title: Robust and rapid algorithms facilitate large-scale whole genome sequencing downstream analysis in an integrative framework.
abstract: Whole genome sequencing (WGS) is a promising strategy to unravel variants or genes responsible for human diseases and traits. However, there is a lack of robust platforms for a comprehensive downstream analysis. In the present study, we first proposed three novel algorithms, sequence gap-filled gene feature annotation, bit-block encoded genotypes and sectional fast access to text lines to address three fundamental problems. The three algorithms then formed the infrastructure of a robust parallel computing framework, KGGSeq, for integrating downstream analysis functions for whole genome sequencing data. KGGSeq has been equipped with a comprehensive set of analysis functions for quality control, filtration, annotation, pathogenic prediction and statistical tests. In the tests with whole genome sequencing data from 1000 Genomes Project, KGGSeq annotated several thousand more reliable non-synonymous variants than other widely used tools (e.g. ANNOVAR and SNPEff). It took only around half an hour on a small server with 10 CPUs to access genotypes of ∼60 million variants of 2504 subjects, while a popular alternative tool required around one day. KGGSeq's bit-block genotype format used 1.5% or less space to flexibly represent phased or unphased genotypes with multiple alleles and achieved a speed of over 1000 times faster to calculate genotypic correlation.
authors.affiliation: Department of Medical Genetics, Center for Genome Research, Center for Precision Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.|The Centre for Genomic Sciences, the University of Hong Kong, Pokfulam, Hong Kong.|Department of Psychiatry, the University of Hong Kong, Pokfulam, Hong Kong.|State Key Laboratory for Cognitive and Brain Sciences, the University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Miaoxin
authors.initials: M
authors.lastname: Li
authors.affiliation: School of Biomedical Sciences, the University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
authors.affiliation: The Centre for Genomic Sciences, the University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Mulin Jun
authors.initials: MJ
authors.lastname: Li
authors.affiliation: Department of Psychiatry, the University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Pan
authors.affiliation: Department of Psychiatry, the University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Jacob Shujui
authors.initials: JS
authors.lastname: Hsu
authors.affiliation: Division of Biostatistics and Bioinformatics, Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA 17033, USA.|Institute for Personalized Medicine, Penn State College of Medicine, Hershey, PA 17033, USA.
authors.forename: Dajiang J
authors.initials: DJ
authors.lastname: Liu
authors.affiliation: Quantitative Biomedical Research Center, Department of Clinical Science, Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhan
authors.affiliation: The Centre for Genomic Sciences, the University of Hong Kong, Pokfulam, Hong Kong.|Department of Health Sciences Research and Center for Individualized Medicine, Mayo Clinic, Scottsdale, AZ 85259, USA.|Department of Biomedical Informatics, Arizona State University, Scottsdale, AZ 85259, USA.
authors.forename: Junwen
authors.initials: J
authors.lastname: Wang
authors.affiliation: The Centre for Genomic Sciences, the University of Hong Kong, Pokfulam, Hong Kong.|School of Biomedical Sciences, the University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Youqiang
authors.initials: Y
authors.lastname: Song
authors.affiliation: The Centre for Genomic Sciences, the University of Hong Kong, Pokfulam, Hong Kong.|Department of Psychiatry, the University of Hong Kong, Pokfulam, Hong Kong.|State Key Laboratory for Cognitive and Brain Sciences, the University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Pak Chung
authors.initials: PC
authors.lastname: Sham
mesh_terms: D000465:Algorithms; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D017422:Sequence Analysis, DNA / Q000379:methods*