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.

Skin Color-Based Video Segmentation under Time-Varying Illumination

A novel approach for real-time skin segmentation in video sequences is described. The approach enables reliable skin segmentation despite wide variation in illumination during tracking. An explicit second order Markov model is used to predict evolution of the skin-color (HSV) histogram over time. Histograms are dynamically updated based on feedback from the current segmentation and predictions of the Markov model. The evolution of the skin-color distribution at each frame is parameterized by translation, scaling and rotation in color space. Consequent changes in geometric parameterization of the distribution are propagated by warping and resampling the histogram. The parameters of the discrete-time dynamic Markov model are estimated using Maximum Likelihood Estimation, and also evolve over time. The accuracy of the new dynamic skin color segmentation algorithm is compared to that obtained via a static color model. Segmentation accuracy is evaluated using labeled ground-truth video sequences taken from staged experiments and popular movies. An overall increase in segmentation accuracy of up to 24% is observed in 17 out of 21 test sequences. In all but one case the skin-color classification rates for our system were higher, with background classification rates comparable to those of the static segmentation.

Discovering Clusters in Motion Time-Series Data

A new approach is proposed for clustering time-series data. The approach can be used to discover groupings of similar object motions that were observed in a video collection. A finite mixture of hidden Markov models (HMMs) is fitted to the motion data using the expectation-maximization (EM) framework. Previous approaches for HMM-based clustering employ a k-means formulation, where each sequence is assigned to only a single HMM. In contrast, the formulation presented in this paper allows each sequence to belong to more than a single HMM with some probability, and the hard decision about the sequence class membership can be deferred until a later time when such a decision is required. Experiments with simulated data demonstrate the benefit of using this EM-based approach when there is more "overlap" in the processes generating the data. Experiments with real data show the promising potential of HMM-based motion clustering in a number of applications.

A Bayesian Approach for TCP to Distinguish Congestion from Wireless Losses

(This Technical Report revises TR-BUCS-2003-011) The Transmission Control Protocol (TCP) has been the protocol of choice for many Internet applications requiring reliable connections. The design of TCP has been challenged by the extension of connections over wireless links. In this paper, we investigate a Bayesian approach to infer at the source host the reason of a packet loss, whether congestion or wireless transmission error. Our approach is "mostly" end-to-end since it requires only one long-term average quantity (namely, long-term average packet loss probability over the wireless segment) that may be best obtained with help from the network (e.g. wireless access agent).Specifically, we use Maximum Likelihood Ratio tests to evaluate TCP as a classifier of the type of packet loss. We study the effectiveness of short-term classification of packet errors (congestion vs. wireless), given stationary prior error probabilities and distributions of packet delays conditioned on the type of packet loss (measured over a larger time scale). Using our Bayesian-based approach and extensive simulations, we demonstrate that congestion-induced losses and losses due to wireless transmission errors produce sufficiently different statistics upon which an efficient online error classifier can be built. We introduce a simple queueing model to underline the conditional delay distributions arising from different kinds of packet losses over a heterogeneous wired/wireless path. We show how Hidden Markov Models (HMMs) can be used by a TCP connection to infer efficiently conditional delay distributions. We demonstrate how estimation accuracy is influenced by different proportions of congestion versus wireless losses and penalties on incorrect classification.

End-to-End Inference of Loss Nature in a Hybrid Wired/Wireless Environment

End-to-End differentiation between wireless and congestion loss can equip TCP control so it operates effectively in a hybrid wired/wireless environment. Our approach integrates two techniques: packet loss pairs (PLP) and Hidden Markov Modeling (HMM). A packet loss pair is formed by two back-to-back packets, where one packet is lost while the second packet is successfully received. The purpose is for the second packet to carry the state of the network path, namely the round trip time (RTT), at the time the other packet is lost. Under realistic conditions, PLP provides strong differentiation between congestion and wireless type of loss based on distinguishable RTT distributions. An HMM is then trained so observed RTTs can be mapped to model states that represent either congestion loss or wireless loss. Extensive simulations confirm the accuracy of our HMM-based technique in classifying the cause of a packet loss. We also show the superiority of our technique over the Vegas predictor, which was recently found to perform best and which exemplifies other existing loss labeling techniques.

Layered Graphical Models for Tracking Partially-Occluded Objects

Partial occlusions are commonplace in a variety of real world computer vision applications: surveillance, intelligent environments, assistive robotics, autonomous navigation, etc. While occlusion handling methods have been proposed, most methods tend to break down when confronted with numerous occluders in a scene. In this paper, a layered image-plane representation for tracking people through substantial occlusions is proposed. An image-plane representation of motion around an object is associated with a pre-computed graphical model, which can be instantiated efficiently during online tracking. A global state and observation space is obtained by linking transitions between layers. A Reversible Jump Markov Chain Monte Carlo approach is used to infer the number of people and track them online. The method outperforms two state-of-the-art methods for tracking over extended occlusions, given videos of a parking lot with numerous vehicles and a laboratory with many desks and workstations.

Estimation and Prediction of Evolving Color Distributions for Skin Segmentation Under Varying Illumination

A novel approach for real-time skin segmentation in video sequences is described. The approach enables reliable skin segmentation despite wide variation in illumination during tracking. An explicit second order Markov model is used to predict evolution of the skin color (HSV) histogram over time. Histograms are dynamically updated based on feedback from the current segmentation and based on predictions of the Markov model. The evolution of the skin color distribution at each frame is parameterized by translation, scaling and rotation in color space. Consequent changes in geometric parameterization of the distribution are propagated by warping and re-sampling the histogram. The parameters of the discrete-time dynamic Markov model are estimated using Maximum Likelihood Estimation, and also evolve over time. Quantitative evaluation of the method was conducted on labeled ground-truth video sequences taken from popular movies.

MosaicShape: Stochastic Region Grouping with Shape Prior

A novel method that combines shape-based object recognition and image segmentation is proposed for shape retrieval from images. Given a shape prior represented in a multi-scale curvature form, the proposed method identifies the target objects in images by grouping oversegmented image regions. The problem is formulated in a unified probabilistic framework and solved by a stochastic Markov Chain Monte Carlo (MCMC) mechanism. By this means, object segmentation and recognition are accomplished simultaneously. Within each sampling move during the simulation process,probabilistic region grouping operations are influenced by both the image information and the shape similarity constraint. The latter constraint is measured by a partial shape matching process. A generalized parallel algorithm by Barbu and Zhu,combined with a large sampling jump and other implementation improvements, greatly speeds up the overall stochastic process. The proposed method supports the segmentation and recognition of multiple occluded objects in images. Experimental results are provided for both synthetic and real images.

Spatiotemporal Gesture Segmentation

Spotting patterns of interest in an input signal is a very useful task in many different fields including medicine, bioinformatics, economics, speech recognition and computer vision. Example instances of this problem include spotting an object of interest in an image (e.g., a tumor), a pattern of interest in a time-varying signal (e.g., audio analysis), or an object of interest moving in a specific way (e.g., a human's body gesture). Traditional spotting methods, which are based on Dynamic Time Warping or hidden Markov models, use some variant of dynamic programming to register the pattern and the input while accounting for temporal variation between them. At the same time, those methods often suffer from several shortcomings: they may give meaningless solutions when input observations are unreliable or ambiguous, they require a high complexity search across the whole input signal, and they may give incorrect solutions if some patterns appear as smaller parts within other patterns. In this thesis, we develop a framework that addresses these three problems, and evaluate the framework's performance in spotting and recognizing hand gestures in video. The first contribution is a spatiotemporal matching algorithm that extends the dynamic programming formulation to accommodate multiple candidate hand detections in every video frame. The algorithm finds the best alignment between the gesture model and the input, and simultaneously locates the best candidate hand detection in every frame. This allows for a gesture to be recognized even when the hand location is highly ambiguous. The second contribution is a pruning method that uses model-specific classifiers to reject dynamic programming hypotheses with a poor match between the input and model. Pruning improves the efficiency of the spatiotemporal matching algorithm, and in some cases may improve the recognition accuracy. The pruning classifiers are learned from training data, and cross-validation is used to reduce the chance of overpruning. The third contribution is a subgesture reasoning process that models the fact that some gesture models can falsely match parts of other, longer gestures. By integrating subgesture reasoning the spotting algorithm can avoid the premature detection of a subgesture when the longer gesture is actually being performed. Subgesture relations between pairs of gestures are automatically learned from training data. The performance of the approach is evaluated on two challenging video datasets: hand-signed digits gestured by users wearing short sleeved shirts, in front of a cluttered background, and American Sign Language (ASL) utterances gestured by ASL native signers. The experiments demonstrate that the proposed method is more accurate and efficient than competing approaches. The proposed approach can be generally applied to alignment or search problems with multiple input observations, that use dynamic programming to find a solution.

Object Detection at the Optimal Scale with Hidden State Shape Models

Hidden State Shape Models (HSSMs) [2], a variant of Hidden Markov Models (HMMs) [9], were proposed to detect shape classes of variable structure in cluttered images. In this paper, we formulate a probabilistic framework for HSSMs which provides two major improvements in comparison to the previous method [2]. First, while the method in [2] required the scale of the object to be passed as an input, the method proposed here estimates the scale of the object automatically. This is achieved by introducing a new term for the observation probability that is based on a object-clutter feature model. Second, a segmental HMM [6, 8] is applied to model the "duration probability" of each HMM state, which is learned from the shape statistics in a training set and helps obtain meaningful registration results. Using a segmental HMM provides a principled way to model dependencies between the scales of different parts of the object. In object localization experiments on a dataset of real hand images, the proposed method significantly outperforms the method of [2], reducing the incorrect localization rate from 40% to 15%. The improvement in accuracy becomes more significant if we consider that the method proposed here is scale-independent, whereas the method of [2] takes as input the scale of the object we want to localize.