Responding to Epidemic Threats Using Modern Bioinformatics Tools
Our goal for this project is to answer the urgent questions of how to deal with a “new” epidemic like SARS or Avian Flu: Are we equipped to rapidly identify and study new pathogens? Do we have the requisite analytical tools to classify the pathology of previously unknown biological agents? Do we have the detection technologies necessary to monitor our environments for biological threats and more importantly, how do we know if our tools are up to the task at hand?
Research groups in universities and governmental institutions have already developed many technologies for analyzing and classifying the behavior of pathogens. What is lacking, however, are the following:
- An efficient way to accumulate data for analysis and to integrate analytical tools rapidly under a unified framework (VALIS TOOLS).
- The statistical (informatics) methodology to evaluate the efficacy of existing tools, assays and sensor networks that are in the process of being developed (SIMPATHICA TOOLS)
- A database of experimental parameters, including genomic, proteomic and functional annotations that can be readily used for homeland security technology and research.
- A novel software tool called GOALIE (within SIMATHICA) to understand host-pathogen interactions
- A novel database system called CLARITY (also, within SIMATHICA) to understand the differences in host-pathogen interactions under varying strains of pathogens
- Interpretation of time-course gene-expression data to determine best manner of intervention against an invading pathogen
- A novel nano-cantilever based bio-sensor design
- An experimental set-up where the components of the sensors can be independently validated
- Collaboration with UCLA’s CNSI (California nano System Institute) to conduct the experiments
- Development of a mathematical model for probe hybridization and sensor bending dynamics of the cantilever
- Design of a simulator (first in Matlab and then in Simpathica) to validate the model and experiments.
- Design and implementation of an integrated “Sensor-Compiler”
- Design of a single molecule technology for rapid assay of pathogen genomes.
We have enhanced the capabilities of Simpathica to simulate nanotechnology-based simulation. We have published several journal and conference articles describing how the enhanced Simpathica-Valis toolset can accomplish rapid tool development and how they can be applied in practice.
We have completed a detailed analysis of host-pathogen interaction by analyzing the response of human kidney cells to staphylococcus enterotoxin B (SEB) with data collected by Walter-Reed Army Institute of Research. A paper summarizing this analysis is under preparation. We have recently designed a database schema to keep track of the results of these analyses for different strains of pathogen and use these data to understand the best responses to different strains.
The other main activities have been in designing a novel nano-biosensor and in setting up the experimental infrastructures to validate it. During the summer, with the help of a summer student, we plan to revise the code and the model completely in order to improve the accuracy of the prediction and revise our original design. In collaboration with the bench scientists at UCLA and NYU, we are conducting some simple tests and validation. We are also augmenting the proteomic assay with single molecule genomic assay in order to determine minute amount of pathogenic DNA. We have initiated several simple experiments involving viral materials (e.g., adeno and lambda) to determine if they can be detected in minute amounts using LNA and PNA probes.
- "Simpathica: A Computational Systems Biology Tool within the Valis Bioinformatics Environment," (M. Antoniotti, S. Paxia, N. Ugel, and B. Mishra), Computational Systems Biology, (Ed. E. Eiles and A. Kriete), Elsevier, 2005.
- "Reconstructing Formal Temporal Models of Cellular Events using the GO Process Ontology," (M. Antoniotti, N. Ramakrishnan, and B. Mishra), Proceedings of the Eighth Annual Bio-Ontologies Meeting, (ISMB'05 Satellite Workshop), Detroit, MI, June 23-24 2005.
- "GOALIE, A Common Lisp Application to Discover Kripke Models: Redescribing Biological Processes from Time-Course Data," (M. Antoniotti, N. Ramakrishnan, and B. mishra), International Lisp Conference, ILC 2005, Stanford University, June 19-22, 2005.
- "Multiple Biological Model Classification: From System Biology to Synthetic Biology," (M. Antoniotti et al.), BioConcur'04, 2nd Workshop on Concurrent Models in Molecular Biology, The Royal Society, London, Transactions on Computational Systems Biology, 2005.
- "Remembrance of Experiments Past: A Redescription Based Tool for Discovery in Complex Systems," (S. Kleinberg, M. Antoniotti, S. Tadepalli, N. Ramakrishnan, and B. Mishra), Interational Conference on Complex Systems, Quincy, Boston, MA, June 2006.
- "Single Molecule DNA Profiling," (J. Reed, B.Mishra and J.K. Gimzewski), 2006.
- "Methods, Systems and Software Arrangement for Reconstructing Formal Descriptive Models of Processes from Functional/Modal Data using Suitable Ontology (GOALIE)," Inventors: M. Antoniotti, N. Ramakrishnan and B. Mishra, 2005.
- "Methods, Systems and Software arrangements for Organization of Multiple sets of Data," Inventors: S. Kleinberg and B.Mishra, 2006.