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University Of Massachusetts Medical School scientists re-imagine how genomes are assembled
Date:11/25/2013

rt pieces and need to be assembled into larger pieces using computer algorithms that can match up overlapping pieces. The end result of this initial assembly is typically a set of as many as 100,000 DNA fragments which then need to be organized with respect to one another in the correct order to create a complete genome.

Hindering this final task is the fact that genomes are full of highly repetitive sequences that appear in a multitude of places. Finding where precisely, among the thousands of possible locations, a particular fragment of DNA resides, is a daunting task. To complete this second step, often referred to as genome scaffolding, scientists rely on labor intensive, low-through put experimental techniques to build reasonably accurate, complete genomes.

"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, postdoctoral research fellow in the Dekker lab and first author of the Nature Biotechnology study.

Tackling this problem, Dekker and Kaplan looked to the three-dimensional structure of the genome as a guide for assembling the linear DNA sequences. Using Hi-C technology, developed by the Dekker lab, they measured how frequently each DNA fragment in the genome interacts with others. DNA sequences that are located near each other in the three dimensional genome tend to interact more frequently, while DNA sequences that are further apart interact less frequently. Computational methods are then used to mathematically determine the linear genomic position of each fragment in the genome based on the 3D interaction frequency data that fits that sequence.

For example, said Kaplan, a sequence may fit into the one-dimensional linear genome in several places. But using the interaction frequency data, it is possible to determine the relationship it has with other sequences and whether it is close to or far away from those sequences. "So whi
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Contact: Jim Fessenden
james.fessenden@umassmed.edu
508-856-2000
University of Massachusetts Medical School
Source:Eurekalert  

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