The genome has been the core focus of biomedical research for twenty years. Although the genome is prewritten and predetermined, much biology happens after it appears. One area is epigenomics, which is the modification of genomic outcomes. Bret Barnes has spent his career at Illumina developing the DNA methylation Infinium arrays that have become the workhorse of epigenomic studies around the world. Barnes says he was torn as a young person between biochemistry and computer science. He fortuitously ended up at UC Santa Cruz when they launched the first bioinformatics degree. Early on, he was interested in protein structure prediction. “There are 20 amino acids,” he said. “Way more exciting than DNA with only four bases.” But then he discovered the fifth base. “Methylated cystine is the fifth base. So five, not four — a little better,” he continues. At the time of the Solexa acquisition, Illumina recruited Bret to do bioinformatics work on DNA methylation. “If the king and queen of DNA methylation at Illumina were Kevin Gunderson and Marina Bibikova, then you could think of me as the prince or maybe the joker,” he says, tongue in cheek. Where are we at today in epigenomics? What applications does Barnes see for the actionable epigenome, and how is the field developing? This is a public episode. If you’d like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe