title: State-of-the-art fusion-finder algorithms sensitivity and specificity.
abstract: BACKGROUND
  Gene fusions arising from chromosomal translocations have been implicated in cancer. RNA-seq has the potential to discover such rearrangements generating functional proteins (chimera/fusion). Recently, many methods for chimeras detection have been published. However, specificity and sensitivity of those tools were not extensively investigated in a comparative way.
  
  
  RESULTS
  We tested eight fusion-detection tools (FusionHunter, FusionMap, FusionFinder, MapSplice, deFuse, Bellerophontes, ChimeraScan, and TopHat-fusion) to detect fusion events using synthetic and real datasets encompassing chimeras. The comparison analysis run only on synthetic data could generate misleading results since we found no counterpart on real dataset. Furthermore, most tools report a very high number of false positive chimeras. In particular, the most sensitive tool, ChimeraScan, reports a large number of false positives that we were able to significantly reduce by devising and applying two filters to remove fusions not supported by fusion junction-spanning reads or encompassing large intronic regions.
  
  
  CONCLUSIONS
  The discordant results obtained using synthetic and real datasets suggest that synthetic datasets encompassing fusion events may not fully catch the complexity of RNA-seq experiment. Moreover, fusion detection tools are still limited in sensitivity or specificity; thus, there is space for further improvement in the fusion-finder algorithms.
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126 Torino, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Carrara
authors.forename: Marco
authors.initials: M
authors.lastname: Beccuti
authors.forename: Fulvio
authors.initials: F
authors.lastname: Lazzarato
authors.forename: Federica
authors.initials: F
authors.lastname: Cavallo
authors.forename: Francesca
authors.initials: F
authors.lastname: Cordero
authors.forename: Susanna
authors.initials: S
authors.lastname: Donatelli
authors.forename: Raffaele A
authors.initials: RA
authors.lastname: Calogero
mesh_terms: D002678:Chimera / Q000235:genetics; D050939:Gene Fusion; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D017423:Sequence Analysis, RNA; D012984:Software; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D015514:Oncogene Proteins, Fusion
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