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.

A Customizable Camera-based Human Computer Interaction System Allowing People With Disabilities Autonomous Hands Free Navigation of Multiple Computing Task

Many people suffer from conditions that lead to deterioration of motor control and makes access to the computer using traditional input devices difficult. In particular, they may loose control of hand movement to the extent that the standard mouse cannot be used as a pointing device. Most current alternatives use markers or specialized hardware to track and translate a user's movement to pointer movement. These approaches may be perceived as intrusive, for example, wearable devices. Camera-based assistive systems that use visual tracking of features on the user's body often require cumbersome manual adjustment. This paper introduces an enhanced computer vision based strategy where features, for example on a user's face, viewed through an inexpensive USB camera, are tracked and translated to pointer movement. The main contributions of this paper are (1) enhancing a video based interface with a mechanism for mapping feature movement to pointer movement, which allows users to navigate to all areas of the screen even with very limited physical movement, and (2) providing a customizable, hierarchical navigation framework for human computer interaction (HCI). This framework provides effective use of the vision-based interface system for accessing multiple applications in an autonomous setting. Experiments with several users show the effectiveness of the mapping strategy and its usage within the application framework as a practical tool for desktop users with disabilities.