Fig. 1

Motivation and overview of diplotyping. a Gray sequences illustrate the haplotypes; the reads are shown in red and blue. The red reads originate from the upper haplotype, the blue ones from the lower. Genotyping each SNV individually would lead to the conclusion that all of them are heterozygous. Using the haplotype context reveals uncertainty about the genotype of the second SNV. b Clockwise starting top left: first, sequencing reads aligned to a reference genome are given as input; second, the read alignments are used to nominate candidate variants (red vertical bars), which are characterized by the differences to the reference genome; third, a hidden Markov model (HMM) is constructed where each candidate variant gives rise to one “row” of states, representing possible ways of assigning each read to one of the two haplotypes as well as possible genotypes (see the “Methods” section for details); forth, the HMM is used to perform diplotyping, i.e., we infer genotypes of each candidate variant as well as how the alleles are assigned to haplotypes