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.

On the difficulty of feature-based attentional modulations in visual object recognition: A modeling study.

Numerous psychophysical experiments have shown an important role for attentional modulations in vision. Behaviorally, allocation of attention can improve performance in object detection and recognition tasks. At the neural level, attention increases firing rates of neurons in visual cortex whose preferred stimulus is currently attended to. However, it is not yet known how these two phenomena are linked, i.e., how the visual system could be "tuned" in a task-dependent fashion to improve task performance. To answer this question, we performed simulations with the HMAX model of object recognition in cortex [45]. We modulated firing rates of model neurons in accordance with experimental results about effects of feature-based attention on single neurons and measured changes in the model's performance in a variety of object recognition tasks. It turned out that recognition performance could only be improved under very limited circumstances and that attentional influences on the process of object recognition per se tend to display a lack of specificity or raise false alarm rates. These observations lead us to postulate a new role for the observed attention-related neural response modulations.

Incremental Verification of Timing Constraints for Real-Time Systems

Testing constraints for real-time systems are usually verified through the satisfiability of propositional formulae. In this paper, we propose an alternative where the verification of timing constraints can be done by counting the number of truth assignments instead of boolean satisfiability. This number can also tell us how “far away” is a given specification from satisfying its safety assertion. Furthermore, specifications and safety assertions are often modified in an incremental fashion, where problematic bugs are fixed one at a time. To support this development, we propose an incremental algorithm for counting satisfiability. Our proposed incremental algorithm is optimal as no unnecessary nodes are created during each counting. This works for the class of path RTL. To illustrate this application, we show how incremental satisfiability counting can be applied to a well-known rail-road crossing example, particularly when its specification is still being refined.

Protein Microarray: "Theory" to "Real Practice"

Fueled by ever-growing genomic information and rapid developments of proteomics–the large scale analysis of proteins and mapping its functional role has become one of the most important disciplines for characterizing complex cell function. For building functional linkages between the biomolecules, and for providing insight into the mechanisms of biological processes, last decade witnessed the exploration of combinatorial and chip technology for the detection of bimolecules in a high throughput and spatially addressable fashion. Among the various techniques developed, the protein chip technology has been rapid. Recently we demonstrated a new platform called “Spacially addressable protein array” (SAPA) to profile the ligand receptor interactions. To optimize the platform, the present study investigated various parameters such as the surface chemistry and role of additives for achieving high density and high-throughput detection with minimal nonspecific protein adsorption. In summary the present poster will address some of the critical challenges in protein micro array technology and the process of fine tuning to achieve the optimum system for solving real biological problems.