Simple adjustment of the sequence weight algorithm remarkably enhances PSI-BLAST performance

• Published in: BMC bioinformatics Vol. 18; no. 1; p. 288
• Main Authors: Oda, Toshiyuki, Lim, Kyungtaek, Tomii, Kentaro
• Format: Journal Article
• Language: English
• Published: England BioMed Central 02-06-2017; BMC
• Subjects: Algorithms; Amino Acid Sequence; Area Under Curve; Databases, Factual; Position-Specific Scoring Matrices; Position-specific scoring matrix; Proteins - chemistry; PSI-BLAST; ROC Curve; Sequence Alignment - methods; Sequence similarity search; Sequence weighting; Software; Sequence weighting; Sequence similarity search; Position-specific scoring matrix; PSI-BLAST
• ISSN: 1471-2105; 1471-2105
• DOI: 10.1186/s12859-017-1686-9

PSI-BLAST, an extremely popular tool for sequence similarity search, features the utilization of Position-Specific Scoring Matrix (PSSM) constructed from a multiple sequence alignment (MSA). PSSM allows the detection of more distant homologs than a general amino acid substitution matrix does. An accurate estimation of the weights for sequences in an MSA is crucially important for PSSM construction. PSI-BLAST divides a given MSA into multiple blocks, for which sequence weights are calculated. When the block width becomes very narrow, the sequence weight calculation can be odd.
We demonstrate that PSI-BLAST indeed generates a significant fraction of blocks having width less than 5, thereby degrading the PSI-BLAST performance. We revised the code of PSI-BLAST to prevent the blocks from being narrower than a given minimum block width (MBW). We designate the modified application of PSI-BLAST as PSI-BLASTexB. When MBW is 25, PSI-BLASTexB notably outperforms PSI-BLAST consistently for three independent benchmark sets. The performance boost is even more drastic when an MSA, instead of a sequence, is used as a query.
Our results demonstrate that the generation of narrow-width blocks during the sequence weight calculation is a critically important factor that restricts the PSI-BLAST search performance. By preventing narrow blocks, PSI-BLASTexB upgrades the PSI-BLAST performance remarkably. Binaries and source codes of PSI-BLASTexB (MBW = 25) are available at https://github.com/kyungtaekLIM/PSI-BLASTexB .