Hybrid-hybrid correction of errors in long reads with HERO

Although generally superior, hybrid approaches for correcting errors in third-generation sequencing (TGS) reads, using next-generation sequencing (NGS) reads, mistake haplotype-specific variants for errors in polyploid and mixed samples. We suggest HERO, as the first “hybrid-hybrid” approach, to make use of both de Bruijn graphs and overlap graphs for optimal catering to the particular strengths of NGS and TGS reads. Extensive benchmarking experiments demonstrate that HERO improves indel and mismatch error rates by on average 65% (27[Formula: see text] 95%) and 20% (4[Formula: see text] 61%). Using HERO prior to genome assembly significantly improves the assemblies in the majority of the relevant categories. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-023-03112-7.