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NIH Grants in Bioinformatics Awarded Dec. 2005 -- Feb. 2005

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Modeling Gene Networks in Neuronal Adaptation to Alcohol. Start date: Dec. 10, 2005. Expires: Nov. 30, 2009. FY 2006 amount: $351,000. Principal investigator: James Schwaber. Institution: Thomas Jefferson University. NIH institute: NIAAA.

Supports a study that will collect a time series of global gene expression datasets related to alcohol withdrawal of neurons in order to model the gene networks and cellular controls of alcohol withdrawal in the brain. The grantees will develop statistical models of the patterns of transcriptional response during acute alcohol withdrawal across time as compared to the chronic alcohol state and the normal state and within two key neuronal populations, and will identify evolving gene regulatory network activities and mechanisms.


The Ciona savignyi Genetic Map. Start date: Jan. 1, 2006. Expires: Dec. 31, 2008. FY 2006 amount: $219,456. Principal investigator: Arend Sidow. Institution: Stanford University. NIH institute: NIGMS.

Proposal to construct a 300-marker linkage map for Ciona savignyi that is fully integrated with what will become the annotated high-quality genome reference sequence. In addition to the genome-wide map, high-resolution fine-scale mapping in regions of uncertain sequence assembly will be performed to resolve ambiguities in the C. savignyi genome reference sequence. The map, along with a database of "thousands of potentially polymorphic markers distributed across the genome," will be made publicly available, according to the grant abstract.


Integrative Analysis of Cross-Platform Microarray Data. Start date: Jan. 1, 2006. Expires: Dec. 31, 2010. FY 2006 amount: $150,869. Institution: University of Southern California. Principal investigator: Xianghong Jasmine Zhou. NIH institute: NIGMS.

Proposal to develop computational and statistical methods to integrate cross-platform microarray data. Goals include detecting recurrent expression patterns across many microarray datasets; performing functional and transcriptional annotation for multiple genomes; predicting transcription regulators for higher eukaryotic genes without prior information on protein-DNA binding sites; and identifying genetic networks that are signatures of diseases. The developed methods will be released in the form of a software package called ArrayMine.


BioPAX — Biological Pathway Community Workshop. Start date: Jan. 10, 2006. Expires: Dec. 31, 2008. FY 2006 amount: $10,000. Principal investigator: Chris Sander. Institution: Sloan-Kettering Institute for Cancer Research. NIH institute: NIGMS.

Supports a meeting series for the BioPAX biological pathway standards consortium for the years 2006, 2007, and 2008. The goals of the meeting series are to "expand the BioPAX data model by adding support for signaling pathways, gene regulation networks and genetic interactions, such as epistasis; to increase database and tool support for.BioPAX; and to encourage the growth of publicly accessible pathway data and its application to biological problems," according to the grant abstract.


Assessment of Protein Flexibility in Molecular Docking. Start date: Jan. 16, 2006. Expires: Jan. 15, 2009. FY 2006 amount: $45,976. Principal investigator: Roger Armen. Institution: Scripps Research Institute. NIH institute: NIGMS.

Supports development of a new docking algorithm that directly incorporates protein flexibility into the docking procedure with torsion angle dynamics. For a test set of 12 proteins, several conformational sampling techniques will be used to generate representative protein ensembles for molecular docking. The results of rigid docking into multiple crystal structures will be compared against rigid docking into generated protein ensembles. These results will be used to develop the new algorithm.


A Core Database of Interacting Proteins (DIP). Start date: Feb. 1, 2006. Expires: Jan. 31, 2010. FY 2006 amount: $439,479. Principal investigator: David Eisenberg. Institution: University of California, Los Angeles. NIH institute: NIGMS.

Supports expansion of the Database of Interacting Proteins (DIP), a database of information on interacting proteins. According to the grantees, DIP will adopt "a procedure of direct deposition of experimental data by primary authors." Therefore, methods for the assessment of data quality will be extended and applied to DIP, in order to define a core set of "highly reliable" interaction data. The core interactions will permit construction of networks of interacting proteins, useful to cell and systems biologists. DIP's IT infrastructure will also be upgraded.


Decoding Gene Expression Control Using Conditional Clustering by Dynamics. Start date: Feb. 3, 2006. Expires: Jan. 31, 2009. FY 2006 amount: $325,000. Principal investigator: Marco Ramoni. Institution: Children's Hospital Boston. NIH institute: NHGRI.

