 7th Int. Joint Conference on Biomedical Engineering Systems and Technologies, BIOSTEC 2014
PublisherSciTePress
Pages142-148
Number of pages7
ISBN (Print)9789897580123
Publication statusPublished - 2014
Event5th International Conference on Bioinformatics Models, Methods and Algorithms, BIOINFORMATICS 2014 - Part of 7th International Joint Conference on Biomedical Engineering Systems and Technologies, BIOSTEC 2014 - Angers, Loire Valley, France
Duration: Mar 3 2014Mar 6 2014

Other

Other5th International Conference on Bioinformatics Models, Methods and Algorithms, BIOINFORMATICS 2014 - Part of 7th International Joint Conference on Biomedical Engineering Systems and Technologies, BIOSTEC 2014
CountryFrance
CityAngers, Loire Valley
Period3/3/143/6/14

Keywords

  • Artifacts
  • Metastatic Colorectal Cancer
  • Patient-derived Mouse Xenografts
  • RNA-sequencing

ASJC Scopus subject areas

  • Biomedical Engineering
  • Modelling and Simulation

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