Realizing the full potential of RNA-Seq will eventually involve incorporating multiple levels of discrete data types and model systems (Fig. 11.12). The entire complement of RNA molecules, including miRNAs and lncRNAs, exists as a highly orchestrated network, regulated in part by genetic variants or epigenetic phenomena spread throughout the genome. Alternative splicing of mature RNA enables considerable bio-diversity of protein products and protein–protein interaction networks. The human proteome (Rual et al., 2005) is far from complete and will likely evolve in parallel with information gleaned from the transcriptome. In the long term, such information will further inform the interpretation of neurophysiological and neuroanatomical studies, including large-scale initiatives like the Human Connectome Project (Van Essen et al., 2013, 2012), in human health. A major challenge will be distilling the vast amount of biological data that bridge multiple scales and also are linked to discrete phenotypes. Focusing on intermediate phenotypes of complex traits may be useful for discovering large, consistent effects exerted by gene networks.
