Bioinformatics for Immune Response Biosignature Analyses

DESCRIPTION (provided by applicant): Our Fast Track Phase I objective is to define and prototype a new computational (bioinformatic) framework for innate immune response biosignature analyses of infectious diseases including biowarfare agents. The framework combines Dynamic Bayesian Network learning and modeling techniques with "Intelligent Software Agent" (ISA) technology to enable quantitative and qualitative analysis of over 100 time-course simultaneously measured biomarkers (biosignatures). We believe that infectious agents produce unique temporal biosignatures that can be observed by simultaneously measuring multiple circulating molecular biomarkers (cytokines, chemokines and others TBD) that are integral to the host's innate immune and inflammatory response mechanisms. A new computational methodology is essential for decoding molecular responses and the associated complexities of interacting processes that uniquely model and identify an infectious agent. Our methodology analyzes temporal patterns of change of circulating proteins during the initial onset of infection and its progression to reveal unique proteome-level "biosignatures." This new framework will substantially advance the industry's capability to analyze complex simultaneous protein interactions and time-course investigations of diseases at the proteomic level and not just for circulating proteins. Our Phase I milestone is to develop a prototype framework and demonstrate its concept and feasibility. We will refine our framework and continue development under Phase II efforts and validate our framework using in vivo mice models challenged by infectious agents. In Phase II, we will be integrating our platform to communicate with the Luminex LapMAP microbead flow cytometry immunoassay instrument. This instrument can measure up to 100 different cytokines/proteins/SNPs, simultaneously from a serum sample < 50 microliters. This is the core technology for Seralogix's web based point-of-care platform under commercial development being leveraged as in-kind contribution for this proposal. Our long-term objective is to commercialize a proteomics-based point-of-care diagnostics platform for the presymptomatic detection of human infectious diseases, including BWAs. We envision the platform will have dual-use applications to supped the front-line physicians' therapeutics and diagnosis of emergent and bioterrorism infectious agents that are of great concern to public health and homeland security. The platform is intended to enable a National Counter-Bioterrorism Defense Platform critical to the Nation's preparedness against terrorist threats. The criticality of pre-symptomatic detection of any person suspected of BWA infection is obvious, not only for his or her own immediate treatment but also for the avoidance of a catastrophic national health disaster. A unique multidisciplinary team of industry and academia has been assembled for Phase I and Phase II.