Bellerophontes: an RNA-Seq data analysis framework for chimeric transcripts discovery based on accurate fusion model

• Published in: Bioinformatics 2012-08, Vol.28 (16), p.2114-2121
• Main Authors: ABATE, Francesco, ACQUAVIVA, Andrea, MACII, Enrico, PACIELLO, Giulia, FOTI, Carmelo, FICARRA, Elisa, FERRARINI, Alberto, DELLEDONNE, Massimo, LACOBUCCI, Ilaria, SOVERINI, Simona, MARTINELLI, Giovanni
• Format: Article
• Language: English
• Subjects: Algorithms; Biological and medical sciences; Computational Biology - methods; Fundamental and applied biological sciences. Psychology; Gene Fusion; General aspects; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Mathematics in biology. Statistical analysis. Models. Metrology. Data processing in biology (general aspects); RNA - genetics; RNA Splicing; Sequence Alignment; Sequence Analysis, RNA - methods; Software
• ISSN: 1367-4803; 1367-4811; 1460-2059
• DOI: 10.1093/bioinformatics/bts334

Next-generation sequencing technology allows the detection of genomic structural variations, novel genes and transcript isoforms from the analysis of high-throughput data. In this work, we propose a new framework for the detection of fusion transcripts through short paired-end reads which integrates splicing-driven alignment and abundance estimation analysis, producing a more accurate set of reads supporting the junction discovery and taking into account also not annotated transcripts. Bellerophontes performs a selection of putative junctions on the basis of a match to an accurate gene fusion model. We report the fusion genes discovered by the proposed framework on experimentally validated biological samples of chronic myelogenous leukemia (CML) and on public NCBI datasets, for which Bellerophontes is able to detect the exact junction sequence. With respect to state-of-art approaches, Bellerophontes detects the same experimentally validated fusions, however, it is more selective on the total number of detected fusions and provides a more accurate set of spanning reads supporting the junctions. We finally report the fusions involving non-annotated transcripts found in CML samples. Bellerophontes JAVA/Perl/Bash software implementation is free and available at http://eda.polito.it/bellerophontes/.