ntEdit: scalable genome sequence polishing

Motivation: In the modern genomics era, genome sequence assemblies are routine practice. However, depending on the methodology, resulting drafts may contain considerable base errors. Although utilities exist for genome base polishing, they work best with high read coverage and do not scale well. We developed ntEdit, a Bloom filter-based genome sequence editing utility that scales to large mammalian and conifer genomes. Results: We first tested ntEdit and the state-of-the-art assembly improvement tools GATK, Pilon and Racon on controlled Escherichia coli and Caenorhabditis elegans sequence data. Generally, ntEdit performs well at low sequence depths (<20x), fixing the majority (>97%) of base substitutions and indels, and its performance is largely constant with increased coverage. In all experiments conducted using a single CPU, the ntEdit pipeline executed in <14s and <3m, on average, on E.coli and C.elegans, respectively. We performed similar benchmarks on a sub-20x coverage human genome sequence dataset, inspecting accuracy and resource usage in editing chromosomes 1 and 21, and whole genome. ntEdit scaled linearly, executing in 30-40m on those sequences. We show how ntEdit ran in <2 h 20 m to improve upon long and linked read human genome assemblies of NA12878, using high-coverage (54x) Illumina sequence data from the same individual, fixing frame shifts in coding sequences. We also generated 17-fold coverage spruce sequence data from haploid sequence sources (seed megagametophyte), and used it to edit our pseudo haploid assemblies of the 20 Gb interior and white spruce genomes in <4 and <5h, respectively, making roughly 50M edits at a (substitution+indel) rate of 0.0024.