S. Alice Long1 and Peter S. Linsley2 1Center for Translational Immunology, Benaroya Research Institute, Seattle, Washington 98101, USA 2Center for Systems Immunology, Benaroya Research Institute, Seattle, Washington 98101, USA Correspondence: alongbenaroyaresearch.org; plinsleybenaroyaresearch.org

Biomarkers are critical to the staging and diagnosis of type 1 diabetes (T1D). Functional biomarkers offer insights into T1D immunopathogenesis and are often revealed using “omics” approaches that integrate multiple measures to identify involved pathways and functions. Application of the omics biomarker discovery may enable personalized medicine approaches to circumvent the more recently appreciated heterogeneity of T1D progression and treatment. Use of omics to define functional biomarkers is still in its early years, yet findings to date emphasize the role of cytokine signaling and adaptive immunity in biomarkers of progression and response to therapy. Here, we share examples of the use of omics to define functional biomarkers focusing on two signatures, T-cell exhaustion and T-cell help, which have been associated with outcomes in both the natural history and treatment contexts.