Molecular Mechanisms Sensitive to Chemical Exposures Identified

University of Massachusetts Amherst researchers used data on 591,084 unique chemical-gene interactions to identify genes and molecular pathways most sensitive to chemical exposures. According to the study, published in Chemosphere, almost every well-known molecular pathway is sensitive to chemicals to a certain degree.

The study identified genes and molecular pathways most sensitive to chemical exposures, including mechanisms involving aging, lipid metabolism, and autoimmune disease. "These findings for the first time prove that current epidemics in metabolic and autoimmune disorders may be partly due to a very broad range of chemical exposures," explains Alexander Suvorov, lead author of the paper.

To carry out their analysis, the team extracted data on chemical-gene interactions from the Comparative Toxicogenomics Database. They then created a database of 591,084 chemical-gene interactions reported in 2,169 studies that used high-throughput gene expression analysis.

"In the recent past, everything that we knew about molecular mechanisms affected by chemicals was coming from low-throughput experiments," Suvorov says. "I wanted to find some approach that would tell us in a completely unbiased way which mechanisms are sensitive and which are not. I wondered if we were missing a significant toxic response just because no one ever looked for it," Suvorov says. "By overlaying many high-throughput studies, we can see changes in the expression of all genes all at once. And that is unbiased because we are not cherry-picking any particular molecular mechanisms."

The interactions analyzed encompassed 17,338 unique genes and 1,239 unique chemicals. The researchers split their database of chemicals into two parts—pharmaceutical chemicals and other chemicals such as industrial, agricultural, cosmetics and pollutants. When the sensitivity of genes to pharmaceutical chemicals was compared to the sensitivity of genes to the other chemicals, the results were the same. "That proves that when analysis is done on really big numbers of chemicals, their composition does not matter," Suvorov says.

"This study represents a significant step forward in the use of genomic data for the improvement of public health policies and decisions," Suvorov adds, "and the public health field will benefit from a future focus of toxicological research on these identified sensitive mechanisms."