Researchers at the University of Massachusetts Medical School (UMMS) have designed a new method to assemble the brief snippets of DNA generated by human genome sequencing technologies. By looking to the fragments’ three-dimensional structure and the frequency of their interactions, Job Dekker, PhD, and his colleagues have been able to situate 65 previously unaccounted for pieces within the complete genome. Details of the study were published online in Nature Biotechnology.
Over the past 10 years, the cost of high-throughput DNA sequencing has dropped to a few thousand dollars and enabled the simultaneous reading of hundreds of millions of DNA fragments. Computer algorithms are responsible for matching these fragments into larger overlapping pieces. However, the human genome consists of thousands of highly repetitive cycles of DNA. For each fragment, dozens of possible locations exist. In a process called genome scaffolding, researchers have been using painstaking, labor-intensive experimental methods to assign the 100,000 remaining fragments to their rightful place.
“How to assemble these snippets of DNA has become a bottleneck for researchers that can take weeks or months to solve,” said Noam Kaplan, PhD, first author of the Nature Biotechnology study.
To streamline the process, Dekker and Kaplan used Hi-C technology developed by the Dekker laboratory to measure how often each DNA fragment interacted with others. Because of the genome’s three-dimensional structure, fragments located closer together interact more often than those farther apart. Computers helped assign a location to 65 snippets based on both their linear sequencing and physical structure.
“We were surprised how well our method worked,” Kaplan said. “It is satisfying to see how a simple idea can solve such a difficult and common problem.”
Dekker also noted, “This new approach to genome assembly can help produce higher-quality genome sequences faster and easier than current methods. It will be especially interesting to apply this method to identify chromosomal aberrations, which are a hallmark of cancer.”
For more information, visit Nature Biotechnology.