title: Deep sequencing of a genetically heterogeneous sample: local haplotype reconstruction and read error correction.
abstract: We present a computational method for analyzing deep sequencing data obtained from a genetically diverse sample. The set of reads obtained from a deep sequencing experiment represents a statistical sample of the underlying population. We develop a generative probabilistic model for assigning observed reads to unobserved haplotypes in the presence of sequencing errors. This clustering problem is solved in a Bayesian fashion using the Dirichlet process mixture to define a prior distribution on the unknown number of haplotypes in the mixture. We devise a Gibbs sampler for sampling from the joint posterior distribution of haplotype sequences, assignment of reads to haplotypes, and error rate of the sequencing process, to obtain estimates of the local haplotype structure of the population. The method is evaluated on simulated data and on experimental deep sequencing data obtained from HIV samples.
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland. osvaldo.zagordi@bsse.ethz.ch
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Zagordi
authors.forename: Lukas
authors.initials: L
authors.lastname: Geyrhofer
authors.forename: Volker
authors.initials: V
authors.lastname: Roth
authors.forename: Niko
authors.initials: N
authors.lastname: Beerenwinkel
mesh_terms: D015658:HIV Infections / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D012107:Research Design; D017422:Sequence Analysis, DNA / Q000379:methods*