title: Towards accurate detection and genotyping of expressed variants from whole transcriptome sequencing data.
abstract: BACKGROUND
  Massively parallel transcriptome sequencing (RNA-Seq) is becoming the method of choice for studying functional effects of genetic variability and establishing causal relationships between genetic variants and disease. However, RNA-Seq poses new technical and computational challenges compared to genome sequencing. In particular, mapping transcriptome reads onto the genome is more challenging than mapping genomic reads due to splicing. Furthermore, detection and genotyping of single nucleotide variants (SNVs) requires statistical models that are robust to variability in read coverage due to unequal transcript expression levels.
  
  
  RESULTS
  In this paper we present a strategy to more reliably map transcriptome reads by taking advantage of the availability of both the genome reference sequence and transcript databases such as CCDS. We also present a novel Bayesian model for SNV discovery and genotyping based on quality scores.
  
  
  CONCLUSIONS
  Experimental results on RNA-Seq data generated from blood cell tissue of three Hapmap individuals show that our methods yield increased accuracy compared to several widely used methods. The open source code implementing our methods, released under the GNU General Public License, is available at http://dna.engr.uconn.edu/software/NGSTools/.
authors.affiliation: Department of Computer Science & Engineering, University of Connecticut, 371 Fairfield Rd, Unit 2155, Storrs, CT, 06269-2155, USA. jorge.duitamacastellanos@biw.vib-kuleuven.be.
authors.forename: Jorge
authors.initials: J
authors.lastname: Duitama
authors.forename: Pramod K
authors.initials: PK
authors.lastname: Srivastava
authors.forename: Ion I
authors.initials: II
authors.lastname: Măndoiu
mesh_terms: D001499:Bayes Theorem; D060005:Genotyping Techniques / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D017423:Sequence Analysis, RNA / Q000379:methods*; D012984:Software; D059467:Transcriptome