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Sequencing: Genomics Debate Rages On: Quality or Quantity?

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Across the genomics community, a popular debate pits draft-sequencing lots of organisms against getting higher-quality finished sequences of fewer organisms.

The DOE’s Joint Genome Institute, for example, is known for its marathon microbial sequencing program, which seeks to obtain as many high-throughput draft sequences as resources allow.

“The upside to that is you obtain a lot of information about many organisms,” says Roger Reeves, a mouse genomics researcher at Johns Hopkins University. “The downside is that there are no resources available to ever finish the sequence, and there clearly are things that a complete sequence allows you to do. And one important one is to make negative sequences of what is not there.”

Comparative genomics researchers tend to fall more squarely on the quality-finishing side, though as proponents Eric Green of the NIH and TIGR president Claire Fraser contend, the issue is not so clear-cut that you would find someone arguing solely one side or the other.

“A big issue as we move away from sequencing humans is whether we should spend $100 million to get a finished sequence” of other organisms, such as chicken, Green says, when the shotgun approach costs $30 million to $40 million less.

“At the end of the day, because it is all so new, we don’t know how high-quality a sequence needs to be,” says Green, whose group is working on a cost analysis of the two approaches to try to settle the debate.

Like many scientists, Fraser points out that having a draft sequence is better than having no sequence at all. At TIGR, though, she says total costs for genome finishing are down from 75 percent of total costs to 50 percent.

Some see that as a chance to draft-sequence two organisms for the price of one finished genome. “[But] I would argue that as soon as someone outside of the draft sequencing group starts working with data that is incorrect or incomplete, and needs to start trying to PCR-amplify a missing gene to figure out whether it is there … the cost savings rapidly disappear,” says Fraser.

While this is certainly not a new debate, it remains an important one. “At stake here is the entire value of the Human Genome Project,” says Reeves.

— Dana Frisch

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