Genetic roadmap charts links between drugs and human disease

September 2017

Pharmaceutical News

Country of origin: USA

A research team led by scientists at the Broad Institute of MIT and Harvard has developed a new kind of genetic ?roadmap? that can connect human diseases with potential drugs to treat them, as well as predict how new drugs work in human cells.

Based on these initial results, the researchers propose a public project to expand the Connectivity Map - in the spirit of the Human Genome Project - to accelerate the search for new drugs to treat disease.

?The Connectivity Map works much like a Google search to discover connections among drugs and diseases,? said Todd Golub, the director of the Broad Institute?s cancer programme, an investigator at the Dana-Farber Cancer Institute, an Associate professor of paediatrics at Harvard Medical School, and an investigator at the Howard Hughes Medical Institute. ?These connections are notoriously difficult to find, in part because drugs and diseases are characterised in completely different scientific languages.?

A key challenge in biomedicine is to connect each human disease with drugs that effectively treat it while understanding the molecular basis for the drugs? effects.
To solve this problem systematically, the scientists described the effects of drugs and diseases in the common language of ?genomic signatures,? meaning the full complement of genes that the drugs turn on and off.

To create a first-generation Connectivity Map, the scientists measured the genomic signatures of more than 160 drugs and other biologically active compounds. They next developed a computer programme to compare the signatures of the drugs with each other and also with the signatures seen in diseases. In this way they were able to discover the mechanisms underlying a novel drug candidate for prostate cancer, and that a drug currently used to treat one disease may be useful in another.

Like other scientific databases, the true value of the Connectivity Map lies in its capacity to be queried by nearly any researcher with a computer. The genomic signature of a particular disease, drug or other aspect of human biology serves as the search ?word.? Potential functional connections are revealed through a rank-ordered list of reference compounds in the database that have matching signatures.

Data from this work are publicly available online.

A web-based tool for scientists to perform their own analyses using the Connectivity Map is also freely available.

N.B. AT THE TIME OF REPORTING, REGISTRATION TO THIS RESOURCE IS FREE.

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