<p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p> <p>The analysis of genomics data needs to become as automated as its generation. Here we present a novel data-mining approach to predicting protein functional class from sequence. This method is based on a combination of inductive logic programming clustering and rule learning. We demonstrate the effectiveness of this approach on the <italic>M. tuberculosis</italic> and <italic>E. coli</italic> genomes, and identify biologically interpretable rules which predict protein functional class from information only available from the sequence. These rules predict 65% of the ORFs with no assigned function in <italic>M. tuberculosis</italic> and 24% of those in <italic>E. coli</italic>, with an estimated accuracy of 60–80% (depending on the level of functional assignment). The rules are founded on a combination of detection of remote homology, convergent evolution and horizontal gene transfer. We identify rules that predict protein functional class even in the absence of detectable sequence or structural homology. These rules give insight into the evolutionary history of <italic>M. tuberculosis</italic> and <italic>E. coli</italic>.</p>
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Yeast. 2000; 17(4):283-293