Genomics-based Approaches to New Pathogen Discovery in Chronic Human Diseases
Team Leader:
Donald E. Ganem, M.D., Howard Hughes Medical Institute/ University of California, San Francisco
Key Investigators:
Joseph R. DeRisi, Ph.D., University of California, San Francisco; Homer A. Boushey, M.D., University of California, San Francisco
Team Disciplines:
Virology, Infectious Diseases, Genomics/ Informatics, Pulmonology
Abstract
In the past 2 decades, great strides have been made in identifying infectious agents that cause human disease. Particularly important has been the recognition that many chronic diseases once thought to be genetic, metabolic or degenerative in origin are in fact precipitated by infection. (Examples: peptic ulcer disease, Lyme arthritis and cervical cancer). Suspicion is now growing that other disease processes - chronic inflammatory states, autoimmune diseases, and some degenerative disorders - may likewise have infectious precipitants or cofactors. However, our ability to identify new pathogens has been strongly impaired by the inadequacy of currently available techniques for identifying infectious agents. The emerging science of genomics provides new opportunities to advance this area of research. Rather than attempting to identify new pathogens by their growth properties in culture, genomic methods allow pathogens to be sought by directly attempting to detect their DNA in a clinical specimen. We have developed a new, genomics-based method for the detection of viral genomes in such specimens, using DNA microarrays bearing the conserved sequences of all known viruses. Several short fragments of DNA from each known virus are deposited on a glass slide; the DNA or RNA from the patient sample is biochemically labelled and then tested for its ability to recognize the spots of known viral DNA that are on this lside. The subsequent pattern of reactions is analyzed by computer to yield the identity of the pathogen present in the sample. In this way, in a single test we can search for nearly 1000 known viruses; in addition, the test has the potential to identify new viruses that are only partially related to presently known agents. Using this test, we are searching for new agents implicated in asthma, pneumonitis, hepatitis and other chronic diseases.