ABTERRA BIOSCIENCES, INC. — Department of Health and Human Services SBIR Phase I: 400

Description

Project Summary Advances in genome miningand consequent realization of untapped microbial diversity has lead to renewed interest in natural productNPdiscoveryNPs are a rich source of therapeutic candidateswith a long history of successes in combating infectious diseasesand oncologyThe emergence of antibiotic resistant bacteria like Cdifficile and carbapenem resistant enterobacteiaceaeCREonly emphasizes the desperateand growing need for new therapeuticsInvestigation of microenvironments for novel NP compounds is labor intensiveand requires numerous molecular biologyand biochemical techniques to isolate and characterize novel NP compoundsIn additionmonths of effort to isolate and identify a compound can be wasted if the compound was previously discoveredHigh throughput methods are needed to quickly identify drug leads from a samplewith minimal upfront investmentTandem mass spectrometryMSis a high throughput technology capable of sensitively identifying moleculesUnlike nuclear magnetic resonance spectroscopywhich is a widely used in NP research for structure elucidation and dereplicationtandem MS can be used to analyze small amounts of compounds directly from the environmental extractWhile MS offers the hope of rapid NP identificationof spectra cannot be matched to existing spectral librariesQuorum is a computational platform that organizes tandem MS data into molecular networksMolecular networks connect related compounds that differ by a mutationmodificationor adductQuorum aims to increase NP compound annotations compared to previous approaches by integrating spectral library search and structure database searchIn additionannotations of known compounds can be automatically propagated to relatedbut unknown compounds via similarity of their tandem mass spectraQuorum will be deployed as a web application to enable interactive visual interrogation of the network topology and underlying data analysisGiven the design of a MS experimente gcase versus control or time seriesthe application will perform statistical analysis to highlight significantly enriched compounds and sub networksThese features can be used to quickly identify novel drug leads or to optimize growth and extraction protocols While natural products and their derivatives compriseof FDA recently approved drugsnew discoveries by pharmaceutical companies has waned due to the difficulty in isolating novel compounds and lack of high throughput methods for characterizationQuorum is a software tool that analyzes mass spectrometry data to characterize compounds from microbe rich extractsas well as track compound behavior across samples or conditionsThe innovative molecular networking approach employed by Quorum will dramatically increase the rate for identifying compounds and accelerate discovery of new therapeutics