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NIH Grants in Bioinformatics Awarded July 2005 — Sept. 2005

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Effect of Sequence Alignment Fidelity on Genome Research. Start date: July 1, 2005. Expires: June 30, 2007. Amount: $71,295. Principal investigator: Michael Rosenberg. Institution: Arizona State University. NIH institute: NLM.

Funds a pilot study to examine the feasibility of using computational sequence simulation to examine the effects and propagation of alignment error in high-throughput comparative and functional genomic sequence analysis. This study includes three aims: to profile the accuracy of DNA sequence alignment, including both paired- and multiple alignments; to define the factors that need to be included in a simulation of sequences in order to encompass a realistic level of biological complexity; and a case study to determine the effects of alignment error on the estimation of evolutionary distances among sequences.


A Biomedical Natural Language Processing Resource. Start date: July 1, 2005. Expires: June 30, 2009. Amount: $515,359. Principal investigator: Carol Friedman. Institution: Columbia University Health Sciences. NIH institute: NLM.

Proposal to establish a natural language processing (NLP) resource for the biomedical community. The foundation of the resource will be the MedLEE NLP system, which has been used for almost a decade in healthcare settings. The resource will also include a derivative of MedLEE called BioMedLEE, which encodes genotypic-phenotypic relations in the scientific literature.


An Integrated Framework of Epigenomics and Human Disease. Start date: July 6, 2005. Expires: May 31, 2010. Amount: $156,952. Principal investigator: Fatemeh Haghighi. Institution: Columbia University Health Sciences. NIH institute: NHGRI.

Proposal to develop statistical and computational tools that integrate bioinformatics, genetic epidemiology, and epigenetic models in order to study the etiological basis of complex diseases.


Machine vision analysis of C. elegans phenotypic patterns. Start date: July 15, 2005. Expires: May 31, 2010. Amount: $304,783. Principal investigator: William Schafer. Institution: University of California, San Diego. NIH institute: NIDA.

Proposal to develop computer vision tools for quantitatively characterizing the phenotypic patterns caused by mutations or pharmacological treatments in Caenorhabditis elegans. These tools are expected to be useful for correlating specific neurotransmission defects with characteristic behavioral patterns, and will also be used to generate a database containing behavioral data on a large set of mutant strains.


Software for Accurate Ligand-Protein Affinities. Start date: Aug. 1, 2005. Expires: July 31, 2006. Amount: $149,051. Principal investigator: Michael Potter. Institution: Verachem. NIH institute: NIGMS.

Project to develop and commercialize a new computational method for assessing the affinities of drug candidates for a protein target of known 3D structure, accounting efficiently for changes in translational, rotational and conformational entropy upon binding. During Phase I of the SBIR grant, the investigators aim to demonstrate successful initial implementation of the method on a single computer and in parallel on a commodity compute cluster, and to show that it yields converged free energies in nontrivial test cases.


The MEME suite of motif-based sequence analysis tools. Start date: Aug. 1, 2005. Expires: June 30, 2009. Amount: $301,855. Principal investigator: William Noble. Institution: University of Washington. NIH institute: NCRR.

Supports development of the MEME suite of bioinformatics tools, which includes MEME, a tool for identifying novel sequence patterns, and three other tools — Meta-MEME, MCAST and MAST — for searching sequence databases for matches to motif-based sequence models.


Computational Modeling /Design of Antimicrobial Peptides. Start date: Aug. 1, 2005. Expires: July 31, 2010. Amount: $236,124. Principal investigator: Yiannis Kaznessis. Institution: University of Minnesota, Twin Cities. NIH institute: NIGMS

Funds development of computational tools for antimicrobial peptide engineering. The investigators are developing data-mining algorithms that identify recurring sequence and structural patterns in known, naturally occurring antimicrobial peptides. Specific aims of the project include: quantifying the interactions between AMPs and mammalian, bacterial, and viral model membranes using high productivity computer simulations; recognizing the sequence/structural elements that are responsible for cathelicidin and minidefensin antimicrobial activity; and establishing a process of feedback mechanisms between experiments, computer models, and new experimental design in order to promote rational peptide engineering.


Integrative Meta-analysis of Microarray Data: Neuroscience. Start date: Aug. 1, 2005. Expires: July 31, 2010. Amount: $313,460. Principal investigator: Paul Pavlidis. Institution: Columbia University Health Sciences. NIH institute: NIGMS.

