Haplotype Threading: Accurate Polyploid Phasing from Long Reads

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

Abstract Resolving genomes at haplotype level is crucial for understanding the evolutionary history of polyploid species and for designing advanced breeding strategies. As a highly complex computational problem, polyploid phasing still presents considerable challenges, especially in regions of collapsing haplotypes. We present W hats H ap polyphase , a novel two-stage approach that addresses these challenges by (i) clustering reads using a position-dependent scoring function and (ii) threading the haplotypes through the clusters by dynamic programming. We demonstrate on a simulated data set that this results in accurate haplotypes with switch error rates that are around three times lower than those obtainable by the current state-of-the-art and even around seven times lower in regions of collapsing haplotypes. Using a real data set comprising long and short read tetraploid potato sequencing data we show that W hats H ap polyphase is able to phase the majority of the potato genes after error correction, which enables the assembly of local genomic regions of interest at haplotype level. Our algorithm is implemented as part of the widely used open source tool WhatsHap and ready to be included in production settings.

Authors 9

1. Sven D. Schrinner

   Heinrich Heine University Düsseldorf

   Affiliation as printed

   Algorithmic Bioinformatics, Heinrich Heine University Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany

   Algorithmic Bioinformatics, Heinrich Heine University Düsseldorf, Universitätsstr. , 40225 Düsseldorf, Germany

2. Rebecca Serra Mari

   Saarland University

   Affiliation as printed

   Center for Bioinformatics, Saarland University, 66123 Saarbrücken, Germany

   Graduate School of Computer Science, 66123 Saarbrücken, Germany

   Center for Bioinformatics, Saarland University, 6613 Saarbrücken, Germany

   Graduate School of Computer Science, 6612 Saarbrücken, Germany

3. Jana Ebler

   Saarland University · Max Planck Institute for Informatics

   Affiliation as printed

   Center for Bioinformatics, Saarland University, 66123 Saarbrücken, Germany

   Graduate School of Computer Science, 66123 Saarbrücken, Germany

   Max Planck Institute for Informatics, 66123 Saarbrücken, Germany

   Center for Bioinformatics, Saarland University, 6613 Saarbrücken, Germany

   Graduate School of Computer Science, 6612 Saarbrücken, Germany

   Max Planck Institute for Informatics, 123 Saarbrücken, Germany

4. Mikko Rautiainen

   Max Planck Institute for Informatics

   Affiliation as printed

   Max Planck Institute for Informatics, 66123 Saarbrücken, Germany

   Max Planck Institute for Informatics, 123 Saarbrücken, Germany

5. Lancelot Seillier Aachen Institute for Biology I

   RWTH Aachen University

   Affiliation as printed

   Institute for Biology I, RWTH Aachen, Worringer Weg 3, 52078 Aachen, Germany

   Institute for Biology I, RWTH Aachen, Worringer Weg 3, 2078 Aachen, Germany

6. Julia J. Reimer Aachen Institute for Biology I

   RWTH Aachen University

   Affiliation as printed

   Institute for Biology I, RWTH Aachen, Worringer Weg 3, 52078 Aachen, Germany

   Institute for Biology I, RWTH Aachen, Worringer Weg 3, 2078 Aachen, Germany

7. Björn Usadel Aachen Institute for Biology I

   RWTH Aachen University · Forschungszentrum Jülich · Heinrich Heine University Düsseldorf · Cluster of Excellence on Plant Sciences

   Affiliation as printed

   Cluster of Excellence on Plant Sciences (CEPLAS), Heinrich Heine University Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany

   Forschungszentrum Jülich IBG-4, Wilhelm- Johnen-Str., 52428 Jülich, Germany

   Institute for Biology I, RWTH Aachen, Worringer Weg 3, 52078 Aachen, Germany

   Forschungszentrum Jülich IBG-, Wilhelm- Johnen-Str., 5228 Jülich, Germany

   Institute for Biology I, RWTH Aachen, Worringer Weg 3, 2078 Aachen, Germany

8. Tobias Marschall

   Saarland University · Max Planck Institute for Informatics

   Affiliation as printed

   Center for Bioinformatics, Saarland University, 66123 Saarbrücken, Germany

   Max Planck Institute for Informatics, 66123 Saarbrücken, Germany

   Center for Bioinformatics, Saarland University, 6613 Saarbrücken, Germany

   Max Planck Institute for Informatics, 123 Saarbrücken, Germany

9. Gunnar W. Klau corresponding

   Heinrich Heine University Düsseldorf · Cluster of Excellence on Plant Sciences

   Affiliation as printed

   Algorithmic Bioinformatics, Heinrich Heine University Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany

   Cluster of Excellence on Plant Sciences (CEPLAS), Heinrich Heine University Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany

   Algorithmic Bioinformatics, Heinrich Heine University Düsseldorf, Universitätsstr. , 40225 Düsseldorf, Germany