title: SeqHBase: a big data toolset for family based sequencing data analysis.
abstract: BACKGROUND
  Whole-genome sequencing (WGS) and whole-exome sequencing (WES) technologies are increasingly used to identify disease-contributing mutations in human genomic studies. It can be a significant challenge to process such data, especially when a large family or cohort is sequenced. Our objective was to develop a big data toolset to efficiently manipulate genome-wide variants, functional annotations and coverage, together with conducting family based sequencing data analysis.
  
  
  METHODS
  Hadoop is a framework for reliable, scalable, distributed processing of large data sets using MapReduce programming models. Based on Hadoop and HBase, we developed SeqHBase, a big data-based toolset for analysing family based sequencing data to detect de novo, inherited homozygous, or compound heterozygous mutations that may contribute to disease manifestations. SeqHBase takes as input BAM files (for coverage at every site), variant call format (VCF) files (for variant calls) and functional annotations (for variant prioritisation).
  
  
  RESULTS
  We applied SeqHBase to a 5-member nuclear family and a 10-member 3-generation family with WGS data, as well as a 4-member nuclear family with WES data. Analysis times were almost linearly scalable with number of data nodes. With 20 data nodes, SeqHBase took about 5 secs to analyse WES familial data and approximately 1 min to analyse WGS familial data.
  
  
  CONCLUSIONS
  These results demonstrate SeqHBase's high efficiency and scalability, which is necessary as WGS and WES are rapidly becoming standard methods to study the genetics of familial disorders.
authors.affiliation: Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, Wisconsin, USA Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, Wisconsin, USA Department of Computation and Informatics in Biology and Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Min
authors.initials: M
authors.lastname: He
authors.affiliation: Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, Wisconsin, USA.
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Person
authors.affiliation: Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, Wisconsin, USA Department of Computation and Informatics in Biology and Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Hebbring
authors.affiliation: College of Science and Engineering, University of Minnesota-Twin Cities, Minnesota, Minnesota, USA.
authors.forename: Ethan
authors.initials: E
authors.lastname: Heinzen
authors.affiliation: Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, Wisconsin, USA.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, Wisconsin, USA Department of Computation and Informatics in Biology and Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Schrodi
authors.affiliation: Department of Medical Genetics Services, Marshfield Clinic, Marshfield, Wisconsin, USA.
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: McPherson
authors.affiliation: The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Lin
authors.affiliation: Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, Wisconsin, USA.
authors.forename: Peggy L
authors.initials: PL
authors.lastname: Peissig
authors.affiliation: Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, Wisconsin, USA Department of Computation and Informatics in Biology and Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Murray H
authors.initials: MH
authors.lastname: Brilliant
authors.affiliation: Cold Spring Harbor Laboratory, Stanley Institute for Cognitive Genomics, Cold Spring Harbor, New York, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: O'Rawe
authors.affiliation: Utah Foundation for Biomedical Research, Provo, Utah, USA.
authors.forename: Reid J
authors.initials: RJ
authors.lastname: Robison
authors.affiliation: Cold Spring Harbor Laboratory, Stanley Institute for Cognitive Genomics, Cold Spring Harbor, New York, USA Utah Foundation for Biomedical Research, Provo, Utah, USA.
authors.forename: Gholson J
authors.initials: GJ
authors.lastname: Lyon
authors.affiliation: Utah Foundation for Biomedical Research, Provo, Utah, USA Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California, USA Department of Psychiatry, University of Southern California, Los Angeles, California, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
mesh_terms: D066264:Datasets as Topic; D059472:Exome; D015894:Genome, Human; D023281:Genomics / Q000379:methods*; D006801:Humans; D009154:Mutation; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software
keywords: big data; de novo mutations; inherited homozygous or compound heterozygous mutations; whole-exome sequencing; whole-genome sequencing