title: Simulation-based comprehensive benchmarking of RNA-seq aligners.
abstract: Alignment is the first step in most RNA-seq analysis pipelines, and the accuracy of downstream analyses depends heavily on it. Unlike most steps in the pipeline, alignment is particularly amenable to benchmarking with simulated data. We performed a comprehensive benchmarking of 14 common splice-aware aligners for base, read, and exon junction-level accuracy and compared default with optimized parameters. We found that performance varied by genome complexity, and accuracy and popularity were poorly correlated. The most widely cited tool underperforms for most metrics, particularly when using default settings.
authors.affiliation: Department of Information Engineering, University of Padova, Padua, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Baruzzo
authors.affiliation: Institute for Translational Medicine and Therapeutics (ITMAT), University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Katharina E
authors.initials: KE
authors.lastname: Hayer
authors.affiliation: Institute for Translational Medicine and Therapeutics (ITMAT), University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Department of Information Engineering, University of Padova, Padua, Italy.
authors.forename: Barbara
authors.identifier: 0000-0001-8415-4688
authors.initials: B
authors.lastname: Di Camillo
authors.affiliation: Institute for Translational Medicine and Therapeutics (ITMAT), University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Garret A
authors.initials: GA
authors.lastname: FitzGerald
authors.affiliation: Institute for Translational Medicine and Therapeutics (ITMAT), University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Grant
mesh_terms: D019985:Benchmarking; D003198:Computer Simulation; D005091:Exons; D015894:Genome, Human; D006801:Humans; D007438:Introns; D058977:Molecular Sequence Annotation; D010963:Plasmodium falciparum / Q000235:genetics*; D011110:Polymorphism, Genetic; D012326:RNA Splicing; D016415:Sequence Alignment / Q000379:methods*; D017423:Sequence Analysis, RNA / Q000379:methods*; D012984:Software