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January 5, 2010
Run It Past the Chemists
I missed this paper when it came out back in October: "Reactome Array: Forging a Link Between Metabolome and Genome". I'd like to imagine that it was the ome-heavy title itself that drove me away, but I have to admit that I would have looked it over had I noticed it.
And I probably should have, because the paper has been under steady fire since it came out. It describes a method to metabolically profile a variety of cells though the use of a novel nanoparticle assay. The authors claim to have immobilized 1675 different biomolecules (representing common metabolites and intermediates) in such a way that enzymes recognizing any of them will set off a fluorescent dye signal. It's an ingenious and tricky method - in fact, so tricky that doubts set in quickly about the feasibility of doing it on 1675 widely varying molecular species.
And the chemistry shown in the paper's main scheme looks wonky, too, which is what I wish I'd noticed. Take a look - does it make sense to describe a positively charged nitrogen as a "weakly amine region", whatever that is? Have you ever seen a quaternary aminal quite like that one before? Does that cleavage look as if it would work? What happens to the indane component, anyway? Says the Science magazine blog:
In private chats and online postings, chemists began expressing skepticism about the reactome array as soon as the article describing it was published, noting several significant errors in the initial figure depicting its creation. Some also questioned how a relatively unknown group could have synthesized so many complex compounds. The dismay grew when supplementary online material providing further information on the synthesized compounds wasn’t available as soon as promised. “We failed to put it in on time. The data is quite voluminous,” says co-corresponding author Peter Golyshin of Bangor University in Wales, a microbiologist whose team provided bacterial samples analyzed by Ferrer’s lab.
Science is also coming under fire. “It was stunning no reviewer caught [the errors],” says Kiessling. Ferrer says the paper’s peer reviewers did not raise major questions about the chemical synthesis methods described; the journal’s executive editor, Monica Bradford, acknowledged that none of the paper’s primary reviewers was a synthetic organic chemist. “We do not have evidence of fraud or fabrication. We do have concerns about the inconsistencies and have asked the authors' institutions to try to sort all of this out by examining the original data and lab notes,” she says.
The magazine published an "expression of concern" before the Christmas break, saying that in response to questions the authors had provided synthetic details that "differ substantially" from the ones in the original manuscript. An investigation is underway, and I'll be very interested to see what comes of it.
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