Hap-Browser: a web application for gene-level haplotype visualization and marker design

Abstract

Haplotype structure of a candidate gene provides crop geneticists with a wealth of information, including the interpretation of GWAS peaks, the identification of suitable parents for cross-breeding to achieve allelic diversity, and the placement of a diagnostic marker. Resequencing efforts, such as the 3,010 Rice Genomes panel, have now rendered hundreds of accessions accessible at any locus. Turning that resource into a usable haplotype summary, however, is still a fragmented job. Alignment browsers and variant databases each cover part of the task, but the read counts supporting a call and the panel-wide pattern of alleles are presented in separate views, and neither leads on to haplotype classification or marker design. Consequently, researchers are required to transition between three or four tools manually. Hap-Browser consolidates these steps into a single interface. It reads precomputed pileups and draws a whole panel as a sample-by-position matrix, then groups accessions by haplotype over any set of positions the user selects and reports the amino-acid changes that follow. From the same view, it designs allele-specific KASP and InDel primers, checking every variant within the primer-binding regions across the panel so that primers likely to fail on some accessions are flagged before they are ordered. Query sequences can be assigned to known haplotypes by BLAST. Because the pileups are precomputed, a 200-accession panel is fetched and cached once when a gene is first opened, after which reclassifying haplotypes and recomputing the view are effectively instantaneous. The demonstration set covers 23 rice heading-date genes and Sub1A across 200 accessions from the IRRI panel; adding a gene means editing a single tab-separated line and rerunning a Snakemake pipeline, and nothing in the design ties it to rice in its inputs, although the demonstration presented here is confined to a single species. By keeping panel-wide haplotype inspection and variant-aware marker design within one session, Hap-Browser removes most of the manual hand-off this workflow used to require. The source code, pipeline, and demonstration data are openly available for other groups to use and extend.