title: RVboost: RNA-seq variants prioritization using a boosting method.
abstract: BACKGROUND
  RNA-seq has become the method of choice to quantify genes and exons, discover novel transcripts and detect fusion genes. However, reliable variant identification from RNA-seq data remains challenging because of the complexities of the transcriptome, the challenges of accurately mapping exon boundary spanning reads and the bias introduced during the sequencing library preparation.
  
  
  METHODS
  We developed RVboost, a novel method specific for RNA variant prioritization. RVboost uses several attributes unique in the process of RNA library preparation, sequencing and RNA-seq data analyses. It uses a boosting method to train a model of 'good quality' variants using common variants from HapMap, and prioritizes and calls the RNA variants based on the trained model. We packaged RVboost in a comprehensive workflow, which integrates tools of variant calling, annotation and filtering.
  
  
  RESULTS
  RVboost consistently outperforms the variant quality score recalibration from the Genome Analysis Tool Kit and the RNA-seq variant-calling pipeline SNPiR in 12 RNA-seq samples using ground-truth variants from paired exome sequencing data. Several RNA-seq-specific attributes were identified as critical to differentiate true and false variants, including the distance of the variant positions to exon boundaries, and the percent of the reads supporting the variant in the first six base pairs. The latter identifies false variants introduced by the random hexamer priming during the library construction.
  
  
  METHODS
  The RVboost package is implemented to readily run in Mac or Linux environments. The software and user manual are available at http://bioinformaticstools.mayo.edu/research/rvboost/.
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester MN 55905, Department of Health Sciences Research, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, Department of Laboratory Medicine and Pathology, Division of Hematology, Department of Internal Medicine, Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester MN 55905 and Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester MN 55905, Department of Health Sciences Research, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, Department of Laboratory Medicine and Pathology, Division of Hematology, Department of Internal Medicine, Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester MN 55905 and Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, USA.
authors.forename: Jaime I
authors.initials: JI
authors.lastname: Davila
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester MN 55905, Department of Health Sciences Research, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, Department of Laboratory Medicine and Pathology, Division of Hematology, Department of Internal Medicine, Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester MN 55905 and Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, USA.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Baheti
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester MN 55905, Department of Health Sciences Research, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, Department of Laboratory Medicine and Pathology, Division of Hematology, Department of Internal Medicine, Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester MN 55905 and Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, USA.
authors.forename: Aditya V
authors.initials: AV
authors.lastname: Bhagwate
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester MN 55905, Department of Health Sciences Research, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, Department of Laboratory Medicine and Pathology, Division of Hematology, Department of Internal Medicine, Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester MN 55905 and Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, USA.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester MN 55905, Department of Health Sciences Research, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, Department of Laboratory Medicine and Pathology, Division of Hematology, Department of Internal Medicine, Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester MN 55905 and Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, USA.
authors.forename: Jean-Pierre A
authors.initials: JP
authors.lastname: Kocher
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester MN 55905, Department of Health Sciences Research, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, Department of Laboratory Medicine and Pathology, Division of Hematology, Department of Internal Medicine, Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester MN 55905 and Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Slager
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester MN 55905, Department of Health Sciences Research, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, Department of Laboratory Medicine and Pathology, Division of Hematology, Department of Internal Medicine, Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester MN 55905 and Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Feldman
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester MN 55905, Department of Health Sciences Research, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, Department of Laboratory Medicine and Pathology, Division of Hematology, Department of Internal Medicine, Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester MN 55905 and Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, USA.
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Novak
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester MN 55905, Department of Health Sciences Research, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, Department of Laboratory Medicine and Pathology, Division of Hematology, Department of Internal Medicine, Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester MN 55905 and Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester MN 55905, Department of Health Sciences Research, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, Department of Laboratory Medicine and Pathology, Division of Hematology, Department of Internal Medicine, Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester MN 55905 and Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, USA.
authors.forename: E Aubrey
authors.initials: EA
authors.lastname: Thompson
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester MN 55905, Department of Health Sciences Research, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, Department of Laboratory Medicine and Pathology, Division of Hematology, Department of Internal Medicine, Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester MN 55905 and Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road South, Jacksonville FL 32224, USA.
authors.forename: Yan W
authors.initials: YW
authors.lastname: Asmann
mesh_terms: D059472:Exome; D005091:Exons; D020869:Gene Expression Profiling; D014644:Genetic Variation; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D017423:Sequence Analysis, RNA / Q000379:methods*; D012984:Software