Life Sciences Commons^™

Uncover Disease Genes By Maximizing Information Flow In The Phenome-Interactome Network., Yong Chen, Tao Jiang, Rui Jiang

College of Science & Mathematics Departmental Research

MOTIVATION: Pinpointing genes that underlie human inherited diseases among candidate genes in susceptibility genetic regions is the primary step towards the understanding of pathogenesis of diseases. Although several probabilistic models have been proposed to prioritize candidate genes using phenotype similarities and protein-protein interactions, no combinatorial approaches have been proposed in the literature.

RESULTS: We propose the first combinatorial approach for prioritizing candidate genes. We first construct a phenome-interactome network by integrating the given phenotype similarity profile, protein-protein interaction network and associations between diseases and genes. Then, we introduce a computational method called MAXIF to maximize the information flow in this …

Psychostimulants As Cognitive Enhancers: The Prefrontal Cortex, Catecholamines And Attention Deficit Hyperactivity Disorder, Craig Berridge, David M. Devilbiss

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Psychostimulants exert behavioral-calming and cognition-enhancing actions in the treatment of attention deficit hyperactivity disorder (ADHD). Contrary to early views, extensive research demonstrates that these actions are not unique to ADHD. Specifically, when administered at low and clinically-relevant doses, psychostimulants improve a variety of behavioral and cognitive processes dependent on the prefrontal cortex (PFC) in subjects with and without ADHD. Despite the longstanding clinical use of these drugs, the neural mechanisms underlying their cognition-enhancing/therapeutic actions have only recently begun to be examined. At behaviorally-activating doses, psychostimulants produce large and widespread increases in extracellular levels of brain catecholamines. In contrast, cognition-enhancing doses …

Domainrbf: A Bayesian Regression Approach To The Prioritization Of Candidate Domains For Complex Diseases., Wangshu Zhang, Yong Chen, Fengzhu Sun, Rui Jiang

College of Science & Mathematics Departmental Research

BACKGROUND: Domains are basic units of proteins, and thus exploring associations between protein domains and human inherited diseases will greatly improve our understanding of the pathogenesis of human complex diseases and further benefit the medical prevention, diagnosis and treatment of these diseases. Within a given domain-domain interaction network, we make the assumption that similarities of disease phenotypes can be explained using proximities of domains associated with such diseases. Based on this assumption, we propose a Bayesian regression approach named "domainRBF" (domain Rank with Bayes Factor) to prioritize candidate domains for human complex diseases.

RESULTS: Using a compiled dataset containing 1,614 …

Genome-Wide Discovery Of Missing Genes In Biological Pathways Of Prokaryotes., Yong Chen, Fenglou Mao, Guojun Li, Ying Xu

College of Science & Mathematics Departmental Research

BACKGROUND: Reconstruction of biological pathways is typically done through mapping well-characterized pathways of model organisms to a target genome, through orthologous gene mapping. A limitation of such pathway-mapping approaches is that the mapped pathway models are constrained by the composition of the template pathways, e.g., some genes in a target pathway may not have corresponding genes in the template pathways, the so-called "missing gene" problem.

METHODS: We present a novel pathway-expansion method for identifying additional genes that are possibly involved in a target pathway after pathway mapping, to fill holes caused by missing genes as well as to expand the …