Improving alignment accuracy on homopolymer regions for semiconductor-based sequencing technologies

BMC Genomics

Research

Weixing Feng¹  Dingkai Xue¹  Sen Zhao¹  Fengfei Song¹  Ziwei Li¹  Duojiao Chen¹  Bo He¹  Yunlong Liu²  Yangyang Hao³  Yadong Wang⁴ 

[1] Automation College, Harbin Engineering University, Heilongjiang 150001, Harbin, People’s Republic of China;Automation College, Harbin Engineering University, Heilongjiang 150001, Harbin, People’s Republic of China;Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, 46202, Indianapolis, IN, USA;Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, 46202, Indianapolis, IN, USA;School of Computer Science and Technology, Harbin Institute of Technology, Heilongjiang 150001, Harbin, People’s Republic of China;

关键词: Homopolymer;    Ion Torrent/Proton;    Bayesian;    Alignment;   

DOI  :  10.1186/s12864-016-2894-9

来源: Springer

【 摘 要 】

BackgroundIon 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.ResultsIn 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.ConclusionsBesides 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.

【 授权许可】

CC BY   
© The Author(s). 2016