title: Improving alignment accuracy on homopolymer regions for semiconductor-based sequencing technologies.
abstract: Ion Torrent and Ion Proton are semiconductor-based sequencing technologies that feature rapid sequencing speed and low upfront and operating costs, thanks to the avoidance of modified nucleotides and optical measurements. Despite of these advantages, however, Ion semiconductor sequencing technologies suffer much reduced sequencing accuracy at the genomic loci with homopolymer repeats of the same nucleotide. Such limitation significantly reduces its efficiency for the biological applications aiming at accurately identifying various genetic variants.
  
  
  
  In this study, we propose a Bayesian inference-based method that takes the advantage of the signal distributions of the electrical voltages that are measured for all the homopolymers of a fixed length. By cross-referencing the length of homopolymers in the reference genome and the voltage signal distribution derived from the experiment, the proposed integrated model significantly improves the alignment accuracy around the homopolymer regions.
  
  
  
  Besides improving alignment accuracy on homopolymer regions for semiconductor-based sequencing technologies with the proposed model, similar strategies can also be used on other high-throughput sequencing technologies that share similar limitations.
authors.affiliation: Automation College, Harbin Engineering University, Harbin, Heilongjiang 150001, People's Republic of China.
authors.forename: Weixing
authors.initials: W
authors.lastname: Feng
authors.affiliation: Automation College, Harbin Engineering University, Harbin, Heilongjiang 150001, People's Republic of China.
authors.forename: Sen
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Automation College, Harbin Engineering University, Harbin, Heilongjiang 150001, People's Republic of China.
authors.forename: Dingkai
authors.initials: D
authors.lastname: Xue
authors.affiliation: Automation College, Harbin Engineering University, Harbin, Heilongjiang 150001, People's Republic of China.
authors.forename: Fengfei
authors.initials: F
authors.lastname: Song
authors.affiliation: Automation College, Harbin Engineering University, Harbin, Heilongjiang 150001, People's Republic of China.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Li
authors.affiliation: Automation College, Harbin Engineering University, Harbin, Heilongjiang 150001, People's Republic of China.
authors.forename: Duojiao
authors.initials: D
authors.lastname: Chen
authors.affiliation: Automation College, Harbin Engineering University, Harbin, Heilongjiang 150001, People's Republic of China. bohe@hrbeu.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: He
authors.affiliation: Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Hao
authors.affiliation: School of Computer Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang 150001, People's Republic of China.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Automation College, Harbin Engineering University, Harbin, Heilongjiang 150001, People's Republic of China. yunliu@iupui.edu.|Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. yunliu@iupui.edu.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Liu
mesh_terms: D001499:Bayes Theorem; D014644:Genetic Variation; D016678:Genome; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D016415:Sequence Alignment / Q000379:methods*; D017422:Sequence Analysis, DNA / Q000379:methods*; D020080:Tandem Repeat Sequences / Q000235:genetics*
keywords: Alignment; Bayesian; Homopolymer; Ion Torrent/Proton