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.

Towards a Computational Theory of Definite Anaphora Comprehension in English Discourse

This report investigates the process of focussing as a description and explanation of the comprehension of certain anaphoric expressions in English discourse. The investigation centers on the interpretation of definite anaphora, that is, on the personal pronouns, and noun phrases used with a definite article the, this or that. Focussing is formalized as a process in which a speaker centers attention on a particular aspect of the discourse. An algorithmic description specifies what the speaker can focus on and how the speaker may change the focus of the discourse as the discourse unfolds. The algorithm allows for a simple focussing mechanism to be constructed: and element in focus, an ordered collection of alternate foci, and a stack of old foci. The data structure for the element in focus is a representation which encodes a limted set of associations between it and other elements from teh discourse as well as from general knowledge.