Musings Beyond the Human Genome: What Will Become of the Titans of Sequencing?

Editor's note: An earlier version of this article contained information erroneously given by Graham Scott, an assistant professor at Baylor College of Medicine's HumanGenomeSequencingCenter. Scott had said Baylor is working with California's Parallele to use Affymetrix chip technology in the government-funded human haplotype-mapping project. In fact, though Baylor is interested in participating in the HapMap project, it is not currently involved with it. The college is working with Parallele for large-scale genotyping projects.

BOSTON, Oct. 3 - Now that the human-genome project is wrapping up, the future of the massive government-funding sequencing centers--the Whiteheads and Baylors of the world--seems to be falling under a shadow.

Without that billion-dollar juggernaut, what will be their reason for living? How will they be able to justify the shiny new sequencing machines, the top-flight bioinformaticists, all those expensive reagents? Who will save them from turning into sequencers-for-hire--into genomic hacks?

Chickens, chimpanzees, and world-class medical specialists, say representatives from two of the country's major public genome-sequencing centers.

At a roundtable organized by Genome Technology magazine at TIGR's GSAC meeting here today, WashingtonUniversity's Elaine Mardis and Baylor College of Medicine's Graham Scott argued that the powerful sequencing centers that led the public human-genome effort will be equally important in this next phase of genomic science.

"I rail against the idea of a 'post-genomic era,'" said Mardis, who is the director of technology development at the GenomeSequencingCenterat WashingtonUniversityMedicalSchool, which churns through 30 million lanes of DNA a year. "There's so much other cool stuff out there to learn about."

The projects that will demand her talents: new sequencing efforts like the honeybee, the chimp, and the cow; expanding beyond pure-play DNA sequencing; and launching new clinical programs that make use of these institutions' close ties with top-flight doctors.

Mardis said that Wash U's machines will be kept busy with DNA from the chimp and the chicken, the lab's newest project. "It's a major branch in the evolutionary tree--and it's darn tasty, too," she quipped.

On the Baylor side, more than 80 percent of the school's capacity is devoted to human and rat work. That will soon shift--the genome center is already booked up for the next three years with efforts to sequence the honeybee, the sea urchin, and a solo project to conquer Drosophila obscura, the famous fruitfly's lesser-known cousin.

Besides just taking on new critters, these centers will also tackle new types of projects, broadening their efforts and expanding into different kinds of genetic science. Baylor is working with California's Parallele to use Affymetrix chip technology for large-scale genotyping. "It's our first highly funded exploration into microarrays," said Scott, an assistant professor with the medical school's HumanGenomeSequencingCenter. "It's a cool technology."

At WashingtonU, said Mardis, one new effort will pair a project to sequence a pathogenic fungus with microarray-based annotation. The center will probably also get more involved in genome analysis.

And since both genome centers are based at major medical schools, each will probably find itself much more involved in clinical research. Washington's genome center is already setting up an independent resequencing pipeline for projects to investigate the genetic underpinnings of disease.

"We're both incredibly fortunate to be at medical schools replete with top-notch clinicians, people who are focused on understanding disease and accumulating samples," said Mardis.   "It's a confluence: We have the reference sequence, the clinicians have lots of patients samples and want to set up intelligent ways to understand these diseases."

"Genome centers are a Meccafor increasing numbers of doctors who might have an interest in a specific disease," agreed Scott. "Baylor is incredibly well-positioned, with lots of relationships with clinicians."

These kinds of research--getting more closely involved in medical work, understanding new organisms, moving from pure sequencing to annotation and expression--will permit the kind of broad-minded human biology that the genome project was always intended to generate, the two sequencers agreed. And, they said, it should also finally bring in the era we've all been waiting for: when data on DNA turns into practical knowledge.

"It's the epitome of why we sequenced the human genome," said Mardis.