Network-Based Genome Wide Study of Hippocampal Imaging Phenotype In Alzheimer's Disease To Identify Functional Interaction Modules

Identification of functional modules from biological network is a promising approach to enhance the statistical power of genome-wide association study (GWAS) and improve biological interpretation for complex diseases. The precise functions of genes are highly relevant to tissue context, while a majority of module identification studies are based on tissue-free biological networks that lacks phenotypic specificity. In this study, we propose a module identification method that maps the GWAS results of an imaging phenotype onto the corresponding tissue-specific functional interaction network by applying a machine learning framework. Ridge regression and support vector machine (SVM) models are constructed to re-prioritize GWAS results, followed by exploring hippocampus-relevant modules based on top predictions using GWAS top findings. We also propose a GWAS top-neighbor-based module identification approach and compare it with Ridge and SVM based approaches. Modules conserving both tissue specificity and GWAS discoveries are identified, showing the promise of the proposal method for providing insight into the mechanism of complex diseases

Self-organized Networks of Competing Boolean Agents

A model of Boolean agents competing in a market is presented where each agent bases his action on information obtained from a small group of other agents. The agents play a competitive game that rewards those in the minority. After a long time interval, the poorest player's strategy is changed randomly, and the process is repeated. Eventually the network evolves to a stationary but intermittent state where random mutation of the worst strategy can change the behavior of the entire network, often causing a switch in the dynamics between attractors of vastly different lengths.Comment: 4 pages, 3 included figures. Some text revision and one new figure added. To appear in PR

Emergence of Complex Dynamics in a Simple Model of Signaling Networks

A variety of physical, social and biological systems generate complex fluctuations with correlations across multiple time scales. In physiologic systems, these long-range correlations are altered with disease and aging. Such correlated fluctuations in living systems have been attributed to the interaction of multiple control systems; however, the mechanisms underlying this behavior remain unknown. Here, we show that a number of distinct classes of dynamical behaviors, including correlated fluctuations characterized by $1/f$-scaling of their power spectra, can emerge in networks of simple signaling units. We find that under general conditions, complex dynamics can be generated by systems fulfilling two requirements: i) a ``small-world'' topology and ii) the presence of noise. Our findings support two notable conclusions: first, complex physiologic-like signals can be modeled with a minimal set of components; and second, systems fulfilling conditions (i) and (ii) are robust to some degree of degradation, i.e., they will still be able to generate $1/f$-dynamics