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Alanis-Lobato, G.

Publications and source records attributed to Alanis-Lobato, G..

2 recordsLinked to original sources

The latent geometry of the human protein interaction network

To mine valuable information from the complex architecture of the human protein interaction network (hPIN), we require models able to describe its growth and dynamics accurately. Here, we present evidence that uncovering the latent geometry of the hPIN can ease challenging problems in systems biology. We embedded the hPIN to hyperbolic space, whose geometric properties reflect the characteristic scale invariance and strong clustering of the network. Interestingly, the inferred hyperbolic coordinates of nodes capture biologically relevant features, like protein age, function and cellular localisation. We also realised that the shorter the distance between two proteins in the embedding space, the higher their connection probability, which resulted in the prediction of plausible protein interactions. Finally, we observed that proteins can efficiently communicate with each other via a greedy routeing process, guided by the latent geometry of the hPIN. When analysed from the appropriate biological context, these efficient communication channels can be used to determine the core members of signal transduction pathways and to study how system perturbations impact their efficiency.

systems biology

A reliable and unbiased human protein network with the disparity filter

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 networks weight and connectivity properties.

bioinformatics