Machine Learning and Visualization in Structural Biology. Start date: April 1, 2006. Expires: March 31, 2010. Amount: $322,749. Principal investigator: Jude Shavlik. Institution: University of Wisconsin, Madison. NIH institute: NLM.
Proposal to develop computerized tools that assist X-ray crystallographers rapidly determine the three-dimensional structure of a protein. The project will create automated methods based both on statistical machine-learning and computer-vision techniques, as well as visualization tools.
Genomewide discovery and analysis of alternative promoters. Start date: April 27, 2006. Expires: Feb. 28, 2010. Amount: $325,000. Principal investigator: Ramana Davuluri. Institution: Ohio State University. NIH institute: NHGRI.
Basing their research on the hypothesis that the core promoter regions necessary for gene transcription are conserved between human and mouse, the investigators will use computational approaches to mine both human and mouse genomes to identify functional orthologous sequences. The derived information will be added into a prototype database for mammalian promoters, called MPromDb. The researchers will also develop computational tools for annotating experimentally known alternative promoters and first exons as well as computational methods to detect alternative promoters and first exons in the human and mouse genomes.
Experimental/Computational Study of Protein Aggregation. Start date: May 1, 2006. Expires: April 30, 2010. Amount: $261,910. Principal investigator: Teresa Head-Gordon. Institution: University of California, Berkeley. NIH institute: NIGMS.
Supports joint experimental and computational studies to examine the molecular mechanisms and the structural characteristics of protofibril and early events of amyloid fibril formation. Experiments and computer simulations of the immunoglobulin-binding proteins L and G will examine the effect of mutating protein sequence on nucleation events, aggregation propensity, the kinetics of aggregation and folding, and the role of folding intermediates on aggregation. Once validated by experiment, simulations will provide a rapid screening for sequences that minimize aggregation. "Using our computational results and those from other protein engineering studies, we will construct a set of guidelines for the rational design of mutations for reducing the aggregation propensity of a given protein, and test the transferability of these guidelines using a wide-range of mutants for proteins G," according to the grant abstract.
Computational Modeling of Developmental Processes. Start date: May 1, 2006. Expires: April 30, 2010. Amount: $312,240. Principal investigator: Larry Taber. Institution: Washington University. NIH institute: NIGMS.
Proposal to develop a general finite element code that can be used to model the biomechanics of developing soft tissue structures. The nonlinear finite element code will include volumetric growth, active contraction, and remodeling of individual tissue constituents. "The end result of this project will be the first general purpose tissue-level computer code for modeling the biomechanics of development," according to the abstract.
Public HIV Drug Resistance Database. Start date: May 1, 2006. Expires: April 30, 2011. Amount: $645,430. Principal investigator: Robert Shafer. Institution: Stanford University. NIH institute: NIAID.
Funds the expansion of the Stanford HIV RT and Protease Sequence Database "to represent, store, and analyze the diverse forms of data underlying drug resistance knowledge," according to the grant abstract. Improved methods for representing published drug resistance data, performing temporal queries and knowledge discovery, and for analyzing genotypic resistance data in a phylogenetic context will be implemented.
Continued Development of the Celera Whole Genome Shotgun Assembler. Start date: May 11, 2006. Expires: April 30, 2009. Amount: $245,998. Principal investigator: Granger Sutton. Institution: J. Craig Venter Institute. NIH institute: NIGMS.
Supports enhancements for the Celera Assembler shotgun fragment assembly software program, which is currently managed as an open source project via Sourceforge. The grant will enable the developers to us make the Celera Assembler "more user friendly, robust, capable of generating higher quality assemblies, and incorporating data from new types of sequencers," according to the grant abstract. "Towards this end, we will simplify and improve the algorithms and code, develop or incorporate analysis tools to assess the quality of assemblies, test the code on multiple computer platforms, debug the code on numerous organism assemblies, and develop a set of challenging benchmark assembly problems based on real data for use in rigorous regression testing to validate improved results using improved algorithms."
Dimensionality Reduction and Search for Analyzing Protein Structure. Start date: May 11, 2006. Expires: April 30, 2010. Amount: $183,439. Principal investigator: Lydia Kavraki. Institution: Rice University. NIH institute: NIGMS.
Supports a project to generate geometrically distinct low energy conformations of macromolecular complexes. The investigators will develop dimensionality reduction methods "that are tailored to complex molecular systems and can be used to represent such systems compactly," according to the grant abstract, adding that "the tight coupling of dimensionality reduction and efficient search algorithms will result in a method that can reason about large systems with some probabilistic guarantees, a presently elusive goal."
Statistical Methods for Identifying Genes Associated with Diabetes Development. Start date: June 1, 2006. Expires: May 31, 2008. Amount: $146,530. Principal investigator: Yinglei Lai. Institution: George Washington University. NIH institute: NIDDK.
Supports statistical analyses of microarray gene expression data sets in order to identify genes with differential expression associated with diabetes development. The statistical methods to be developed in the study will be validated through simulation studies and then applied to microarray gene expression data sets for diabetes studies and will be implemented in R-based computer programs that will be freely distributed to the scientific community.
Haplotype Analysis in Linkage Disequilibrium Mapping. Start date: July 1, 2006. Expires: June 30, 2011. Amount: $218,250. Principal investigator: Kui Zhang. Institution: University of Alabama at Birmingham. NIH institute: NIGMS.
Supports development of statistical and computational tools and methods to analyze haplotypes in linkage disequilibrium mapping of complex disease genes. Goals include developing efficient algorithms to estimate haplotype frequencies and determining haplotype configurations in general pedigrees for a large number of tightly linked genetic markers with recombinants, and defining new test statistics based on haplotype sharing for mapping genes responsible for complex human diseases.