Network Enhancement: a general method to denoise weighted biological networks

Abstract

Networks are ubiquitous in biology where they encode connectivity patterns at all scales of organization, from molecular to the biome. However, biological networks are noisy due to the limitations of technology used to generate them as well as inherent variation within samples. The presence of high levels of noise can hamper discovery of patterns and dynamics encapsulated by these networks. Here we propose Network Enhancement (NE), a novel method for improving the signal-to-noise ratio of undirected, weighted networks, and thereby improving the performance of downstream analysis. NE applies a novel operator that induces sparsity and leverages higher-order network structures to remove weak edges and enhance real connections. This iterative approach has a closed-form solution at convergence with desirable performance properties. We demonstrate the effectiveness of NE in denoising biological networks for several challenging yet important problems. Our experiments show that NE improves gene function prediction by denoising interaction networks from 22 human tissues. Further, we use NE to interpret noisy Hi-C contact maps from the human genome and demonstrate its utility across varying degrees of data quality. Finally, when applied to fine-grained species identification, NE outperforms alternative approaches by a significant margin. Taken together, our results indicate that NE is widely applicable for denoising weighted biological networks, especially when they contain high levels of noise.