title: Comprehensive evaluation of fusion transcript detection algorithms and a meta-caller to combine top performing methods in paired-end RNA-seq data.
abstract: BACKGROUND
  Fusion transcripts are formed by either fusion genes (DNA level) or trans-splicing events (RNA level). They have been recognized as a promising tool for diagnosing, subtyping and treating cancers. RNA-seq has become a precise and efficient standard for genome-wide screening of such aberration events. Many fusion transcript detection algorithms have been developed for paired-end RNA-seq data but their performance has not been comprehensively evaluated to guide practitioners. In this paper, we evaluated 15 popular algorithms by their precision and recall trade-off, accuracy of supporting reads and computational cost. We further combine top-performing methods for improved ensemble detection.
  
  
  RESULTS
  Fifteen fusion transcript detection tools were compared using three synthetic data sets under different coverage, read length, insert size and background noise, and three real data sets with selected experimental validations. No single method dominantly performed the best but SOAPfuse generally performed well, followed by FusionCatcher and JAFFA. We further demonstrated the potential of a meta-caller algorithm by combining top performing methods to re-prioritize candidate fusion transcripts with high confidence that can be followed by experimental validation.
  
  
  CONCLUSIONS
  Our result provides insightful recommendations when applying individual tool or combining top performers to identify fusion transcript candidates.
authors.affiliation: Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261, USA Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Biomedical Science Tower 3, 3501 Fifth Avenue, Pittsburgh, PA 15213, USA.
authors.forename: Silvia
authors.initials: S
authors.lastname: Liu
authors.affiliation: Institute of Biomedical Informatics, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Beitou District, Taipei 112, Taiwan.
authors.forename: Wei-Hsiang
authors.initials: WH
authors.lastname: Tsai
authors.affiliation: Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261, USA Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Biomedical Science Tower 3, 3501 Fifth Avenue, Pittsburgh, PA 15213, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261, USA.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261, USA.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Huo
authors.affiliation: Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261, USA.
authors.forename: SungHwan
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261, USA.
authors.forename: Tianzhou
authors.initials: T
authors.lastname: Ma
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Beitou District, Taipei 112, Taiwan.
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Chang
authors.affiliation: Molecular Pharmacology, School of Medicine, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
authors.forename: Nolan Michael
authors.initials: NM
authors.lastname: Priedigkeit
authors.affiliation: Magee-Women's Research Institute, 204 Craft Avenue, Pittsburgh, PA 15213, USA.
authors.forename: Adrian V
authors.initials: AV
authors.lastname: Lee
authors.affiliation: Department of Pathology, School of Medicine, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Luo
authors.affiliation: Institute of Biomedical Informatics, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Beitou District, Taipei 112, Taiwan Institute of Microbiology and Immunology, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Beitou District, Taipei 112, Taiwan Center for Systems and Synthetic Biology, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Beitou District, Taipei 112, Taiwan hwwang@ym.edu.tw.
authors.forename: Hsei-Wei
authors.initials: HW
authors.lastname: Wang
authors.affiliation: Institute of Biomedical Informatics, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Beitou District, Taipei 112, Taiwan Center for Systems and Synthetic Biology, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Beitou District, Taipei 112, Taiwan ifchung@ym.edu.tw.
authors.forename: I-Fang
authors.initials: IF
authors.lastname: Chung
authors.affiliation: Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261, USA Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Biomedical Science Tower 3, 3501 Fifth Avenue, Pittsburgh, PA 15213, USA ctseng@pitt.edu.
authors.forename: George C
authors.initials: GC
authors.lastname: Tseng
mesh_terms: D000465:Algorithms; D017398:Alternative Splicing; D020869:Gene Expression Profiling; D050939:Gene Fusion; D006801:Humans; D050506:Mutant Chimeric Proteins / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D017423:Sequence Analysis, RNA; D012984:Software
chemical_list: D050506:Mutant Chimeric Proteins; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger