title: The importance of physicochemical characteristics and nonlinear classifiers in determining HIV-1 protease specificity.
abstract: This paper reviews recent research relating to the application of bioinformatics approaches to determining HIV-1 protease specificity, outlines outstanding issues, and presents a new approach to addressing these issues. Leading machine learning theory for the problem currently suggests that the direct encoding of the physicochemical properties of the amino acid substrates is not required for optimal performance. A number of amino acid encoding approaches which incorporate potentially relevant physicochemical properties of the substrate are identified, and are evaluated using a nonlinear task decomposition based neuroevolution algorithm. The results are evaluated, and compared against a recent benchmark set on a nonlinear classifier using only amino acid sequence and identity information. Ensembles of these nonlinear classifiers using the physicochemical properties of the substrate are demonstrated to consistently outperform the recently published state-of-the-art linear support vector machine based approach in out-of-sample evaluations.
authors.affiliation: a Department of Computer Science , Cork Institute of Technology , Cork , Ireland.
authors.forename: Timmy
authors.initials: T
authors.lastname: Manning
authors.affiliation: a Department of Computer Science , Cork Institute of Technology , Cork , Ireland.|b NSilico Ltd, Rubicon Innovation Center , Cork , Ireland.
authors.forename: Paul
authors.initials: P
authors.lastname: Walsh
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D001185:Artificial Intelligence; D020539:Sequence Analysis, Protein; D060388:Support Vector Machine
keywords: HIV-1; SVM; amino acid encoding; neural networks; physicochemical; protease specificity