UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

Scalable methods for improving genome assemblies Nikolić, Vladimir


De novo genome assembly is cornerstone to modern genomics studies. It is also a useful method for studying genomes with high variation, such as cancer genomes, as it is not biased by a reference. De novo short-read assemblers commonly use de Bruijn graphs, where nodes are sequences of equal length k, also known as k-mers. Edges in this graph are established between nodes that overlap by k - 1 bases, followed by merging nodes along unambiguous walks in the graph. The selection of k is influenced by a few factors, and its fine tuning results in a trade-off between graph connectivity and sequence contiguity. Ideally, multiple k sizes should be used, so lower values can provide good connectivity in lesser covered regions and higher values can increase contiguity in well-covered regions. However, this approach has only been explored with small genomes, without addressing scalability issues with larger ones. Here we present RResolver, a scalable algorithm that takes a short-read de Bruijn graph assembly with a starting k as input and uses a k value closer to that of the read length to resolve repeats. RResolver builds a Bloom filter of sequencing reads which it uses to evaluate the assembly graph path support at branching points and removes the paths with insufficient support. RResolver runs efficiently, taking 3% of a typical ABySS human assembly pipeline run time on average with 48 threads and 40GB memory. Compared to a baseline assembly, RResolver improves scaffold contiguity (NGA50) by up to 16% and reduces misassemblies by up to 7%. RResolver adds a missing component to scalable de Bruijn graph genome assembly. By improving the initial and fundamental graph traversal outcome, all downstream ABySS algorithms greatly benefit by working with a more accurate and less complex representation of the genome.

Item Media

Item Citations and Data


Attribution-ShareAlike 4.0 International