Supports development of an integrated gene expression informatics resource for neuroscience research. The investigators propose creating a facility that will allow neuroscientists to perform sophisticated computational analyses of large quantities of expression data coming from multiple laboratories. Data submitters will be able to control access to their data and the results coming from their data. The project will involve developing a database for meta-analysis of neuroscience-related gene expression data, tools for submission of data, and tools and algorithms for accessing the database and analyzing the data.


Biophysical Optimization of Oligonucleotide Microarrays. Start date: Aug. 1, 2005. Expires: July 31, 2010. Amount: $306,700. Principal investigator: Cynthia Gibas. Institution: University of North Carolina, Charlotte. NIH institute: NIGMS.

Supports development of a suite of software applications that incorporate experimentally validated solution hybridization parameters into the processes of microarray design and microarray data preprocessing. Given solution hybridization parameters, the investigators propose that they can accurately predict the binding behavior of perfectly matched and several classes of mismatched oligonucleotides on an array.


Microarray Data Standards and Supporting Applications. Start date: Aug. 23, 2005. Expires: July 31, 2008. Amount: $495,918. Principal investigator: Catherine Ball. Institution: Stanford University. NIH institute: NHGRI.

Funds activities of the Microarray Gene Expression Data Society (MGED) and development of MGED resources (MIAME, MAGE-ML, MAGE-stk and the MGED Ontology). Funds will support improvement of the MAGE Object Model, development of an advanced MAGE software toolkit, research on data quality metrics for microarray data, the extension of ontologies for describing microarray experiments, the development of tools for validating documents for MIAME compliance and MAGE formatting, and the development of freely available tools for sharing data.


Predicting Molecular Responses to ErbB Inhibitors. Start date: Sept. 1, 2005. Expires: Aug. 31, 2006. Amount: $107,931. Principal investigator: Ulrik Nielsen. Institution: Merrimack Pharmaceuticals. NIH institute: NCI.

Supports a network biology approach to identifying specific molecular patterns that can define and distinguish different cancers by their specific cue-signal-response (CSR) profile. First, an antibody microarray system will be used to simultaneously quantify cancer-relevant molecules (EGFR, ErbB2, ErbBS, ErbB4, EGF, heregulin, amphiregulin, betacellulin, and TGF-alpha), in addition to ERK and AKT. The investigators will then use computational methods to quantitatively predict the molecular signature response of the cancer cell to each specific cue. The result will be a highly predictive computational model, which based on the quantitative expression profile of the "cue", will predict ERK and AKT phosphorylation, and hence cellular response.


An Algorithm for Protein Switch Design. Start date: Sept. 1, 2005. Expires: Aug. 31, 2008. Amount: $42,068. Principal investigator: Xavier Ambroggio. Institution: University of North Carolina, Chapel Hill. NIH institute: NIGMS.

Proposal to improve protein-design algorithms to optimize the design of a sequence compatible with multiple structures dependent upon environmental context. A select group of proteins will be redesigned to switch structures and this behavior will be experimentally validated.


Computational Methods for Directed Functional Genomics. Start date: Sept. 1, 2005. Expires: Aug. 31, 2010. Amount: $400,000. Principal investigator: Frederick Roth. Institution: Harvard University Medical School. NIH institute: NHGRI.

Funds development of probabilistic scoring systems for computationally predicted gene function. The investigators will develop probabilistic models for predicting function and phenotype using Saccharomyces cerevisiae and Caenorhabditis elegans as model systems and will also develop computational methods to guide efficient discovery of genetic interactions in S. cerevisiae, as a model for guiding future high-throughput studies in metazoans.


BioHDF: Open Binary File Standards for Bioinformatics. Start date: Sept. 5, 2005. Expires: Feb. 28, 2006. Amount: $142,775. Principal investigator: Todd Smith. Institution: Geospiza. NIH institute: NHGRI.

Supports development of a bioinformatics software framework based on the National Center for Supercomputing Application's Hierarchical Data Format (HDF5). The proposed framework will integrate algorithms for DNA and protein sequence analysis. These algorithms will be either integrated into the system to directly read and write from HDF5 project files, or they will communicate with project files via filter programs that produce standardized XML formatted data.

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