The proteome and its dynamics: A missing piece for integrative multi-omics in schizophrenia.

ABSTRACT

The complex and heterogeneous pathophysiology of schizophrenia can be deconstructed by integration of large-scale datasets encompassing genes through behavioral phenotypes. Genome-wide datasets are now available for genetic, epigenetic and transcriptomic variations in schizophrenia, which are then analyzed by newly devised systems biology algorithms. A missing piece, however, is the inclusion of information on the proteome and its dynamics in schizophrenia. Proteomics has lagged behind omics of the genome, transcriptome and epigenome since analytic platforms were relatively less robust for proteins. There has been remarkable progress, however, in the instrumentation of liquid chromatography (LC) and mass spectrometry (MS) (LCMS), experimental paradigms and bioinformatics of the proteome. Here, we present a summary of methodological innovations of recent years in MS based proteomics and the power of new generation proteomics, review proteomics studies that have been conducted in schizophrenia to date, and propose how such data can be analyzed and integrated with other omics results. The function of a protein is determined by multiple molecular properties, i.e., subcellular localization, posttranslational modification (PTMs) and protein-protein interactions (PPIs). Incorporation of these properties poses additional challenges in proteomics and their integration with other omics; yet is a critical next step to close the loop of multi-omics integration. In sum, the recent advent of high-throughput proteome characterization technologies and novel mathematical approaches enable us to incorporate functional properties of the proteome to offer a comprehensive multi-omics based understanding of schizophrenia pathophysiology.