Remote homology detection using a kernel method that combines sequence and secondary-structure similarity scores.
Distant evolutionary relationships between proteins with low sequence similarity are difficult to recognise by computational methods. Consequently, many sequences obtained from large-scale sequencing projects cannot be assigned to any known proteins or families despite being evolutionarily related. To boost sensitivity, various sequence-based methods have been modified to make use of the better conserved secondary structure. Most of these methods are instance-based or generative. Here, we introduce a kernel-based remote homology detection method that allows for a combination of sequence and secondary-structure similarity scores in a discriminative approach. We studied the ability of the method to predict superfamily membership as defined by the SCOP database. We show that a kernel method that combined sequence similarity scores with predicted secondary-structure similarity scores performed similar to a classifier that used scores calculated from sequences and true secondary structures, but performed better than a sequence-only based classifier and achieved a better mean than recently published results on the same data-set. It can be concluded that SVM classifiers trained to predict homology between distantly related proteins, become more accurate, if a joint sequence/secondary-structure similarity score approach is used.
The European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK. dwieser@ebi.ac.uk
Daniela
D
Wieser
Mahesan
M
Niranjan
D000595:Amino Acid Sequence; D000818:Animals; D019540:Area Under Curve; D019295:Computational Biology / Q000379:methods; D006454:Hemoglobins / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D009211:Myoglobin / Q000737:chemistry; D017433:Protein Structure, Secondary; D011506:Proteins / Q000145:classification*; D012372:ROC Curve; D017386:Sequence Homology, Amino Acid; D012984:Software
D006454:Hemoglobins; D009211:Myoglobin; D011506:Proteins