Fast and accurate alignment of barcoded reads

Abstract

Over the last few years, we have seen the emergence of several so-called "third-generation" sequencing platforms, which improve on standard short-read sequencing that has thus far been at the center of next-generation sequencing. While technologies developed by Pacific Biosciences and Oxford Nanopore accomplish this goal by producing physically longer reads, several other technologies take an alternate route by instead producing "barcoded reads", including 10x Genomics' Chromium platform and Illumina's TruSeq Synthetic Long-Read platform. With barcoded reads, long-range information is captured by the barcodes, which identify source DNA fragments. As with all sequencing data, alignment of barcoded reads is the first step in nearly all analyses, and therefore plays a central role. Here, we design and validate improved alignment algorithms for barcoded sequencing data, which enable improved downstream analyses like phasing and genotyping, and additionally uncover variants in regions containing nearby homologous elements that go undetected by other methods.