ICoN: integration using co-attention across biological networks

Abstract

Motivation

Molecular interaction networks are powerful tools for studying cellular functions. Integrating diverse types of networks enhances performance in downstream tasks such as gene module detection and protein function prediction. The challenge lies in extracting meaningful protein feature representations due to varying levels of sparsity and noise across these heterogeneous networks.

Results

We propose ICoN, a novel unsupervised graph neural network model that takes multiple protein–protein association networks as inputs and generates a feature representation for each protein that integrates the topological information from all the networks. A key contribution of ICoN is exploiting a mechanism called “co-attention” that enables cross-network communication during training. The model also incorporates a denoising training technique, introducing perturbations to each input network and training the model to reconstruct the original network from its corrupted version. Our experimental results demonstrate that ICoN surpasses individual networks across three downstream tasks: gene module detection, gene coannotation prediction, and protein function prediction. Compared to existing unsupervised network integration models, ICoN exhibits superior performance across the majority of downstream tasks and shows enhanced robustness against noise. This work introduces a promising approach for effectively integrating diverse protein–protein association networks, aiming to achieve a biologically meaningful representation of proteins.

Availability and implementation

The ICoN software is available under the GNU Public License v3 at https://github.com/Murali-group/ICoN.