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Funding Update: Aug 20, 2010


NSF Bioinformatics Grants Awarded July 23 — Aug. 19, 2010

Undergraduate Research in Computational Biology at UC Merced
Start date: Jan. 1, 2011
Expires: Dec. 31, 2015
Awarded amount to date: $994,999
Principal investigator: Masakatsu Watanabe
Sponsor: University of California, Merced

Supports an undergraduate research and mentoring program to educate students about computational and mathematical biology methods and tools. The program, which will begin in spring 2011 and continue through fall 2015, will include four cohorts of five to six students who will first receive classroom and hands-on training and then join research projects with faculty mentors in the UC Merced Biological Sciences, Applied Mathematics, and Computer Science programs.

Next Generation DNA Sequencing: Signal Processing Perspectives
Start date: Sept. 1, 2010
Expires: Aug. 31, 2011
Awarded amount to date: $122,542
Principal investigator: Haris Vikalo
Sponsor: University of Texas at Austin

The grant abstract notes that although sequencing-by-synthesis is two orders of magnitude cheaper than conventional sequencing, "fidelity and sequence read-lengths of sequencing-by-synthesis are inferior to those of the costly conventional technology, and its overall performance is insufficient for most medical studies." In response, the grantees intend to develop signal-processing techniques that will enable accurate and reliable DNA sequence detection in sequencing-by-synthesis systems. The investigator aims to first develop mathematical models of the sequencing-by-synthesis process and then design computationally efficient algorithms for optimal DNA sequence detection in sequencing-by-synthesis systems.

Prototyping GenoTHREAT: a Biosecurity Solution for Synthetic Genomics
Start date: Sept. 1, 2010
Expires: Aug. 31, 2011 (Estimated)
Awarded amount to date: $99,819
Principal investigator: Jean Peccoud
Sponsor: Virginia Polytechnic Institute and State University

Supports development of GenoTHREAT, software to screen DNA sequences ordered from gene synthesis companies for the possible presence of potentially harmful sequences. The software is based on a screening algorithm recommended by the Department of Health and Human Services in a document entitled "Screening Frameworks Guidance for Synthetic Double-Stranded DNA Providers," and is applied to a database of publicly available synthetic DNA sequences and annotated test cases. (See BioInform's coverage of GenoTHREAT here.)

Algorithms for Tandem Repeat Variant Discovery Using Next Generation Sequencing Data
Start date: Aug. 15, 2010
Expires: July 31, 2011
Awarded amount to date: $162,034
Principal investigator: Gary Benson
Sponsor: Trustees of Boston University

"Current sequencing projects are producing many billions of reads rich in [tandem repeat] variant information. Yet, current read mapping algorithms, which attempt to assign each read to its proper location on the reference genome, are not designed to detect TR variants," according to the grant abstract. The investigators aim to address this issue by developing new algorithms and strategies "to accurately and efficiently map TR-containing reads to reference genome TR loci." Anticipated algorithmic developments include the optimization of tree-based alignment methods; the production of space-saving, Burrows Wheeler transforms of the most redundant tree parts; the development of a Four-Russians style block computation for edit distance alignment in the trees; and the development of a bounding computation for edit-distance.

Overlapping Clustering Analysis of Biological Networks
Start date: Aug. 15, 2010
Expires: July 31, 2011
Awarded amount to date: $158,312
Principal investigator: Aidong Zhang
Sponsor: State University of New York at Buffalo

Funds the development of an approach to detect overlapping clusters in protein-protein interaction data based on a method that integrates domain knowledge with the protein interaction data so that the data will be more reliable. Further information about the project is available here.

Advanced Grid-Enabled Algorithms for Discovering Protein Conformations
Start date: Aug. 15, 2010
Expires: July 31, 2013 (Estimated)
Awarded amount to date: $449,999
Principal investigator: Jesus Izaguirre
Sponsor: University of Notre Dame

Supports the development of new algorithms and software to discover the conformation of proteins. The investigators will use a dimensionality-reduction approach in which the search "is confined to the slowest and most collective motions of the protein," according to the grant abstract. "This greatly accelerates sampling and is scalable to large proteins."

Molecular-Level Stochastic Simulation To Predict The Dynamics of Protein Misfolding and Aggregation
Start date: Aug. 15, 2010
Expires: July 31, 2012
Awarded amount to date: $125,000
Principal investigator: Preetam Ghosh
Sponsor: University of Southern Mississippi

The investigators will use the amyloid-beta peptide, which is known to form misfolded aggregates, in order to establish a framework for stochastic molecular-level simulation of the fibril formation process, which "will serve as a basis for analyzing more realistic models with competing pathways to precisely predict the dynamics and mechanisms of protein aggregation," according to the grant abstract.

