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Practical probabilistic and graphical formulations of long-read polyploid haplotype phasing


Resolving haplotypes in polyploid genomes using phase information from sequencing reads is an important and challenging problem. We introduce two new mathematical formulations of polyploid haplotype phasing: (1) the min-sum max tree partition (MSMTP) problem, which is a more flexible graphical metric compared to the standard minimum error correction (MEC) model in the polyploid setting, and (2) the uniform probabilistic error minimization (UPEM) model, which is a probabilistic analogue of the MEC model. We incorporate both formulations into a long-read based polyploid haplotype phasing method called flopp. We show that flopp compares favorably to state-of-the-art algorithms—up to 30 times faster with 2 times fewer switch errors on 6x ploidy simulated data.

Authors: Jim Shaw, Yun William Yu

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