Genotype Calling and Haplotype Phasing from Next Generation Sequencing Data

Abstract

In this chapter, we will review current statistical andcomputational approaches for genotype calling and haplotypephasing from next generation data. We will focus on statisticalideas and ignore many practical bioinformatics issues such asimage processing for base calling, read mapping, sequencingerror rate recalibration, etc, each of which is a topic in itsown right. We will give derivations of commonly used approaches,emphasize their assumptions, and aim to unify them in anall-encompassing Bayesian framework. We will point outlimitations of single-site genotype likelihood methods thatdominate current practice and discuss strategies to usehaplotype informative reads.