BAsE-Seq: a method for obtaining long viral haplotypes from short sequence reads.
Hong, Lewis Z;
Hong, Shuzhen;
Wong, Han Teng;
Aw, Pauline PK;
Cheng, Yan;
Wilm, Andreas;
de Sessions, Paola F;
Lim, Seng Gee;
Nagarajan, Niranjan;
Hibberd, Martin L;
+2 more...Quake, Stephen R;
Burkholder, William F;
(2014)
BAsE-Seq: a method for obtaining long viral haplotypes from short sequence reads.
Genome Biol, 15 (11).
517-.
ISSN 1474-760X
DOI: https://doi.org/10.1186/PREACCEPT-6768001251451949
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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.