As part of this work, which was published in Nature in 2003,[32] he developed computational methods to pinpoint patterns of similarity and difference between closely related genomes.

He turned from yeast to flies and ultimately to mammals, comparing multiple species to explore genes, their control elements, and their deregulation in human disease.

He said during an interview with MIT Technology Review[33] “If the genome is the book of life, the epigenome is the complete set of annotations and bookmarks.”[33] His lab now uses this map to further the understanding of fundamental processes and disease in humans.

Kellis and colleagues used epigenomic data to investigate the mechanistic basis of the strongest genetic association with obesity, published in the New England Journal of Medicine.

[17] Kellis, Li-Huei Tsai, and others at MIT used epigenomic markings in human and mouse brains to study the mechanisms leading to Alzheimer’s disease, published in Nature in 2015.

[20] They showed that immune cell activation and inflammation, which have long been associated with the condition, are not simply the result of neurodegeneration, as some researchers have argued.