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Using the human genome sequence to discover unknown pathogens
Edward R. Winstead


Scientists have developed a novel strategy for identifying microbes that live in the human body and may cause infectious disease. In the strategy, researchers take genetic code derived from human tissue and compare it to the draft human genome sequence. DNA sequences that are present in the tissue samples but not the human genome may belong to microbes.

Detail of schematic of computational subtraction. View larger

The human body is home to bacteria, viruses, and fungi, many of which perform beneficial tasks. To investigate infectious disease in humans, researchers need to distinguish between DNA from harmless and pathogenic organisms. Thus, the new method first identifies foreign DNA and then screens these data against all the known microbial DNA sequences.

In theory, the strategy can detect DNA from pathogens no one has ever seen. Matthew Meyerson, of the Dana-Farber Cancer Institute in Boston, Massachusetts, led the research. The method, known as computational subtraction, is reported in Nature Genetics.

As a test case, Meyerson's team analyzed 3.2 million partial gene sequences derived from healthy and diseased human tissue. From these data, sequences found in the human genome were subtracted out, leaving about two percent of the total. As expected, these sequences included DNA from viruses known to have infected certain tissue samples.

Meyerson suspects that a number of puzzling human diseases will turn out to involve microbial infections. His laboratory plans to use the method to investigate the causes of chronic diseases like rheumatoid arthritis, multiple sclerosis, as well as several types of cancer.

The category of infectious diseases in humans has grown in recent years. For example, it is now known that certain stomach and duodenal ulcers, which for decades were blamed on stress and diet, are caused by the bacterium Helicobacter pylori.

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Weber, G. et al. Identification of foreign gene sequences by transcript filtering against the human genome. Nat Genet. Published online January 15, 2002.

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