Detecting distant homology with Meta-BASIC
1 Department of Biochemistry and 2 Howard Hughes Medical Institute, University of Texas, Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, USA, 3 BioInfoBank Institute, ul. Limanowskiego 24A, 60-744 Pozna
, Poland and 4 Faculty of Physics, Adam Mickiewicz University, ul. Umultowska 85, 61-614 Pozna, Poland
* To whom correspondence should be addressed at BioInfoBank Institute, ul. Limanowskiego 24A, 60-744 Pozna, Poland. Tel: +48 61 8653520; Fax: +48 61 8643350; Email: kginal{at}bioinfo.pl
Correspondence may also be addressed to Leszek Rychlewski. Email: leszek{at}bioinfo.pl
Received January 31, 2004; Revised and Accepted March 9, 2004
Meta-BASIC (http://basic.bioinfo.pl) is a novel sensitive approach for recognition of distant similarity between proteins based on consensus alignments of meta profiles. Specifically, Meta-BASIC compares sequence profiles combined with predicted secondary structure by utilizing several scoring systems and alignment algorithms. In our benchmarking tests, Meta-BASIC outperforms many individual servers, including fold recognition servers, and it can compete with meta predictors that base their strength on the structural comparison of models. In addition, Meta-BASIC, which enables detection of very distant relationships even if the tertiary structure for the reference protein is not known, has a high-throughput capability. This new method is applied to 860 PfamA protein families with unknown function (DUF) and provides many novel structure–functional assignments available on-line at http://basic.bioinfo.pl/duf.pl. Detailed discussion is provided for two of the most interesting assignments. DUF271 and DUF431 are predicted to be a nucleotide-diphospho-sugar transferase and an 
/ß-knot SAM-dependent RNA methyltransferase, respectively.
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