Denoising large-scale biological data using network filters

Abstract

Background: Large-scale biological data sets are often contaminated by noise, which can impede accurate inferences about underlying processes. Such measurement noise can arise from endogenous biological factors like cell cycle and life history variation, and from exogenous technical factors like sample preparation and instrument variation. Results: We describe a general method for automatically reducing noise in large-scale biological data sets. This method uses an interaction network to identify groups of correlated or anti-correlated measurements that can be combined or “filtered” to better recover an underlying biological signal. Similar to the process of denoising an image, a single network filter may be applied to an entire system, or the system may be first decomposed into distinct modules and a different filter applied to each. Applied to synthetic data with known network structure and signal, network filters accurately reduce noise across a wide range of noise levels and structures. Applied to a machine learning task of predicting changes in human protein expression in healthy and cancerous tissues, network filtering prior to training increases accuracy up to 43% compared to using unfiltered data. Conclusions: Network filters are a general way to denoise biological data and can account for both correlation and anti-correlation between different measurements. Furthermore, we find that partitioning a network prior to filtering can significantly reduce errors in networks with heterogenous data and correlation patterns, and this approach outperforms existing diffusion based methods. Our results on proteomics data indicate the broad potential utility of network filters to applications in systems biology.