Deep mutational scanning by nicking, shotgun sequencing and nf-core/deepmutscan
nf-core/deepmutscan is a workflow designed for the analysis of deep mutational scanning (DMS) data. DMS enables researchers to experimentally measure the fitness effects of thousands of genes or gene variants simultaneously, helping to classify disease causing mutants in human and animal populations, to learn the fundamental rules of protein architecture, small-molecule binding, mRNA splicing, viral evolution and many other quantifiable phenotypes. While DNA synthesis and sequencing technologies have advanced substantially, long open reading frame (ORF) targets still present a major challenge for DMS studies. Shotgun DNA sequencing can be used to greatly speed up the inference of long ORF mutant fitness landscapes, theoretically at no expense in accuracy. We have designed the nf-core/deepmutscan pipeline to unlock the power of shotgun sequencing based DMS studies on long ORFs, to simplify and standardise the complex bioinformatics steps involved in data processing of such experiments – from read alignment to QC reporting and fitness landscape inferences.