Integration of relational and hierarchical network information for protein function prediction

BACKGROUND:In the current climate of high-throughput computational biology, the inference of a protein's function from related measurements, such as protein-protein interaction relations, has become a canonical task. Most existing technologies pursue this task as a classification problem, on a term-by-term basis, for each term in a database, such as the Gene Ontology (GO) database, a popular rigorous vocabulary for biological functions. However, ontology structures are essentially hierarchies, with certain top to bottom annotation rules which protein function predictions should in principle follow. Currently, the most common approach to imposing these hierarchical constraints on network-based classifiers is through the use of transitive closure to predictions.RESULTS:We propose a probabilistic framework to integrate information in relational data, in the form of a protein-protein interaction network, and a hierarchically structured database of terms, in the form of the GO database, for the purpose of protein function prediction. At the heart of our framework is a factorization of local neighborhood information in the protein-protein interaction network across successive ancestral terms in the GO hierarchy. We introduce a classifier within this framework, with computationally efficient implementation, that produces GO-term predictions that naturally obey a hierarchical 'true-path' consistency from root to leaves, without the need for further post-processing.CONCLUSION:A cross-validation study, using data from the yeast Saccharomyces cerevisiae, shows our method offers substantial improvements over both standard 'guilt-by-association' (i.e., Nearest-Neighbor) and more refined Markov random field methods, whether in their original form or when post-processed to artificially impose 'true-path' consistency. Further analysis of the results indicates that these improvements are associated with increased predictive capabilities (i.e., increased positive predictive value), and that this increase is consistent uniformly with GO-term depth. Additional in silico validation on a collection of new annotations recently added to GO confirms the advantages suggested by the cross-validation study. Taken as a whole, our results show that a hierarchical approach to network-based protein function prediction, that exploits the ontological structure of protein annotation databases in a principled manner, can offer substantial advantages over the successive application of 'flat' network-based methods.

Active Hidden Models for Tracking with Kernel Projections

We introduce Active Hidden Models (AHM) that utilize kernel methods traditionally associated with classification. We use AHMs to track deformable objects in video sequences by leveraging kernel projections. We introduce the "subset projection" method which improves the efficiency of our tracking approach by a factor of ten. We successfully tested our method on facial tracking with extreme head movements (including full 180-degree head rotation), facial expressions, and deformable objects. Given a kernel and a set of training observations, we derive unbiased estimates of the accuracy of the AHM tracker. Kernels are generally used in classification methods to make training data linearly separable. We prove that the optimal (minimum variance) tracking kernels are those that make the training observations linearly dependent.

An alignment based similarity measure for hand detection in cluttered sign language video

Locating hands in sign language video is challenging due to a number of factors. Hand appearance varies widely across signers due to anthropometric variations and varying levels of signer proficiency. Video can be captured under varying illumination, camera resolutions, and levels of scene clutter, e.g., high-res video captured in a studio vs. low-res video gathered by a web cam in a user’s home. Moreover, the signers’ clothing varies, e.g., skin-toned clothing vs. contrasting clothing, short-sleeved vs. long-sleeved shirts, etc. In this work, the hand detection problem is addressed in an appearance matching framework. The Histogram of Oriented Gradient (HOG) based matching score function is reformulated to allow non-rigid alignment between pairs of images to account for hand shape variation. The resulting alignment score is used within a Support Vector Machine hand/not-hand classifier for hand detection. The new matching score function yields improved performance (in ROC area and hand detection rate) over the Vocabulary Guided Pyramid Match Kernel (VGPMK) and the traditional, rigid HOG distance on American Sign Language video gestured by expert signers. The proposed match score function is computationally less expensive (for training and testing), has fewer parameters and is less sensitive to parameter settings than VGPMK. The proposed detector works well on test sequences from an inexpert signer in a non-studio setting with cluttered background.