Local weighting schemes for protein multiple sequence alignment

This paper describes three weighting schemes for improving the accuracy of progressive multiple sequence alignment methods: (1) global profile pre-processing, to capture for each sequence information about other sequences in a profile before the actual multiple alignment takes place; (2) local pre-processing; which incorporates a new protocol to only use non-overlapping local sequence regions to construct the pre-processed profiles; and (3) local–global alignment, a weighting scheme based on the double dynamic programming (DDP) technique to softly bias global alignment to local sequence motifs. The first two schemes allow the compilation of residue-specific multiple alignment reliability indices, which can be used in an iterative fashion. The schemes have been implemented with associated iterative modes in the PRALINE multiple sequence alignment method, and have been evaluated using the BAliBASE benchmark alignment database. These tests indicate that PRALINE is a toolbox able to build alignments with very high quality. We found that local profile pre-processing raises the alignment quality by 5.5% compared to PRALINE alignments generated under default conditions. Iteration enhances the quality by a further percentage point. The implications of multiple alignment scoring functions and iteration in relation to alignment quality and benchmarking are discussed.