Improved Sensitivity of Nucleic Acid Database Searches Using Application-Specific Scoring Matrices

Scoring matrices for nucleic acid sequence comparison that are based on models appropriate to the analysis of molecular sequencing errors or biological mutation processes are presented. In mammalian genomes, transition mutations occur significantly more frequently than transversions, and the optimal scoring of sequence alignments based on this substitution model differs from that derived assuming a uniform mutation model. The information from sequence alignments potentially available using an optimal scoring system is compared with that obtained using the BLASTN default scoring. A modified BLAST database search tool allows these, or other explicitly specified scoring matrices, to be utilized in computationally efficient queries of nucleic acid databases with nucleic acid query sequences. Results of searches performed using BLASTN's default score matrix are compared with those using scores based on a mutational model in which transitions are more prevalent than transversions.