Genome-wide data sets are increasingly being used to identify biological pathways and networks underlying complex diseases. In particular, analyzing genomic data through sets defined by functional pathways offers the potential of greater power for discovery and natural connections to biological mechanisms. With the burgeoning availability of next-generation sequencing, this is an opportune moment to revisit strategies for pathway-based analysis of genomic data. Here, we synthesize relevant concepts and extant methodologies to guide investigators in study design and execution. We also highlight ongoing challenges and proposed solutions. As relevant analytical strategies mature, pathways and networks will be ideally placed to integrate data from diverse -omics sources to harness the extensive, rich information related to disease and treatment mechanisms.
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