Mapping short reads to a reference genome is an essential step in many next-generation sequencing (NGS) analysis. In plants with large genomes, a large fraction of the reads can align to multiple locations of the genome with equally good alignment scores. How to map these ambiguous reads to the genome is a challenging problem with big impacts in the downstream analysis. Traditionally, the default method is to assign an ambiguous read randomly to one of the many potential locations. In this study, we explore an enrichment method that assigns an ambiguous read to the location that has produced the most reads among all the potential locations. Our results show that the enrichment method produced better results than the default random method in the discovery of single nucleotide polymorphisms (SNPs). Not only did it produce more SNP markers, but it also produced markers with better quality, which was demonstrated by higher trait-marker correlation in genome-wide association studies (GWAS).
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