npInv: accurate detection and genotyping of inversions mediated by non-allelic homologous recombination using long read sub-alignment

Abstract

Detection of genomic inversions remains challenging. Many existing methods primarily target inversions with a non repetitive breakpoint, leaving inverted repeat (IR) mediated non-allelic homologous recombination (NAHR) inversions largely unexplored. We present npInv, a novel tool specifically for detecting and genotyping NAHR inversion using long read sub-alignment of long read sequencing data. We use npInv to generate a whole-genome inversion map for NA12878 consisting of 30 NAHR inversions (of which 15 are novel), including all previously known NAHR mediated inversions in NA12878 with flanking IR less than 7kb. Our genotyping accuracy on this dataset was 94%. We used PCR to confirm presence of two of these novel NAHR inversions. We show that there is a near linear relationship between the length of flanking IR and the size of the NAHR inversion.