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The big ome

It's time to make the case for proteins.

'The body's building blocks', 'cellular machinery': proteins are sometimes stuck with rather mundane labels. Certainly they sit in the scientific shadow of the genome sequence and the eulogies that inspires. So protein biologists face an uphill battle if they are to fire up the research community — and the world beyond — enough to buy into a Human Proteome Project.

The project is just getting past the back-of-the-envelope stage but, in essence, it would systematically catalogue all the proteins manufactured in the body: what they are, where they are and in what abundance (see page 920). A cancer biologist might reveal whether a rogue protein is overexpressed in the tumours she studies compared with levels from healthy tissue that are logged in the proteome register. A geneticist who traces Alzheimer's susceptibility to a region of code could consult the proteome to reveal which proteins are being manufactured from that region in the brain. We can expect this catalogue of proteins to eventually include the targets for almost all future drugs.

There are many obvious parallels with efforts to elucidate the human genome. A human proteome would be a very expensive and ambitious undertaking and, by its nature, the full benefits cannot be spelt out beforehand. That's how it should be. The fun of the human genome is that spelling out the letters did little to decipher the code — there is so much more complexity than had ever been imagined. We can expect that the proteome will also reveal unexpected delights about the ways in which proteins rally together to perform a task or become tissue.

And yet there was a certain intellectual allure about 'cracking' the human genome that, on the face of it, is lacking from cataloguing all the proteins. And although the human genome is finite, the proteome is almost boundless, because each of the body's proteins may be present in different forms and different amounts in each tissue — and even in precisely the same cell from one moment to the next. That very complexity, however, should inspire, not dissuade.

Proteomic analyses have also been viewed with some scepticism, in part because many studies involving mass-spectrometry profiling have proved difficult to reproduce. And the field has so far largely failed to deliver the disease-tracking biomarkers on which these early efforts were sold. There are few examples of clear, clinically proven benefits. Starting out with this kind of reputation will make a Human Proteome Project particularly hard to sell.

The Human Proteome Organisation (HUPO) has taken some praiseworthy steps towards resolving these issues with, for example, a project to show that different labs can now produce identical results from the same sample. With the rapid evolution of proteomic techniques, the field's reputation and utility is likely to pick up. But HUPO — and the proteomics community — still has a lot to prove and a successful Human Proteome Project is its chance to prove it. It needs to consult widely to devise a strategy that has strong community backing. It will also need to demonstrate that the knowledge stemming from this project will transform the research landscape in the same way that the genome sequence has done.

Failing these, either the project will die or HUPO could risk being left on the sidelines as organizations with money to spend make the decisions about how proteomics should be done.

Times have changed since the Human Genome Project — proposals for mega-biology projects are rather more common and money scarcer. HUPO, and all biologists who love proteins, should articulate clearly and loudly the benefits of sinking US$1 billion into protein biology. It will take much work to get due recognition for the 'cell's work-horses'.

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The big ome. Nature 452, 913–914 (2008). https://doi.org/10.1038/452913b

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