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Interactome May Provide Window Into Species Complexity

NEW YORK (GenomeWeb News) – An international team of scientists has developed a strategy for predicting the total size of protein interaction networks from smaller sub-networks — and, they say, their initial results suggest more complex species have more abundant protein interactions.
In a paper published online this week in the Proceedings of the National Academy of Sciences, researchers from Imperial College London in the UK, the Max Planck Institute for Molecular Genetics in Germany, and the University of Aarhus in Denmark used a statistical approach for estimating the size of protein interactomes in several different eukaryotic species. And, for the four species tested at least, they found that biological complexity positively correlated with interactome size.
This may explain a previously puzzling observation: that the number of genes is similar in organisms as seemingly distinct as C. elegans, humans, and rice. It also lends credence to the notion that physiological complexity — including protein interaction networks — might more adequately explain biological complexity than gene content.
“Understanding the human genome definitely does not go far enough to explain what makes us different from more simple creatures,” lead author Michael Stumpf, chair of theoretical systems biology at the Imperial College London, said in a statement. “Our study indicates that protein interactions could hold one of the keys to unraveling how one organism is differentiated from another.”
For this paper, Stumpf and his colleagues created a set of formulas to extrapolate total interactomes from a subset of protein interactions. From this, they estimated that there are roughly 650,000 interactions in the human interactome. That’s about three times bigger than the C. elegans interactome and ten times bigger than the Drosophila interactome. All three organisms seem to have larger interactomes than the yeast Saccharomyces cerevisiae, which is expected to have in the neighborhood of 35,000 protein interactions.
Even so, the researchers did not have enough data to see whether the same pattern held in plants such as maize and rice, which have larger genomes than humans but are not considered as biologically complex.
“Unfortunately, for maize and rice, which have comparable or even larger number of genes to humans, only tiny [protein interaction network] datasets are available and we cannot obtain useful estimates about their respective interactome sizes,” Stumpf and his colleagues wrote. “[I]f interactome size does reflect organismic complexity, then we would expect these organisms to have smaller interactomes than humans.”
But not everyone is convinced that interactomes fully explain biological complexity. In an accompanying commentary in PNAS, Northwestern University chemical and biological engineer Luis Nunes Amaral suggested that Stumpf and his colleagues “may be placing emphasis on the wrong concern.”
He noted that, though it is “surely reassuring to those needing supporting evidence for the greater complexity of Homo sapiens …[i]t takes no more than common sense to realize that humans are more complex than fruit flies or yeasts.” 
Researchers need to address more fundamental questions surrounding systems biology, Amaral argued, such as the nature and organization of biological complexity and strategies for organizing reams of high-throughput data.
Still, he commended Stumpf’s team for providing “convincing estimates of the interactome size of four organisms, including humans.”
“These numbers provide a sobering view of where we stand in our cataloging of the human interactome,” Amaral wrote. “At present, we have identified <0.3 percent of all estimated interactions among human proteins. We are indeed at the dawn of systems biology.”

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