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.

Parallelism in Manipulator Dynamics

This paper addresses the problem of efficiently computing the motor torques required to drive a lower-pair kinematic chain (e.g., a typical manipulator arm in free motion, or a mechanical leg in the swing phase) given the desired trajectory; i.e., the Inverse Dynamics problem. It investigates the high degree of parallelism inherent in the computations, and presents two "mathematically exact" formulations especially suited to high-speed, highly parallel implementations using special-purpose hardware or VLSI devices. In principle, the formulations should permit the calculations to run at a speed bounded only by I/O. The first presented is a parallel version of the recent linear Newton-Euler recursive algorithm. The time cost is also linear in the number of joints, but the real-time coefficients are reduced by almost two orders of magnitude. The second formulation reports a new parallel algorithm which shows that it is possible to improve upon the linear time dependency. The real time required to perform the calculations increases only as the [log2] of the number of joints. Either formulation is susceptible to a systolic pipelined architecture in which complete sets of joint torques emerge at successive intervals of four floating-point operations. Hardware requirements necessary to support the algorithm are considered and found not to be excessive, and a VLSI implementation architecture is suggested. We indicate possible applications to incorporating dynamical considerations into trajectory planning, e.g. it may be possible to build an on-line trajectory optimizer.