An improved encoding of genetic variation in a Burrows–Wheeler transform

In resequencing experiments, a high-throughput sequencer produces DNA-fragments (called reads) and each read is then mapped to the locus in a reference genome at which it fits best. Currently dominant read mappers are based on the Burrows-Wheeler transform (BWT). A read can be mapped correctly if it is similar enough to a substring of the reference genome. However, since the reference genome does not represent all known variations, read mapping tends to be biased towards the reference and mapping errors may thus occur. To cope with this problem, Huang et al. encoded single nucleotide polymorphisms (SNPs) in a BWT by the International Union of Pure and Applied Chemistry (IUPAC) nucleotide code. In a different approach, Maciuca et al. provided a 'natural encoding' of SNPs and other genetic variations in a BWT. However, their encoding resulted in a significantly increased alphabet size (the modified alphabet can have millions of new symbols, which usually implies a loss of efficiency). Moreover, the two approaches do not handle all known kinds of variation.