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Urging Researchers to Forget the Genome, Sydney Brenner Sells a Cell Map

NEW YORK, Sept. 9 - The next big genomics project may not be a genomics project at all, if Sydney Brenner has anything to do with it.


The 75-year-old driving force behind the Fugu genome project is urging the scientific community to step back a bit from the genome and focus on a new mission: Creating a function-based cell map by 2020.


Consistent with his lifelong reputation as a visionary and provocateur, Brenner challenged a crowd of over 250 bioinformaticists gathered at the Wellcome Trust Genome Campus in Hinxton, UK, to "forget the genome."


"The more you annotate the genome, the more you make it opaque," he warned in a keynote speech delivered at the joint Cold Spring Harbor Laboratory/Wellcome Trust Genome Informatics conference on Saturday. "We need to focus on our cells."


Brenner questioned the ability of computational approaches to derive functional knowledge from genomic sequence alone--a "hideously difficult task," he said--because some problems are simply "not soluble or computable." The future, according to Brenner, requires going back to the bench. Old-fashioned data on the biochemistry of the cell would then be used to flesh out the cell map, which would serve as "a framework to think of genomes and their products."


Brenner proposed reducing the complexity of the task by simplifying the representative structure of the cell. Because function is based on interactions between subcellular products, he noted, studying these products in their aggregate form would be preferable to a product-by-product approach. The first step, he said, is tackling what he termed the "instantiation problem--a phrase carefully selected based on its inability to tag with the "omics" suffix, he quipped.


One instantiation might be the expression of a product in a given cell type, he offered as an example, while another might be variable splicing in either the same cell type or different cell types. The goal of the cell map project, therefore, would be to measure and represent all the instantiations in a variety of cell types in a series of databases.


The 2020 completion date was chosen based on the time it took the Human Genome Project to bear fruit from the time of its conception, Brenner said, adding that the association with "good vision" played a bit of a role as well.


Noting that the cell map databases would be "accurate and complete," Brenner criticized current bioinformatics resources for being "too full of noise." While not questioning the value of bioinformatics, Brenner said he disagrees with "people who think they can find everything that way."


As an early proponent of computational approaches to biological research, Brenner said this view came from his own experiences: In the mid-60s, his lab tried to use computers to reconstruct biological systems. "We thought we had so much data," he said, echoing a familiar refrain heard in bioinformatics circles today, "but we were 30 years too early."