A Hierarchical Dirichlet Process Mixture Model for Haplotype Reconstruction from Multi-Population Data

Uncovering the haplotypes of single nucleotide polymorphisms is essential for many biological and medical applications. While it is uncommon for the genotype data to be pooled from multiple ethnically distinct populations, few existing programs have explicitly leverage the individual ethnic information for haplotype inference. In this paper, we present a new haplotype inference program, Haploi, which makes use of such information and is readily applicable to genotype sequences with thousands of SNPs from heterogeneous populations, with competent and sometimes superior speed and accuracy comparing to the state-of-the-art programs. Underlying Haploi is a new haplotype distribution model based on a nonparametric Bayesian formalism known as the hierarchical Dirichlet process, which represents a tractable surrogate to the coalescent process. The proposed model is exchangeable, unbounded, and capable of coupling demographic information of different populations. It offers a well-founded statistical framework for posterior inference of individual haplotypes, the size and configuration of haplotype ancestor pools, and other parameters of interest given genotype data.