Combining pairwise sequence similarity and support vector machines for remote protein homology detection

  • Authors:
  • Li Liao;William Stafford Noble

  • Affiliations:
  • E. I. du Pont de Nemours Company;Columbia University

  • Venue:
  • Proceedings of the sixth annual international conference on Computational biology
  • Year:
  • 2002

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Abstract

One key element in understanding the molecular machinery of the cell is to understand the meaning, or function, of each protein encoded in the genome. A very successful means of inferring the function of a previously unannotated protein is via sequence similarity with one or more proteins whose functions are already known. Currently, one of the most powerful such homology detection methods is the SVM-Fisher method of Jaakkola, Diekhans and Haussler (ISMB 2000). This method combines a generative, profile hidden Markov model (HMM) with a discriminative classification algorithm known as a support vector machine (SVM). The current work presents an alternative method for SVM-based protein classification. The method, SVM-pairwise, uses a pairwise sequence similarity algorithm such as Smith-Waterman in place of the HMM in the SVM-Fisher method. The resulting algorithm, when tested on its ability to recognize previously unseen families from the SCOP database, yields significantly better remote protein homology detection than SVM-Fisher, profile HMMs and PSI-BLAST.