Minireview: progress and challenges in proteomics data management, sharing, and integration

Abstract

The proteome represents the identity, expression levels, interacting partners, and posttranslational modifications of proteins expressed within any given cell. Proteomic studies aim to census the quantitative and qualitative factors regulating the biological relationships of proteins acting in concert as functional cellular networks. In the field of endocrinology, proteomics has been of considerable value in determining the function and mechanism of action of endocrine signaling molecules in the cell membrane, cytoplasm, and nucleus and for the discovery of proteins as candidates for clinical biomarkers. The volume of data that can be generated by proteomics methodologies, up to gigabytes of data within a few hours, brings with it its own logistical hurdles and presents significant challenges to realizing the full potential of these datasets. In this minireview, we describe selected current proteomics methodologies and their application in basic and translational endocrinology before focusing on mass spectrometry as a model for current progress and challenges in data analysis, management, sharing, and integration.

Fig. 1.

Proteomics elucidates function and mechanism in molecular endocrinology. The schematic shows events on which proteomics reports in general functional models of G protein-coupled receptor and NR signaling. The binding of a variety of peptide ligands to G protein-coupled receptors (GPCR) induces recruitment of intracellular interacting partner proteins, touching off a variety of kinase cascades with functional endpoints in the cytoplasm (phosphorylated target protein) and nucleus. Nuclear targets of kinase cascades include transcription factors (TF), NR, and coregulators (CoR), which collectively modulate target gene expression and de novo protein synthesis. NR ligands bind directly to NR (the classic genomic model), inducing the recruitment of coregulators and modulating expression of target genes. Certain NR ligands have also been reported to elicit rapid cellular effects via cross talk with cellular kinase cascades (the nongenomic model). Phosphorylation events upon which phosphoproteomics reports are indicated.

Fig. 2.

Available standards for the lifecycle of MS experimentation. From initial experimental design to the publication of MS results (steps, left), standard protocols, analysis pipelines, data structures, and guidelines/recommendations for publishers (considerations, right) have been developed, although the relative maturity of each may differ. LIMS, Laboratory information management systems; m/Q, mass-to-charge ratio.