title: Pegasus: a comprehensive annotation and prediction tool for detection of driver gene fusions in cancer.
abstract: BACKGROUND
  The extraordinary success of imatinib in the treatment of BCR-ABL1 associated cancers underscores the need to identify novel functional gene fusions in cancer. RNA sequencing offers a genome-wide view of expressed transcripts, uncovering biologically functional gene fusions. Although several bioinformatics tools are already available for the detection of putative fusion transcripts, candidate event lists are plagued with non-functional read-through events, reverse transcriptase template switching events, incorrect mapping, and other systematic errors. Such lists lack any indication of oncogenic relevance, and they are too large for exhaustive experimental validation.
  
  
  RESULTS
  We have designed and implemented a pipeline, Pegasus, for the annotation and prediction of biologically functional gene fusion candidates. Pegasus provides a common interface for various gene fusion detection tools, reconstruction of novel fusion proteins, reading-frame-aware annotation of preserved/lost functional domains, and data-driven classification of oncogenic potential. Pegasus dramatically streamlines the search for oncogenic gene fusions, bridging the gap between raw RNA-Seq data and a final, tractable list of candidates for experimental validation.
  
  
  CONCLUSIONS
  We show the effectiveness of Pegasus in predicting new driver fusions in 176 RNA-Seq samples of glioblastoma multiforme (GBM) and 23 cases of anaplastic large cell lymphoma (ALCL).
authors.affiliation: Department of Biomedical Informatics, Columbia University, 1130 St. Nicholas Ave, New York, NY, 10032, USA. fa2306@columbia.edu.|Center for Computational Biology and Bioinformatics, Columbia University, 1130 St. Nicholas Ave, New York, NY, 10032, USA. fa2306@columbia.edu.|Department of Control and Computer Engineering, Politecnico di Torino, Torino, 10129, Italy. fa2306@columbia.edu.
authors.forename: Francesco
authors.initials: F
authors.lastname: Abate
authors.affiliation: Center for Computational Biology and Bioinformatics, Columbia University, 1130 St. Nicholas Ave, New York, NY, 10032, USA. siz2102@columbia.edu.
authors.forename: Sakellarios
authors.initials: S
authors.lastname: Zairis
authors.affiliation: Department of Control and Computer Engineering, Politecnico di Torino, Torino, 10129, Italy. elisa.ficarra@polito.it.
authors.forename: Elisa
authors.initials: E
authors.lastname: Ficarra
authors.affiliation: Department of Control and Computer Engineering, Politecnico di Torino, Torino, 10129, Italy. andrea.acquaviva@polito.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Acquaviva
authors.affiliation: Center for Computational Biology and Bioinformatics, Columbia University, 1130 St. Nicholas Ave, New York, NY, 10032, USA. chris.wiggins@columbia.edu.|Department of Applied Physics and Applied Mathematics, The Fu Foundation School for Engineering and Applied Sciences, Columbia University, 500 W. 120th Street, Mudd 200, MC 4701, New York, New York, 10027, USA. chris.wiggins@columbia.edu.|Institute for Data Sciences and Engineering, Columbia University, 500 W. 120th Street, Mudd 524, New York, New York, 10027, USA. chris.wiggins@columbia.edu.
authors.forename: Chris H
authors.initials: CH
authors.lastname: Wiggins
authors.affiliation: Institute for Cancer Genetics, Columbia University Medical Center, New York, New York, USA. vf2206@columbia.edu.
authors.forename: Veronique
authors.initials: V
authors.lastname: Frattini
authors.affiliation: Institute for Cancer Genetics, Columbia University Medical Center, New York, New York, USA. al2179@columbia.edu.
authors.forename: Anna
authors.initials: A
authors.lastname: Lasorella
authors.affiliation: Institute for Cancer Genetics, Columbia University Medical Center, New York, New York, USA. ai2102@columbia.edu.
authors.forename: Antonio
authors.initials: A
authors.lastname: Iavarone
authors.affiliation: Department of Pathology, Center for Experimental Research and Medical Studies, Laboratory of Functional Genomics, University of Torino, Torino, Italy. ggi9001@med.cornell.edu.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Inghirami
authors.affiliation: Department of Biomedical Informatics, Columbia University, 1130 St. Nicholas Ave, New York, NY, 10032, USA. rabadan@dbmi.columbia.edu.|Center for Computational Biology and Bioinformatics, Columbia University, 1130 St. Nicholas Ave, New York, NY, 10032, USA. rabadan@dbmi.columbia.edu.
authors.forename: Raul
authors.initials: R
authors.lastname: Rabadan
mesh_terms: D019295:Computational Biology / Q000379:methods*; D030541:Databases, Genetic; D003663:Decision Trees; D050939:Gene Fusion / Q000235:genetics*; D006801:Humans; D058977:Molecular Sequence Annotation / Q000379:methods*; D009369:Neoplasms / Q000235:genetics*; D012984:Software