MIT Scientists Create Map of Human Epigenome

mit professor manolis kellis led the effort to map the human epigenome. photo by M. Scott Brauer.

Since the mapping of the human genome more than a decade ago, scientists have made significant progress in their understanding of the links between genetics and disease. Now, new research from the NIH’s Roadmap Epigenomic Consortium may boost those advances even further.

In a new study recently published in the journal Nature, researchers presented their newly created map of the human epigenome—the set of chemical modifications to DNA that enables cells in the body to perform different functions. The study, which analyzed more than 100 reference epigenomes, is “the most comprehensive view of the human epigenome to date,” according to an MIT report.

Manolis Kellis, a computer science professor at MIT and the study’s corresponding author, says that it’s helpful to conceptualize the relationship between the genome and epigenome in this way: If the genome is “the book of life,” he says, the epigenome is the collection of Post-it notes and highlighted passages that tells the cells in the body—all 37 trillion—what information is important for functionality and gene regulation. By understanding the “circuitry” of the cells, Kellis says that researchers can gain crucial insight on where genetic variants that predispose humans to various diseases such as Alzheimer’s are active in the body. This insight is important because it can help scientists develop new treatments and therapeutics against disease, he says.

“That’s what genomics is all about,” Kellis says. “It’s not about saying, ‘Too bad. You’re going to get the disease.’ It’s about intervening and saying, ‘Here’s what I can do about it.'”

Taking into consideration that each person’s epigenome is unique, researchers created the reference map by generating thousands of data sets that represent the diversity of human biology. Kellis says that mapping the epigenome gave researchers the opportunity to look at all the genetic variants that have been identified to date and pinpoint where the variants are active in the body. According to the MIT report:

The researchers found significant tissue-specific enhancer signatures for genetic variants associated with 58 different traits. These included height, in embryonic stem cells; multiple sclerosis, in immune cells; attention deficit disorder, in brain tissues; blood pressure, in heart tissues; fasting glucose, in pancreatic islets; cholesterol, in liver tissue; and Alzheimer’s disease, in CD14 monocytes.

Kellis says these findings are significant because they suggest new avenues for treatment that may not have been explored otherwise. In making the new map of the human epigenome available to others in academia, he says that he and his collaborators hope that they can pave the way for future research in this area and “spearhead the use of epigenomics in medicine and therapeutics.”

“The main direction for us is…to use the information that we’ve [presented] so we can get a deeper understanding of the molecular basis of human disease,” Kellis says. “That’s going to take many years and the efforts of many labs but it’s something that’s uniquely enabled by the map that we have made available.”