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Authors: Paciello Giulia 1 ; Andrea Acquaviva 1 ; Consalvo Petti 2 ; Claudio Isella 2 ; Enzo Medico 3 and Elisa Ficarra 1

Affiliations: 1 Politecnico di Torino, Italy ; 2 Institute for Cancer Research at Candiolo (IRCC), Italy ; 3 Institute for Cancer Research at Candiolo (IRCC) and Universita’ di Torino, Italy

ISBN: 978-989-758-012-3

Keyword(s): RNA-sequencing, Metastatic Colorectal Cancer, Patient-derived Mouse Xenografts, Artifacts.

Related Ontology Subjects/Areas/Topics: Bioinformatics ; Biomedical Engineering ; Genomics and Proteomics ; Next Generation Sequencing

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. (More)

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Paper citation in several formats:
Giulia, P.; Acquaviva, A.; Petti, C.; Isella, C.; Medico, E. and Ficarra, E. (2014). A Novel Pipeline for Identification and Prioritization of Gene Fusions in Patient-derived Xenografts of Metastatic Colorectal Cancer.In Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms - Volume 1: BIOINFORMATICS, (BIOSTEC 2014) ISBN 978-989-758-012-3, pages 142-148. DOI: 10.5220/0004799401420148

@conference{bioinformatics14,
author={Paciello Giulia. and Andrea Acquaviva. and Consalvo Petti. and Claudio Isella. and Enzo Medico. and Elisa Ficarra.},
title={A Novel Pipeline for Identification and Prioritization of Gene Fusions in Patient-derived Xenografts of Metastatic Colorectal Cancer},
booktitle={Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms - Volume 1: BIOINFORMATICS, (BIOSTEC 2014)},
year={2014},
pages={142-148},
publisher={SciTePress},
organization={INSTICC},
doi={10.5220/0004799401420148},
isbn={978-989-758-012-3},
}

TY - CONF

JO - Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms - Volume 1: BIOINFORMATICS, (BIOSTEC 2014)
TI - A Novel Pipeline for Identification and Prioritization of Gene Fusions in Patient-derived Xenografts of Metastatic Colorectal Cancer
SN - 978-989-758-012-3
AU - Giulia, P.
AU - Acquaviva, A.
AU - Petti, C.
AU - Isella, C.
AU - Medico, E.
AU - Ficarra, E.
PY - 2014
SP - 142
EP - 148
DO - 10.5220/0004799401420148

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