The feasibility of genome-scale biological network inference using Graphics Processing Units.

Systems research spanning fields from biology to finance involves the identification of models to represent the underpinnings of complex systems. Formal approaches for data-driven identification of network interactions include statistical inference-based approaches and methods to identify dynamical systems models that are capable of fitting multivariate data. Availability of large data sets and so-called 'big data' applications in biology present great opportunities as well as major challenges for systems identification/reverse engineering applications. For example, both inverse identification and forward simulations of genome-scale gene regulatory network models pose compute-intensive problems. This issue is addressed here by combining the processing power of Graphics Processing Units (GPUs) and a parallel reverse engineering algorithm for inference of regulatory networks. It is shown that, given an appropriate data set, information on genome-scale networks (systems of 1000 or more state variables) can be inferred using a reverse-engineering algorithm in a matter of days on a small-scale modern GPU cluster.

Big Data Analytics in Healthcare.

The rapidly expanding field of big data analytics has started to play a pivotal role in the evolution of healthcare practices and research. It has provided tools to accumulate, manage, analyze, and assimilate large volumes of disparate, structured, and unstructured data produced by current healthcare systems. Big data analytics has been recently applied towards aiding the process of care delivery and disease exploration. However, the adoption rate and research development in this space is still hindered by some fundamental problems inherent within the big data paradigm. In this paper, we discuss some of these major challenges with a focus on three upcoming and promising areas of medical research: image, signal, and genomics based analytics. Recent research which targets utilization of large volumes of medical data while combining multimodal data from disparate sources is discussed. Potential areas of research within this field which have the ability to provide meaningful impact on healthcare delivery are also examined.

The inferred cardiogenic gene regulatory network in the mammalian heart.

Cardiac development is a complex, multiscale process encompassing cell fate adoption, differentiation and morphogenesis. To elucidate pathways underlying this process, a recently developed algorithm to reverse engineer gene regulatory networks was applied to time-course microarray data obtained from the developing mouse heart. Approximately 200 genes of interest were input into the algorithm to generate putative network topologies that are capable of explaining the experimental data via model simulation. To cull specious network interactions, thousands of putative networks are merged and filtered to generate scale-free, hierarchical networks that are statistically significant and biologically relevant. The networks are validated with known gene interactions and used to predict regulatory pathways important for the developing mammalian heart. Area under the precision-recall curve and receiver operator characteristic curve are 9% and 58%, respectively. Of the top 10 ranked predicted interactions, 4 have already been validated. The algorithm is further tested using a network enriched with known interactions and another depleted of them. The inferred networks contained more interactions for the enriched network versus the depleted network. In all test cases, maximum performance of the algorithm was achieved when the purely data-driven method of network inference was combined with a data-independent, functional-based association method. Lastly, the network generated from the list of approximately 200 genes of interest was expanded using gene-profile uniqueness metrics to include approximately 900 additional known mouse genes and to form the most likely cardiogenic gene regulatory network. The resultant network supports known regulatory interactions and contains several novel cardiogenic regulatory interactions. The method outlined herein provides an informative approach to network inference and leads to clear testable hypotheses related to gene regulation.

Micellization kinetics of diblock copolymers in a homopolymer matrix: a self-consistent field study.

Self-consistent field theory is used to calculate free energy barriers and reaction rates for the spontaneous association and dissociation of micelles formed of block copolymers in a homopolymer matrix. The barriers are prohibitively large for copolymers of typical molecular weights when the unimer (free surfactant) concentration is near the equilibrium critical micelle concentration (CMC). As a result, polymeric micelles normally cannot reach true thermodynamic equilibrium. The rates of association and dissociation are, however, sensitive to unimer concentration, making it possible to form or destroy micelles at observable rates in sufficiently highly supersaturated or subsaturated solutions, respectively, even when both reactions are suppressed near the equilibrium CMC. The barrier to dissociation is particularly sensitive to unimer concentration, and vanishes when the unimer concentration is only slightly (for example, a percentage of a few tens) below the equilibrium CMC.