Yeasts Provide Clues to Different Drug Responses

What are the genetic and environmental factors relating to drug reactions? How do these predict how a drug will affect us?

A major article in Science this week from researchers at the University of British Columbia exposed 6,000 strains of yeast to 3,000 drugs. Using yeast response data from the project, researchers found that the yeast cells reacted in 50 different main ways to the vast array of drugs.

Gene signatures predict drug response
These 50 major response types, known as gene signatures, are like fingerprints that identify all genes and their relevance to a specific drug treatment. Using genomics, proteomics and bioinformatics platforms, these networks were used to extrapolate the likely effects of related chemicals, their impact upon genetic pathways, and to identify putative gene functions.

Predictive medicine is a possible outcome of this discovery, given the relatively small number of gene signatures, using a person's genome to predict their drug response. The identification of better, more effective therapies for each of the gene signature could also be made easier.

Drug response reference map
"This is a starting reference map for understanding variation in drug response," says Guri Giaever, an associate professor in UBC's Faculty of Pharmaceutical Sciences, and a senior author on the study, published today in Science. "It won't be easy but our results suggest it is a solvable problem."
Corey Nislow, also associate professor in the faculty and senior author, says this research will help us better understand how and why some drugs work and others don't.

Of greatest interest is the relevance to cancer treatment. Researchers identified all genes that are essential for growth when cells are chemically stressed. Because cancer is principally a cell that grows out of control, the research points to different strategies to develop new drugs that target these genes.

Mapping the Cellular Response to Small Molecules Using Chemogenomic Fitness Signatures. Science, 2014; 344 (6180): 208.