Cédric R. Weber, Teresa Rubio, Longlong Wang, Wei Zhang, Philippe A. Robert, Rahmad Akbar, Igor Snapkov, Jinghua Wu, Marieke L. Kuijjer, Sonia Tarazona, Ana Conesa, Geir K. Sandve, Xiao Liu, Sai T. Reddy, Victor Greiff, Helmsley Charitable Trust, European Commission, Research Council of Norway, Norwegian Cancer Society, University of Oslo, Weber, Cédric R. [0000-0003-4802-8996], Rubio, Teresa [0000-0003-0707-9244], Wang, Longlong [0000-0002-6508-1804], Zhang, Wei [0000-0002-6968-6974], Robert, Philippe A. [0000-0003-1345-5015], Akbar, Rahmad [0000-0002-6692-0876], Snapkov, Igor [0000-0001-5341-685X], Kuijjer, Marieke L. [0000-0001-6280-3130], Tarazona, Sonia [0000-0001-5346-1407], Conesa, Ana [0000-0001-9597-311X], Sandve, Geir K. [0000-0002-4959-1409], Liu, Xiao [0000-0002-8073-0534], Reddy, Sai T. [0000-0002-9177-0857], Greiff, Victor [0000-0003-2622-5032], Weber, Cédric R., Rubio, Teresa, Wang, Longlong, Zhang, Wei, Robert, Philippe A., Akbar, Rahmad, Snapkov, Igor, Kuijjer, Marieke L., Tarazona, Sonia, Conesa, Ana, Sandve, Geir K., Liu, Xiao, Reddy, Sai T., and Greiff, Victor
B- and T-cell receptor (immune) repertoires can represent an individual’s immune history. While current repertoire analysis methods aim to discriminate between health and disease states, they are typically based on only a limited number of parameters (e.g., clonal diversity, germline usage). Here, we introduce immuneREF: a quantitative multi-dimensional measure of adaptive immune repertoire (and transcriptome) similarity that allows interpretation of immune repertoire variation by relying on both repertoire features and cross-referencing of simulated and experimental datasets. immuneREF is implemented in an R package and was validated based on detection sensitivity of immune repertoires with known similarities and dissimilarities. To quantify immune repertoire similarity landscapes across health and disease, we applied immuneREF to >2400 datasets from individuals with varying immune states (healthy, [autoimmune] disease and infection [Covid-19], immune cell population). Importantly we discovered, in contrast to the current paradigm, that blood-derived immune repertoires of healthy and diseased individuals are highly similar for certain immune states, suggesting that repertoire changes to immune perturbations are less pronounced than previously thought. In conclusion, immuneREF implements population-wide analysis of immune repertoire similarity and thus enables the study of the adaptive immune response across health and disease states., Support was provided from The Helmsley Charitable Trust (#2019PG-T1D011, to VG), UiO WorldLeading Research Community (to VG), UiO:LifeSciences Convergence Environment Immunolingo (to VG and GKS), EU Horizon 2020 iReceptorplus (#825821) (to VG), a Research Council of Norway FRIPRO project (#300740, to VG), a Research Council of Norway IKTPLUSS project (#311341, to VG and GKS), a Norwegian Cancer Society grant (#215817, to VG), and Stiftelsen Kristian Gerhard Jebsen (K.G. Jebsen Coeliac Disease Research Centre) (to GKS), Swiss National Science Foundation (Project 31003A to S.T.R), the Norwegian Research Council, Helse Sør-Øst, and the University of Oslo through the Centre for Molecular Medicine Norway (#187615 to MLK).