A Bayesian approach to haplotype-aware de novo genome assembly for polyploid organisms

A Bayesian approach to haplotype-aware de novo genome assembly for polyploid organisms

van Dijk, Lucas (TU Delft Electrical Engineering, Mathematics and Computer Science)

Abeel, T.E.P.M.F. (mentor)

Delft University of Technology

Computer Science | Bioinformatics

2017-08-29

Capturing all genetic variation within a polyploid organism is a challenge. Most current de novo assemblers have no notion of the concept “ploidy”. Consequently, when assembling the genome of diploid or higher ploidy organisms, the assembler mixes reads coming from either chromosome copy and builds a single DNA sequence representing an arbitrary composition of a set of homologous chromosomes. This hampers any downstream analysis, such as allele specific expression analysis, gene association studies or population genetics. Current haplotype assembly methods focus on phasing single nucleotide variants (SNVs), and are limited in their ability to deal with larger and structural variants.

The third generation sequencing platforms, like the PacBio RS II or the Oxford Nanopore, make long read sequencing affordable. In this work we explore a novel method using long reads and an assembly graph to phase haplotypes. We introduce PHASM: a prototype de novo genome assembler that outputs separate DNA sequences for each haplotype. We show that phasing using an assembly graph has potential, but that approximate alignments between reads introduces caveats that make this problem difficult.

Genome Assembly
Haplotype Phasing
bioinformatics

http://resolver.tudelft.nl/uuid:4c7ce6eb-dd69-49e9-bb68-12d7efb5afdf

Student theses

master thesis

© 2017 Lucas van Dijk