Algorithmic Approaches for Pathway and Gene Group Analysis in Genetic Studies
Start date: Aug. 15, 2010
Expires: July 31, 2013 (Estimated)
Awarded amount to date: $500,000
Principal investigator: Benjamin Raphael
Sponsor: Brown University

Supports a project to develop algorithmic and statistical techniques for four challenges in analyzing DNA sequence variants: incorporating prior knowledge of gene interactions; deriving robust statistical tests to overcome multiple hypothesis-testing problems in network analysis; performing de novo identification of gene groups without an interaction network; and implementation of algorithms for evaluation of somatic mutations identified in cancer genome sequencing studies and rare genetic variants in human association studies.

Novel Tools for the Analysis & Interpretation of Gene Signaling Pathways
Start date: Aug. 1, 2010
Expires: July 31, 2011
Awarded amount to date: $500,200
Principal investigator: Sorin Draghici
Sponsor: Wayne State University

Funds development of new algorithms and methods for analyzing gene signaling pathways. "Using a systems biology approach, the project will perform an impact analysis that includes classic performance statistics but also considers other crucial factors that have been previously neglected, such as the magnitude of each gene's expression change, their significance, their position in the given pathways, their interactions, and the full topology of the pathway," the grant abstract states. "Preliminary work shows that the classical analysis can produce both false positives and false negatives while the proposed impact analysis can provide biologically meaningful results."

Computational Tools and Statistical Analysis of Co-Varying Rates of Different Mutation Types
Start date: Aug. 1, 2010
Expires: July 31, 2013
Awarded amount to date: $578,036
Principal investigator: Kateryna Makova
Sponsor: Pennsylvania State University, University Park

Funds a project that will study regional variation and co-variation rates in completely sequenced mammalian genomes and human re-sequencing data. The findings on mutation rates and co-occurrence "will be used to improve computational predictions of functional regions by means of background corrections exploiting several mutation types simultaneously," according to the grant abstract. Computational and statistical tools developed in this project will be implemented in the Galaxy genome analysis platform.

A Computational Approach to Template-based Structure Selection for Protein-Protein Interactions
Start date: Aug. 1, 2010
Expires: July 31, 2011
Awarded amount to date: $131,891
Principal investigator: Xiaoqin Zou
Sponsor: University of Missouri-Columbia

Supports a project that aims to improve the prediction of protein-protein interactions. Specifically, the investigators will develop a new, "rigorously derived" scoring function for protein-protein interactions based on physical principles. "A new paradigm will also be developed and validated for predicting protein-protein interactions for cases in which only homology-modeled structures are available," the abstract states. Software and test sets generated in the project will be available here.

Algorithmic Foundations of Phylogenetic Tree Reconciliation
Start date: Aug. 1, 2010
Expires: July 31, 2011
Awarded amount to date: $100,000
Principal investigator: David Fernandez-Baca
Sponsor: Iowa State University

This project will address "the fundamental algorithmic problems that arise in reconciling multiple conflicting phylogenetic trees into a single supertree that represents them all," the grant abstract states. "The reconciliation problem will be treated as one of finding a supertree whose total dissimilarity with the input trees is minimum."

The Scan

Study Tracks Off-Target Gene Edits Linked to Epigenetic Features

Using machine learning, researchers characterize in BMC Genomics the potential off-target effects of 19 computed or experimentally determined epigenetic features during CRISPR-Cas9 editing.

Coronary Artery Disease Risk Loci, Candidate Genes Identified in GWAS Meta-Analysis

A GWAS in Nature Genetics of nearly 1.4 million coronary artery disease cases and controls focused in on more than 200 candidate causal genes, including the cell motility-related myosin gene MYO9B.

Multiple Sclerosis Contributors Found in Proteome-Wide Association Study

With a combination of genome-wide association and brain proteome data, researchers in the Annals of Clinical and Translational Neurology tracked down dozens of potential multiple sclerosis risk proteins.

Quality Improvement Study Compares Molecular Tumor Boards, Central Consensus Recommendations

With 50 simulated cancer cases, researchers in JAMA Network Open compared molecular tumor board recommendations with central consensus plans at a dozen centers in Japan.