Improving functional annotation of no n-s yno no mo us s nps with information theory

R. Karchin, L. Kelly, A. Sali

Research output: Chapter in Book/Report/Conference proceedingConference contribution

39 Scopus citations

Abstract

Automated functional annotation of nsSNPs requires that amino-acid residue changes are represented by a set of descriptive features, such as evolutionary conservation, side-chain volume change, effect on ligand-binding, and residue structural rigidity. Identifying the most informative combinations of features is critical to the success of a computational prediction method. We rank 32 features according to their mutual information with functional effects of amino-acid substitutions, as measured by in vivo assays. In addition, we use a greedy algorithm to identify a subset of highly informative features [1], The method is simple to implement and provides a quantitative measure for selecting the best predictive features given a set of features that a human expert believes to be informative. We demonstrate the usefulness of the selected highly informative features by cross-validated tests of a computational classifier, a support vector machine (SVM). The SVM's classification accuracy is highly correlated with the ranking of the input features by their mutual information. Two features describing the solvent accessibility of "wild-type" and "mutant" amino-acid residues and one evolutionary feature based on superfamily-level multiple alignments produce comparable overall accuracy and 6% fewer false positives than a 32- feature set that considers physiochemical properties of amino acids, protein electrostatics, amino-acid residue flexibility, and binding interactions.

Original languageEnglish (US)
Title of host publicationProceedings of the Pacific Symposium on Biocomputing 2005, PSB 2005
Pages397-408
Number of pages12
StatePublished - Dec 1 2005
Externally publishedYes
Event10th Pacific Symposium on Biocomputing, PSB 2005 - Big Island of Hawaii, United States
Duration: Jan 4 2005Jan 8 2005

Publication series

NameProceedings of the Pacific Symposium on Biocomputing 2005, PSB 2005

Other

Other10th Pacific Symposium on Biocomputing, PSB 2005
CountryUnited States
CityBig Island of Hawaii
Period1/4/051/8/05

ASJC Scopus subject areas

  • Computational Theory and Mathematics
  • Biomedical Engineering

Fingerprint Dive into the research topics of 'Improving functional annotation of no n-s yno no mo us s nps with information theory'. Together they form a unique fingerprint.

  • Cite this

    Karchin, R., Kelly, L., & Sali, A. (2005). Improving functional annotation of no n-s yno no mo us s nps with information theory. In Proceedings of the Pacific Symposium on Biocomputing 2005, PSB 2005 (pp. 397-408). (Proceedings of the Pacific Symposium on Biocomputing 2005, PSB 2005).