Current short read mapping programs are based on the reasonable premise that most sequencing errors occur near the 3() end of the read. These programs map reads with either a small number of mismatches in the entire read, or a small number of mismatches in the segment remaining after trimming bases from the 3() end or a single base from the 5() end. Though multiple sequencing errors most likely occur near the 3() end of the reads, they can still occur at the 5() end of the reads. Trimming from the 3() end will not be able to map these reads. We have developed a program, Maximum Oligonucleotide Mapping (MOM), based on the concept of query matching that is designed to capture a maximal length match within the short read satisfying the user defined error parameters. This query matching approach thus accommodates multiple sequencing errors at both ends. We demonstrate that this technique achieves greater sensitivity and a higher percentage of uniquely mapped reads when compared to existing programs such as SOAP, MAQ and SHRiMP. Software and Test Data