Aquila_stLFR: assembly based variant calling package for stLFR and hybrid assembly for linked-reads

Human diploid genome assembly enables identifying maternal and paternal genetic variations. Algorithms based on 10x linked-read sequencing have been developed for de novo assembly, variant calling and haplotyping. Another linked-read technology, single tube long fragment read (stLFR), has recently provided a low-cost single tube solution that can enable long fragment data. However, no existing software is available for human diploid assembly and variant calls. We develop Aquila stLFR to adapt to the key characteristics of stLFR. Aquila stLFR assembles near perfect diploid assembled contigs, and the assembly-based variant calling shows that Aquila stLFR detects large numbers of structural variants which were not easily spanned by Illumina short-reads. Furthermore, the hybrid assembly mode Aquila hybrid allows a hybrid assembly based on both stLFR and 10x linked-reads libraries, demonstrating that these two technologies can always be complementary to each other for assembly to improve contiguity and the variants detection, regardless of assembly quality of the library itself from single sequencing technology. The overlapped structural variants (SVs) from two independent sequencing data of the same individual, and the SVs from hybrid assemblies provide us a high-confidence profile to study them.