Abstract
BackgroundMethods of weakening and attenuating pathogens’ abilities to infect and propagate in a host, thus allowing the natural immune system to more easily decimate invaders, have gained attention as alternatives to broad-spectrum targeting approaches. The following work describes a technique to identifying proteins involved in virulence by relying on latent information computationally gathered across biological repositories, applicable to both generic and specific virulence categories.ResultsA lightweight method for data integration is used, which links information regarding a protein via a path-based query graph. A method of weighting is then applied to query graphs that can serve as input to various statistical classification methods for discrimination, and the combined usage of both data integration and learning methods are tested against the problem of both generalized and specific virulence function prediction.ConclusionsThis approach improves coverage of functional data over a protein. Moreover, while depending largely on noisy and potentially non-curated data from public sources, we find it outperforms other techniques to identification of general virulence factors and baseline remote homology detection methods for specific virulence categories.
Highlights
Methods of weakening and attenuating pathogens’ abilities to infect and propagate in a host, allowing the natural immune system to more decimate invaders, have gained attention as alternatives to broad-spectrum targeting approaches
Though recent decades have seen a decrease in mortality related to infectious disease, new dangers have appeared in the form of emerging and re-emerging pathogens as well as the continuing threat of weaponized infectious agents [1,2], creating a strong need to find new methods and targets for treatment
We extend the notion of a query graph to exploratory query graphs, or a query graphs expanded to the limit of connections defined in S such that for any given protein query, all possible connections between records and all records are realized
Summary
Methods of weakening and attenuating pathogens’ abilities to infect and propagate in a host, allowing the natural immune system to more decimate invaders, have gained attention as alternatives to broad-spectrum targeting approaches. Though recent decades have seen a decrease in mortality related to infectious disease, new dangers have appeared in the form of emerging and re-emerging pathogens as well as the continuing threat of weaponized infectious agents [1,2], creating a strong need to find new methods and targets for treatment. Underscoring the importance of this issue, the National Institute of Allergy and Infectious Disease maintains a categorical ranking of disease-causing microorganisms (NIAID Biodefense Categories) that could cause significant harm and mortality [3]. Many pathogen genomes have been sequenced and continue to be sequenced, and hold the promise of expediting new therapeutics. Genomic and proteomic sequences are available for many bacterial and viral causes of disease. The National Microbial Pathogen Data Resource (NMPDR), a curated
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