Aquila_stLFR: diploid genome assembly basedstructural variant calling package for stLFRlinked-read

Abstract

MotivationIdentifying structural variants (SVs) is of critical importance in health and disease, however, detecting them remains a scientific and computing challenge. Several linked-read sequencing technologies, including 10X linked-read, TELL-Seq, and single tube long fragment read (stLFR), have been recently developed as cost-effective approaches to reconstruct multi-megabase haplotypes (phase blocks) from sequence data of a single sample. These technologies provide an optimal sequencing platform to characterize SVs, though few computational algorithms can utilize them. Thus, we developed Aquila_stLFR, an approach that resolves SVs through haplotype-based assembly of stLFR linked-reads. ResultsAquila_stLFR first partitions LFRs into two haplotype-specific blocks, by taking advantage of the potential phasing ability of the linked-read itself. Each haplotype is then assembled independently, to achieve a complete diploid assembly to finally reconstruct the genome-wide SVs. We benchmarked Aquila_stLFR on a well-studied sample, NA24385, and showed Aquila_stLFR can detect medium to large size (50bp - 10kb) deletions with a high sensitivity and insertions with a high specificity. AvailabilitySource code and documentation are available on https://github.com/maiziex/Aquila_stLFR. Contactmaizie.zhou@vanderbilt.edu Supplementary informationSupplementary data are available at Bioinformatics online.