Abstract
The Salk Institute has announced a new algorithm that can help pinpoint key disease-causing regions within a genome with more accuracy. The new system, called “regulatory-element prediction based on tissue-specific local epigenomic signatures”—or REPTILE, for short—combines histone modification and methylation data to predict regions of the genome that contain sections of DNA called enhancers, which have proven to be important to disease research.
Only 2% of DNA is made up of genes; the rest was considered to be “junk,” according to Salk researchers. REPTILE is helping to prove that this so-called junk is not really junk at all, but instead plays a valuable role in disease research. Sections of this “junk DNA” contain enhancers that show where and when the gene information is read out. Mutations in enhancers are now tied to disease, but finding these enhancers has been difficult in the past.
“These regions don’t code for proteins, but they still contain genetic variants that cause disease,” said Joseph Ecker, Ph.D., senior author of the study, Howard Hughes Medical Institute investigator and director of Salk’s Genomic Analysis Laboratory. “We just haven’t had very effective tools to locate these areas in a variety of tissues and cell types—until now.”
According to Salk, REPTILE allows for “vastly more targeted searches for disease-causing genetic variants in the human genome,” including those that promote cancer or cause metabolic disorders.
“The novelty of this method is that it uses DNA methylation to really narrow down the candidate regulatory sequences suggested by histone modification data,” said lead study investigator Yupeng He, a graduate student at the Salk Institute. “We were then able to test REPTILE’s predictions in the lab and validate them with experimental data, which gave us a high degree of confidence in the algorithm’s ability to find enhancers.”
“The nice thing about this tool is you can train it on one type of data and use it on another type of data,” Eckers said. Training the tool on stem cells first will allow REPTILE to search for enhancers on more difficult cells.