Understanding Subsystems in Biology through Dimensionality Reduction, Graph Partitioning and Analytical Modeling

Biological systems exhibit rich and complex behavior through the orchestrated interplay of a large array of components. It is hypothesized that separable subsystems with some degree of functional autonomy exist; deciphering their independent behavior and functionality would greatly facilitate understanding the system as a whole. Discovering and analyzing such subsystems are hence pivotal problems in the quest to gain a quantitative understanding of complex biological systems. In this work, using approaches from machine learning, physics and graph theory, methods for the identification and analysis of such subsystems were developed. A novel methodology, based on a recent machine learning algorithm known as non-negative matrix factorization (NMF), was developed to discover such subsystems in a set of large-scale gene expression data. This set of subsystems was then used to predict functional relationships between genes, and this approach was shown to score significantly higher than conventional methods when benchmarking them against existing databases. Moreover, a mathematical treatment was developed to treat simple network subsystems based only on their topology (independent of particular parameter values). Application to a problem of experimental interest demonstrated the need for extentions to the conventional model to fully explain the experimental data. Finally, the notion of a subsystem was evaluated from a topological perspective. A number of different protein networks were examined to analyze their topological properties with respect to separability, seeking to find separable subsystems. These networks were shown to exhibit separability in a nonintuitive fashion, while the separable subsystems were of strong biological significance. It was demonstrated that the separability property found was not due to incomplete or biased data, but is likely to reflect biological structure.

Image Based Rendering Using Algebraic Techniques

This paper presents an image-based rendering system using algebraic relations between different views of an object. The system uses pictures of an object taken from known positions. Given three such images it can generate "virtual'' ones as the object would look from any position near the ones that the two input images were taken from. The extrapolation from the example images can be up to about 60 degrees of rotation. The system is based on the trilinear constraints that bind any three view so fan object. As a side result, we propose two new methods for camera calibration. We developed and used one of them. We implemented the system and tested it on real images of objects and faces. We also show experimentally that even when only two images taken from unknown positions are given, the system can be used to render the object from other view points as long as we have a good estimate of the internal parameters of the camera used and we are able to find good correspondence between the example images. In addition, we present the relation between these algebraic constraints and a factorization method for shape and motion estimation. As a result we propose a method for motion estimation in the special case of orthographic projection.