Proposal to develop an unsupervised approach and an integrated software environment to automatically discover regulatory mechanisms from temporal microarray experiments. The grantees plan to develop a framework that will be used to specify and answer design questions of sample size and sampling frequency determination. Based upon this framework, the investigators intend to develop a model-based approach and an iterative search algorithm, called Conditional Clustering, to identify "different patterns of behavior determined by a set of genes through the analysis of the behavior of a gene given a set of other genes, rather than the behavior of each gene in isolation," according to the grant abstract.


Bioinformatics Tools for Multi-Center Diagnostic Trials. Start date: Feb. 7, 2006. Expires: Jan. 31, 2009. FY 2006 amount: $221,207. Principal investigator: Kelly Zou. Institution: Brigham and Women's Hospital. NIH institute: NIGMS.

Proposal to develop a general statistical validation strategy for evaluating multi-center diagnostic imaging trial data. The short-term goal of the project is to develop informatics tools to validate diagnostic systems such as breast cancer mammography and functional magnetic resonance imaging. The long-term goal is to develop efficient ways for better analyzing clustered data and utilizing prior knowledge in multi-center clinical trials, according to the grant abstract.


Individual Cell Motility Image Informatics. Start date: Feb. 10, 2006. Expires: Aug. 9, 2006. FY 2006 amount: $100,000. Principal investigator: Shih-Jong Lee. Institution: SVision. NIH institute: NIGMS.

Phase I SBIR funds development of a next-generation microscopy image informatics tool called SVCell that will include improved cell recognition, measurement, and analysis technology for a broad range of cell types in fixed-point assays. SVision intends to make SVCell Motility available as part of a suite of open platform image informatics applications.


Database for Modified Nucleotides, Fluorophors and Additives. Start date: Feb. 15, 2006. Expires: Aug. 14, 2006. FY 2006 amount: $120,017. Principal investigator: Svetlana Morosyuk. Institution: DNA Software. NIH institute: NIGMS.

Funds further development of DNA Software's Oligonucleotide Modeling Platform (OMP) to add the capability to design probes and primers that contain modified nucleotides, fluorophore labels, and hybridize in the presence of buffer additives.


Predicting and analyzing protein interaction networks. Start date: Feb. 18, 2006. Expires: Jan. 31, 2011. FY 2006 amount: $266,069. Principal investigator: Mona Singh. Institution: Princeton University. NIH institute: NIGMS.

Supports the development of algorithms for analyzing and predicting protein interaction maps. Project goals include developing algorithms that exploit the topology of whole-genome protein interaction maps and the relationships between protein functions; building a system for interrogating protein interaction networks using templates specifying common patterns of interactions or pathways; and developing a general structural bioinformatics approach for leveraging properties of specific protein interaction interfaces.


A New Approach to Rapid Protein-Protein Docking. Start date: March 1, 2006. Expires: Feb. 28, 2009. FY 2006 amount: $436,054. Principal investigator: Chandrajit Bajaj. Institution: University of Texas, Austin. NIH institute: NIGMS.

Funds a collaboration between structural molecular biologists, applied mathematicians, and computer scientists to develop and optimize algorithms and integrate them into a flexible docking-workflow environment. The proposed framework is expected to be applicable to a wide range of biological systems, extensible, and efficient with respect to space and time. The system will score protein-protein interactions based on analytic docking affinity functions defined on molecular interface volumes.


Automated Distant Homology Modeling Meta-server. Start date: March 1, 2006. Expires: Feb. 28, 2010. FY 2006 amount: $260,733. Principal investigator: Daniel Fischer. Institution: State University of New York at Buffalo. NIH institute: NIGMS.

Proposal to create a protein structure prediction meta-server for close and distant homology modeling. Specific aims include evaluating the performance of current fold-recognition methods in order to identify the most accurate ones; developing improved algorithms to generate more accurate fold-recognition hybrid models and alignments; and applying the meta-server to specific problems of biological interest. The long term goal is to "create a meta-server that will become a standard and will revolutionize the protein structure prediction field in an analogous way to the revolution that PSI-Blast brought about in the sequence-comparison field, a few years ago," according to the grant abstract.

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