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Application of "Omics" and Systems Biology to Sarcoidosis Research.

ABSTRACT: Sarcoidosis is a complex, polygenic disease of unknown cause with diverse clinical phenotypes, ranging from self-limited, asymptomatic disease to life-altering symptoms and early disease-related mortality. It is unlikely that a single common environmental exposure (e.g., infection, antigen) entirely explains the disease, and numerous genetic mutations are associated with the disease. As such, it is reasonable to assume, as with other phenotypically diverse diseases, that distinct genetic mechanisms and related biological biomarkers will serve to further define sarcoidosis subphenotypes, mechanisms, and possibly etiology, thus guiding personalized care. The fields of "omics" and systems biology research are widely applied to understand polygenic and phenotypically diverse diseases, such as sarcoidosis. "Omics" refers to technologies that allow comprehensive profiling of sets of molecules in an organism. Systems biology applies advanced computational approaches to make sense of the enormous data sets that are typically generated from "omics" platforms. The primary objectives of this article are to review the available "omics" tools, assess the current status of "omics" and systems biology research in the field of sarcoidosis, and consider how this technology could be applied to advance our understanding of the mechanistic underpinnings of disease and to develop novel treatments.

SUBMITTER: Crouser ED

PROVIDER: S-EPMC5822413 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Application of "Omics" and Systems Biology to Sarcoidosis Research.

Crouser Elliott D ED Fingerlin Tasha E TE Yang Ivana V IV Maier Lisa A LA Nana-Sinkam Patrick P Collman Ronald G RG Kaminski Naftali N

Annals of the American Thoracic Society 20171201 Supplement_6

Sarcoidosis is a complex, polygenic disease of unknown cause with diverse clinical phenotypes, ranging from self-limited, asymptomatic disease to life-altering symptoms and early disease-related mortality. It is unlikely that a single common environmental exposure (e.g., infection, antigen) entirely explains the disease, and numerous genetic mutations are associated with the disease. As such, it is reasonable to assume, as with other phenotypically diverse diseases, that distinct genetic mechani ...[more]

PMID: 29053026

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Project description:The enormous diversity of proteoforms produces tremendous complexity within cellular proteomes, facilitates intricate networks of molecular interactions, and constitutes a formidable analytical challenge for biomedical researchers. Currently, quantitative whole-proteome profiling often relies on non-targeted liquid chromatography-mass spectrometry (LC-MS), which samples proteoforms broadly, but can suffer from lower accuracy, sensitivity, and reproducibility compared with targeted LC-MS. Recent advances in bottom-up proteomics using targeted LC-MS have enabled previously unachievable identification and quantification of target proteins and posttranslational modifications within complex samples. Consequently, targeted LC-MS is rapidly advancing biomedical research, especially systems biology research in diverse areas that include proteogenomics, interactomics, kinomics, and biological pathway modeling. With the recent development of targeted LC-MS assays for nearly the entire human proteome, targeted LC-MS is positioned to enable quantitative proteomic profiling of unprecedented quality and accessibility to support fundamental and clinical research. Here we review recent applications of bottom-up proteomics using targeted LC-MS for systems biology research. SIGNIFICANCE: Advances in targeted proteomics are rapidly advancing systems biology research. Recent applications include systems-level investigations focused on posttranslational modifications (such as phosphoproteomics), protein conformation, protein-protein interaction, kinomics, proteogenomics, and metabolic and signaling pathways. Notably, absolute quantification of metabolic and signaling pathway proteins has enabled accurate pathway modeling and engineering. Integration of targeted proteomics with other technologies, such as RNA-seq, has facilitated diverse research such as the identification of hundreds of "missing" human proteins (genes and transcripts that appear to encode proteins but direct experimental evidence was lacking).

Dataset Information

Application of "Omics" and Systems Biology to Sarcoidosis Research.

Publications

Application of "Omics" and Systems Biology to Sarcoidosis Research.

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