The living cell operates thanks to an intricate network of protein interactions. Proteins activate, transport, degrade, stabilise and participate in the production of other proteins. As a result, a reliable and systematically generated protein wiring diagram is crucial for a deeper understanding of cellular functions. Unfortunately, current human protein networks are noisy and incomplete. Also, they suffer from both study and technical biases: heavily studied proteins (e.g. those of pharmaceutical interest) are known to be involved in more interactions than proteins described in only a few publications. Here, we use the experimental evidence supporting the interaction between proteins, in conjunction with the so-called disparity filter, to construct a reliable and unbiased proteome-scale human interactome. The application of a global filter, i.e. only considering interactions with multiple pieces of evidence, would result in an excessively pruned network. In contrast, the disparity filter preserves interactions supported by a statistically significant number of studies and does not overlook small-scale protein associations. The resulting disparity-filtered protein network covers 67% of the human proteome and retains most of the network's weight and connectivity properties.
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