Neural Network and Bioinformatic Methods for Predicting HIV-1 Protease Inhibitor Resistance

This article presents a new method for predicting viral resistance to seven protease inhibitors from the HIV-1 genotype, and for identifying the positions in the protease gene at which the specific nature of the mutation affects resistance. The neural network Analog ARTMAP predicts protease inhibitor resistance from viral genotypes. A feature selection method detects genetic positions that contribute to resistance both alone and through interactions with other positions. This method has identified positions 35, 37, 62, and 77, where traditional feature selection methods have not detected a contribution to resistance. At several positions in the protease gene, mutations confer differing degress of resistance, depending on the specific amino acid to which the sequence has mutated. To find these positions, an Amino Acid Space is introduced to represent genes in a vector space that captures the functional similarity between amino acid pairs. Feature selection identifies several new positions, including 36, 37, and 43, with amino acid-specific contributions to resistance. Analog ARTMAP networks applied to inputs that represent specific amino acids at these positions perform better than networks that use only mutation locations.

Modal Matching for Correspondence and Recognition

Modal matching is a new method for establishing correspondences and computing canonical descriptions. The method is based on the idea of describing objects in terms of generalized symmetries, as defined by each object's eigenmodes. The resulting modal description is used for object recognition and categorization, where shape similarities are expressed as the amounts of modal deformation energy needed to align the two objects. In general, modes provide a global-to-local ordering of shape deformation and thus allow for selecting which types of deformations are used in object alignment and comparison. In contrast to previous techniques, which required correspondence to be computed with an initial or prototype shape, modal matching utilizes a new type of finite element formulation that allows for an object's eigenmodes to be computed directly from available image information. This improved formulation provides greater generality and accuracy, and is applicable to data of any dimensionality. Correspondence results with 2-D contour and point feature data are shown, and recognition experiments with 2-D images of hand tools and airplanes are described.