Many studies have assessed inter-individual variability among human immune responses, Recent studies from the Human Functional Genomics Project (HFGP) have successfully characterized the impact of genetic and environmental factors on immune response in health. However, how epigenetic modification affects this variability related to the immune response is largely unknown. Epigenetic modification, e.g. DNA methylation, allows fully differentiated somatic cells to adapt gene expression to external stimuli in a long-term manner. An individual’s DNA methylation profile in response to infection could have a specific biological role in innate immune memory, and methylation change may act as primed enhancers potentially allowing for a faster response to a secondary infection.
This project will use vaccination in vivo stimulation to understand the epigenetic mechanism of the immune response to infection. The hypothesis is that the in vivo immune response to vaccination is regulated by the interaction of genetics and epigenetic status of immune cells.
Although many genes and environmental factors have been identified to associate with allergy risk, it is not yet possible to cure allergy diseases. In this project, the team uses an enormous growing amount of cross-omics data (genomics, epigenomics and transcriptomics etc) and latest artificial intelligence (AI) techniques to predict the risk of disease, such as allergy. By integrating cross-omics data, using a Bayesian causal inference method, a more comprehensive network can be constructed to paint a more complete picture of the molecular process underlying the physiological state. The prediction model from AI makes it easier to identify the most important factors that contribute to allergy. It can also lead to the development of new clinical applications to diagnose high-risk patients, a key step for personalized medicine.
Prof. Gerard Koppelman (UMC Groningen, Netherlands) and Dr. Marnix Bügel (Micompany, Netherlands)
Epigenetic regulation of immune response to infection
Xu CJ, Soderhall C, Bustamante M, Baiz N, Gruzieva O, Gehring U, Mason D, Chatzi L, Basterrechea M, Llop S, Torrent M, Forastiere F, Fantini MP, Carlsen KCL, Haahtela T, Morin A, Kerkhof M, Merid SK, van Rijkom B, Jankipersadsing SA, Bonder MJ, Ballereau S, Vermeulen CJ, Aguirre-Gamboa R, de Jongste JC, Smit HA, Kumar A, Pershagen G, Guerra S, Garcia-Aymerich J, Greco D, Reinius L, McEachan RRC, Azad R, Hovland V, Mowinckel P, Alenius H, Fyhrquist N, Lemonnier N, Pellet J, Auffray C, Consortium B, van der Vlies P, van Diemen CC, Li Y, Wijmenga C, Netea MG, Moffatt MF, Cookson W, Anto JM, Bousquet J, Laatikainen T, Laprise C, Carlsen KH, Gori D, Porta D, Iniguez C, Bilbao JR, Kogevinas M, Wright J, Brunekreef B, Kere J, Nawijn MC, Annesi-Maesano I, Sunyer J, Melen E, Koppelman GH (2018) DNA methylation in childhood asthma: an epigenome-wide meta-analysis. Lancet Respir Med 6(5): 379-388.
Qi, C., Jiang, Y., Yang, I. V., Forno, E., Wang, T., Vonk, J. M., Gehring, U., Smit, H. A., Milanzi, E. B., Carpaij, O. A., Berg, M., Hesse, L., Brouwer, S., Cardwell, J., Vermeulen, C. J., Acosta-Pérez, E., Canino, G., Boutaoui, N., van den Berge, M., Teichmann, S. A., Nawijn, M. C., Chen, W., Celedón, J. C., Xu, C.-J. & Koppelman, G. H. Nasal DNA methylation profiling of asthma and rhinitis. Journal of Allergy and Clinical Immunology 145, 1655–1663 (2020).
Allergy risk prediction through deep learning of cross-omics
Xu CJ, Bonder MJ, Soderhall C, Bustamante M, Baiz N, Gehring U, Jankipersadsing SA, van der Vlies P, van Diemen CC, van Rijkom B, Just J, Kull I, Kere J, Anto JM, Bousquet J, Zhernakova A, Wijmenga C, Annesi-Maesano I, Sunyer J, Melen E, Li Y, Postma DS, Koppelman GH (2017) The emerging landscape of dynamic DNA methylation in early childhood. BMC Genomics 18(1): 25.
Forno E, Wang T, Qi C, Yan Q, Xu CJ, Boutaoui N, Han YY, Weeks DE, Jiang Y, Rosser F, Vonk JM, Brouwer S, Acosta-Perez E, Colon-Semidey A, Alvarez M, Canino G, Koppelman GH, Chen W, Celedon JC (2019) DNA methylation in nasal epithelium, atopy, and atopic asthma in children: a genome-wide study. Lancet Respir Med 7(4): 336-346.