RESEARCH HIGHLIGHTS SYSTEMS BIOLOGY An expanded human interactome An expanded catalog of binary biophysical of the interactions with orthogonal assays, more studied also in terms of their interac- interactions between human proteins. Roth, Vidal and colleagues report a map tions. (It should be noted, that the Y2H data Most biological processes involve molecu- of almost 14,000 high-quality interactions set also has biases; for instance, it is depleted lar interactions. Although there have been between 4,303 proteins. of membrane proteins.) The quality of the many studies of one such interaction type, When they compared the resulting data set Y2H interactions in sparse zones is no lower protein-protein interactions, the current to the set of about 11,000 high-quality binary than that in dense zones. list of binary human protein interactions is interactions in the literature as of 2013 (‘high What of the biological relevance of the thought to be far from the ‘complete’ inter- quality’ is here defined as being supported by interactions? The Y2H assay reports possible actome. multiple lines of evidence), the authors saw a physical interactions between the assayed Frederick Roth at the University of Toronto marked difference in the distribution across proteins within the heterologous confines and Marc Vidal at the Dana-Farber Cancer the ‘publication-ranked interactome space’. of the yeast nucleus. The expanded data set, Institute, and colleagues, now describe an Proteins on which many papers have been Roth and colleagues show, is enriched for expanded data set of binary biophysical inter- published have many literature-reported protein pairs with features indicating that actions between human proteins. Building interactions, whereas proteins on which few their interactions are likely to be meaning- on extensive experience using the yeast two- papers have been published have an appar- ful. But further analysis is always necessary hybrid (Y2H) method to make high-quality ently sparse interactome. The new Y2H to determine whether a particular interaction interactome maps, the team probed all binary data set, by contrast, is more homogeneous, occurs biologically and if it is important for interactions between proteins encoded by reporting interactions across this spectrum. the cell types or process under study. about 13,000 genes. Benchmarking assay This suggests that the ‘sparse zones’ in Natalie de Souza performance with literature-curated refer- literature-curated interaction data at least RESEARCH PAPERS ence sets, they observed no loss of precision partly reflect sociological biases rather than Rolland, T. et al. A proteome-scale map of the human or sensitivity at this scale. After validation biological laws: heavily studied proteins are interactome network. Cell 159, 1212–1226 (2014). Nature America, Inc. All rights reserved. America, Inc. Nature 5 © 201 npg NATURE METHODS | VOL.12 NO.2 | FEBRUARY 2015 | 107.