Immune Netw.  2014 Apr;14(2):73-80. 10.4110/in.2014.14.2.73.

Advances in Systems Biology Approaches for Autoimmune Diseases

Affiliations
  • 1Division of Rheumatology, Department of Internal Medicine, Konkuk University Medical Center, Seoul 143-729, Korea. ho0919@kuh.ac.kr
  • 2Division of Rheumatology, Department of Internal Medicine, Konkuk University School of Medicine, Seoul 143-729, Korea.

Abstract

Because autoimmune diseases (AIDs) result from a complex combination of genetic and epigenetic factors, as well as an altered immune response to endogenous or exogenous antigens, systems biology approaches have been widely applied. The use of multi-omics approaches, including blood transcriptomics, genomics, epigenetics, proteomics, and metabolomics, not only allow for the discovery of a number of biomarkers but also will provide new directions for further translational AIDs applications. Systems biology approaches rely on high-throughput techniques with data analysis platforms that leverage the assessment of genes, proteins, metabolites, and network analysis of complex biologic or pathways implicated in specific AID conditions. To facilitate the discovery of validated and qualified biomarkers, better-coordinated multi-omics approaches and standardized translational research, in combination with the skills of biologists, clinicians, engineers, and bioinformaticians, are required.

Keyword

Autoimmune diseases; Systems biology; Multi-omics; Biomarker; Translational research; Network analysis

MeSH Terms

Autoimmune Diseases*
Biomarkers
Epigenomics
Genomics
Metabolomics
Proteomics
Statistics as Topic
Systems Biology*
Translational Medical Research

Figure

  • Figure 1 Stages of autoimmune diseases. A variety of environmental factors and epigenetic changes in a genetically susceptible host trigger the initiation of autoimmune responses (trigger stage). The autoimmune response is activated by immune mediated attack against endogenous or exogenous self-antigens (preclinical stage). The duration of antigen exposure, impact of susceptible genes and/or epigenetic changes, and influence of effector function may dictate the phenotypic expression of AIDs (clinical stage).

  • Figure 2 Biomarker discovery of a specific Th subset. T cells are differentiated into functionally distinct phenotypes, and the T cell subtypes are analyzed by complementary transcriptomics and functional proteomics using mass spectrometry or gel chromatography. When candidate genes are recognized, their role in cellular functions can be studied using RNA interference. The chromatin immunoprecipitation (ChIP) method is used to investigate the interaction between transcription factors and genomic DNA and to identify genes putatively regulated by these factors.

  • Figure 3 Systems biology approaches for AIDs in combination with multi-OMICs and network analysis. The multiple 'omics' (multi-omics) approaches (e.g., genomics, transcriptomics, proteomics, and metabolomics), in combination with bioinformatics and biostatistics, have made it possible to accelerate the discovery and development of specific biomarkers for AIDs. The combination of the biologic approaches, known as systems biology, provides a network analysis of post-transcriptional regulation and cellular regulatory circuits, includeing transcriptional networks, signal pathways, protein-protein interaction, and metabolic pathways, in each specific cell subset at different stages of AIDs.


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