Scalable multiple whole-genome alignment and locally collinear block construction with SibeliaZ

Ilia Minkin,Paul Medvedev

doi:10.1038/s41467-020-19777-8

Abstract

Multiple whole-genome alignment is a challenging problem in bioinformatics. Despite many successes, current methods are not able to keep up with the growing number, length, and complexity of assembled genomes, especially when computational resources are limited. Approaches based on compacted de Bruijn graphs to identify and extend anchors into locally collinear blocks have potential for scalability, but current methods do not scale to mammalian genomes. We present an algorithm, SibeliaZ-LCB, for identifying collinear blocks in closely related genomes based on analysis of the de Bruijn graph. We further incorporate this into a multiple whole-genome alignment pipeline called SibeliaZ. SibeliaZ shows run-time improvements over other methods while maintaining accuracy. On sixteen recently-assembled strains of mice, SibeliaZ runs in under 16 hours on a single machine, while other tools did not run to completion for eight mice within a week. SibeliaZ makes a significant step towards improving scalability of multiple whole-genome alignment and collinear block reconstruction algorithms on a single machine.

Highlights

Multiple whole-genome alignment is a challenging problem in bioinformatics
SibeliaZ-LCB takes as input a de Bruijn graph built on a collection of assembled genomes
We presented a whole-genome alignment pipeline SibeliaZ based on an algorithm for identifying locally collinear blocks

Summary

Introduction

Multiple whole-genome alignment is a challenging problem in bioinformatics. Despite many successes, current methods are not able to keep up with the growing number, length, and complexity of assembled genomes, especially when computational resources are limited. Approaches based on compacted de Bruijn graphs to identify and extend anchors into locally collinear blocks have potential for scalability, but current methods do not scale to mammalian genomes. SibeliaZ-LCB, for identifying collinear blocks in closely related genomes based on analysis of the de Bruijn graph. All of the methods applicable to datasets consisting of multiple genomes are heuristic since the exact algorithms depend exponentially on the number of genomes Such strategies are generally better at scaling to handle repeats and multiple genomes since they do not rely on the computationally expensive pairwise alignment. A promising strategy to find collinear blocks is based on the compacted de Bruijn graph[21,22,23] widely used in genome assembly Though these approaches do not work well for divergent genomes, they remain fairly accurate for closely related genomes. We believe the de Bruijn graph approach holds the most potential for enabling scalable multiple whole-genome alignments of closely related genomes

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Results

Conclusion