Integrative systems biology and networks in autophagy.

The growing recognition that autophagy has important roles in many biological pathways, physiological systems, and infection and disease states necessitates a multidimensional perspective and systems-wide understanding of how autophagy is triggered or modulated by diverse stimuli. To delineate the nonlinearity and combinatorial complexity of biological networks and signaling pathways impinging on autophagy requires an integrative framework that brings together diverse information from genome-scale data (genomics, transcriptomics, proteomics, interactomics, functional RNAi screens) to dynamic time-series analyses and biochemical assays across a variety of biological and clinical contexts. We outline recent applications of genome-wide approaches to studying autophagy and highlight how some of these could be integrated to derive sub-networks that are more functionally focused. Viewed from a network perspective, the extensive interconnectivity between pathway systems converging on autophagy provides the essential foundation from which to systematically elucidate the regulatory nuances and crosstalks that orchestrate autophagic processes in different pathophysiological contexts.