Brown researchers use wildcards to develop better way to sequence DNA

Two Brown computer science professors are working on a method to sequence DNA that they believe will be faster and more efficient than the technique currently used by mappers of the human genome. Franco Preparata and Eliezer Upfal are attempting to make improvements to a lesser-used method known as sequencing by hybridization. In their method, they insert gaps that act as wildcards in DNA probes.

When sequencing DNA, scientists look for the arrangement of bases (amino acids represented by the letters C,T,G and A) contained in a particular strand of DNA, which is too small to be seen under a microscope.

In the decade-old hybridization method, short sequences of DNA bases six to 20 bases long are used as probes to find the bases contained in a long string of DNA. The DNA to be sequenced binds to some of the probes on a tiny glass chip called a microarray.

The target DNA binds to probes that match its sequence (T always pairs with A, and G always pairs with C). Then the DNA can be detected and read. Using the information obtained from the probes on the microarray, a computer program is then used to construct the long sequence of bases in the target DNA strand. Current techniques can construct only a few hundred bases.

What we show is that you would be able to sequence a substantially longer piece of DNA, Upfal said. Instead of a few hundred bases, you could do tens of thousands.

Based on a novel mathematical insight, Preparata and Upfal have designed a new pattern for the probes on the chip. In the new pattern, some of the DNA bases in each probe are replaced by gaps that act like wildcards. The new design extracts substantially more information about the DNA

Contact: Janet Kerlin
Brown University

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