SMI-BLAST: a novel supervised search framework based on PSI-BLAST for protein remote homology detection.

MOTIVATION As one of the most important and widely used mainstream iterative search tool for protein sequence search, an accurate Position Specific Scoring Matrix (PSSM) is the key of PSI-BLAST. However, PSSMs containing non-homologous information obviously reduce the performance of PSI-BLAST for protein remote homology. RESULTS In order to further study this problem, we summarize three types of Incorrectly Selected Homology (ISH) errors in PSSMs. A new search tool Supervised-Manner-based Iterative BLAST (SMI-BLAST) is proposed based on PSI-BLAST for solving these errors. SMI-BLAST obviously outperforms PSI-BLAST on the Structural Classification of Proteins-extended (SCOPe) dataset. Compared with PSI-BLAST on the ISH error subsets of SCOPe dataset, SMI-BLAST detects 1.6∼2.87 folds more remote homologous sequences, and outperforms PSI-BLAST by 35.66% in terms of ROC1 scores. Furthermore, this framework is applied to JackHMMER, DELTA-BLAST and PSI-BLASTexB, and their performance is further improved. AVAILABILITY AND IMPLEMENTATION User-friendly webservers for SMI-BLAST, JackHMMER, DELTA-BLAST and PSI-BLASTexB are established at http://bliulab.net/SMI-BLAST/, by which the users can easily get the results without the need to go through the mathematical details. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.