Network Topology in Cell Signaling. Start date: April 15, 2007. Expires: March 31, 2009. Amount: $291,820. Principal investigator: Norbert Perrimon. Institution: Harvard University Medical School. NIH institute: NIDDK.
Proposal to reconstruct the insulin-signaling network in Drosophila tissue culture cells based on transcriptional responses associated with the reduction of those components by RNA interference. The network will be built by using gene-specific dsRNAs to successively perturb each of the 261 kinase and PPase that are expressed in the Drosophila SL2 cell line. Computational network-modeling algorithms will be used to convert gene-expression profiles into network connectivities.
A Partially Linear Tree-based Regression Model for Assessing Complex Joint Gene-Gene Interactions. Start date: May 1, 2007. Expires: April 30, 2009. Amount: $78,709. Principal investigator: Jinbo Chen. Institution: University of Pennsylvania. NIH institute: NCI.
Funds development of a new class of semiparametric regression models, partially linear tree-based regression models, “that has the advantages of both generalized linear regression and tree models,” according to the grant abstract. A PLTR model quantifies joint effects of genes by a combination of linear main effects and a nonparametric tree-structure. The project will assess an iterative algorithm to fit the PLTR model and develop methods for identifying and testing the significance of an optimal-pruned tree nested within the tree resultant from the fitting algorithm. The method will be used to analyze several cancer genetic epidemiology studies to explore joint gene-gene or gene-environment interactions.
Building Motif Lexicons. Start date: May 1, 2007. Expires: April 30, 2011. Amount: $288,025. Principal investigator: Martin Schiller. Institution: University of Connecticut School of Medicine and Dentistry. NIH institute: NIGMS.
Supports continued development of Minimotif Miner, a short motif database and platform-independent web-tool that identifies motif consensus sequences in protein queries. MnM can be used to identify protein functions, to develop new hypotheses of how specific mutations cause human disease, and to identify putative targets for the development of therapeutic drugs, antibiotics, insecticides, and antiviral agents. The investigators plan to reduce the false-positive prediction of motifs via the creation of a new language that accounts for the three-dimensional structural conservation of motifs.
The Epilepsy Phenome/ Genome Project (EPGP). Start date: May 1, 2007. Expires: April 30, 2012. Amount: $3,992,596. Principal investigator: Daniel Lowenstein. Institution: University of California, San Francisco. NIH institute: NINDS.
Supports the Epilepsy Phenome/Genome Project, a multi-institutional research project to study the genetic basis of epilepsy. The project will collect phenotypic information from 3,750 epilepsy patients and 3,000 controls, and use genomic and computational methods to identify how genetic variation contributes to the epilepsy phenotype, developmental anomalies of the brain, and the varied therapeutic response of patients.
Statistical & Computational Tools for Reconstruction of Gene Regulatory Networks. Start date: July 1, 2007. Expires: June 30, 2008. Amount: $71,960. Principal investigator: Peter Salzman. Institution: University of Rochester. NIH institute: NLM
Funds a project to “address the theoretical and computational issues arising in the reconstruction of regulatory networks,” according to the grant abstract. The investigator plans to develop “theoretically based scores for network reconstruction in a frequentist and Bayesian framework.” The investigator has proposed an implementation of the simulated annealing and Markov chain Monte Carlo algorithms “that works on a reduced space of orders and thus increases the efficiency.”