25057 Gen Seq

Thursday, April 15, 2010

New Tricks for Genome Sequencing

Sequencing is being used to track how the immune system changes over time, to measure gene expression and to analyse protein translation.

By Emily Singer

Now that fast and cheap sequencing is readily available, scientists are applying it in a number of creative ways. Details of some of those efforts emerged at a conference onNetwork Biology this week at the Broad Institute, in Cambridge, MA.

George Church, director of the Personal Genome Project (PGP) and a pioneer in genomics technologies at Harvard, is using sequencing to track the "immune-one"--how individual's immune systems change over time. In a collaboration with Roche, his team is analyzing antibodies in people before and after vaccinations for flu and hepatitis B. "We have two years of data on vaccines from PGP volunteers," he said at the conference. "We're seeing interesting results reflective of the vaccines we used."

Stephen Turner, founder and chief technology officer for Pacific Biosciences, discussed his company's sequencing machine, slated to begin shipping to the first recipients in the next few weeks. In collaboration with the New York Department of Health, scientists used the technology to analyze influenza strains in individual patients during the H1N1 outbreak. "We could go from extraction from the patient to a printed report in the hands of an epidemiologist in about nine hours," says Turner. Quick analysis methods would help public health surveillance efforts.

Turner also described two new applications for Pacific Biosciences sequencing machines: detecting methylation patterns and tracking protein translation. Methylation is a key measure in the fast-growing field of epigenetics, broadly defined as molecular changes that affect gene expression but not the DNA sequence itself. It is these changes that enable genetically identical cells to develop into both brain cells and blood cells and have been linked to learning, addiction, cancer and obesity among myriad other states. Methylation is one mechanism for changing gene expression, turning on and off certain genes. The Pacific Biosciences technology reads DNA sequence by detecting the addition of single bases onto individual DNA molecules. Scientists discovered that the time it takes for this base to be added depends on whether the molecule is methylated at that position, enabling detection of methylation patterns in real time.

In a second novel application, developed in collaboration with Joe Puglisi at Stanford University, scientists adapted the sequencing technology to observe the ribosome--the molecular machinery that translates RNA into proteins. The research was published today in the journal Nature. Initially, the technique will be used to study the process of translation. But Turner said it might one day be used to examine off-target effects of drugs, for example, by examining how a specific drug altered translation of non-target proteins.

Both Church and Turner touched on the next brass ring for genomics technologies; a handheld sequencing device. Church predicted a demonstration device within the next two years, settling on Ion Torrent as the most likely frontrunner. Turner predicted that the next generation of Pacific Biosciences sequencing machine could provide the basis for a handheld sequencer.