title: BAsE-Seq: a method for obtaining long viral  haplotypes from short sequence reads.
abstract: We present a method for obtaining long haplotypes, of over 3 kb in length, using a short-read sequencer, Barcode-directed Assembly for Extra-long Sequences (BAsE-Seq). BAsE-Seq relies on transposing a template-specific barcode onto random segments of the template molecule and assembling the barcoded short reads into complete haplotypes. We applied BAsE-Seq on mixed clones of hepatitis B virus and accurately identified haplotypes occurring at frequencies greater than or equal to 0.4%, with >99.9% specificity. Applying BAsE-Seq to a clinical sample, we obtained over 9,000 viral haplotypes, which provided an unprecedented view of hepatitis B virus population structure during chronic infection. BAsE-Seq is readily applicable for monitoring quasispecies evolution in viral diseases.
authors.forename: Lewis Z
authors.initials: LZ
authors.lastname: Hong
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Hong
authors.forename: Han Teng
authors.initials: HT
authors.lastname: Wong
authors.forename: Pauline P K
authors.initials: PP
authors.lastname: Aw
authors.forename: Yan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Andreas
authors.initials: A
authors.lastname: Wilm
authors.forename: Paola F
authors.initials: PF
authors.lastname: de Sessions
authors.forename: Seng Gee
authors.initials: SG
authors.lastname: Lim
authors.forename: Niranjan
authors.initials: N
authors.lastname: Nagarajan
authors.forename: Martin L
authors.initials: ML
authors.lastname: Hibberd
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Quake
authors.forename: William F
authors.initials: WF
authors.lastname: Burkholder
mesh_terms: D000465:Algorithms; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics*; D006509:Hepatitis B / Q000235:genetics / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software