Bioinformatics and Computational Genomics
Genome-wide association studies have discovered many genetic variants associated with immune-mediated diseases, but can only explain the differences to a limited extent. Epigenetic changes in response to environmental influences could also contribute to disease susceptibility.
How do genetic background, epigenetic variation and environment together influence immune function and disease development? At which genetic site? What mechanisms do they act on and how do they work? These are questions that Prof. Dr. Cheng-Jian Xu and his team are trying to answer using bioinformatics and computational genomics.
The MHH research group is part of the developing CiiM and is currently based at TWINCORE in Hannover.
The group focuses on the development and application of computational approaches to better understand immune functions, in particular the contribution of epigenetic changes to these pathophysiological conditions. For this, samples from cohort studies are analysed using epigenetic whole genome profiling, novel single cell technologies and systems genetics approaches. The aim is to develop customised therapy strategies based on detailed molecular stratification of disease subgroups - an important step towards individualised medicine.
Epigenetics of RSV infection and allergic diseases
Epigenetic signatures can shed light on the mechanisms of allergic diseases and infections. Recently, the study of our large epigenetic cohort has shown the association between asthma susceptibility and antiviral immunity in early life. Respiratory syncytial virus (RSV) infection in early life is associated with an increased prevalence of wheezing in early childhood and may also influence the long-term development of asthma and allergies. How RSV infection in infancy, when the immune system is immature, would affect the host immune system in the long term and how this would affect the development of asthma and allergic disease remains unknown. We hypothesised that RSV infection in early life causes changes in DNA methylation in the epithelium of the nasal passages during childhood. To test this hypothesis, we examined the MAKI randomised clinical trial to find the direct association between RSV prophylaxis in infancy and DNA methylation changes in nasal epithelium at age 6 years.
Cooperation partners: Prof Louis Bont (UMC Utrecht, Netherlands) and Prof Gerard Koppelman (UMC Groningen, Netherlands)
Allergy risk prediction through cross-omics deep learning
Although many genes and environmental factors have been identified that are associated with allergy risk, it is not yet possible to cure allergies. In this project, the team is using a hugely growing amount of cross-omics data (genomics, epigenomics and transcriptomics, etc.) and the latest artificial intelligence (AI) techniques to predict the risk of diseases such as allergies. By integrating cross-omics data using a Bayesian causal inference method, a more comprehensive network can be built to paint a more complete picture of the molecular process underlying the physiological condition. The AI predictive model facilitates the identification of the major factors contributing to allergy. It can also lead to the development of new clinical applications for the diagnosis of high-risk patients, an important step for personalised medicine.
Cooperation partners: Prof Gerard Koppelman (UMC Groningen, Netherlands) and Dr Marnix Bügel (Micompany, Netherlands)
Until the building is completed, the group is based at TWINCORE. You can therefore find the current team list here.
Xu, C.-J, Söderhäll, C, Bustamante, et al. DNA methylation in childhood asthma: an epigenome-wide meta-analysis. Lancet Respiratory Medicine 2018, 6, 379–388 (IF 23)
Qi, C., ..., Xu C-J+,Koppelman GH+, Nasal DNA methylation profiling of asthma and rhinitis. Journal of Allergy and Clinical Immunology 2020, in press https://doi.org/10.1016/j.jaci.2019.12.911 . (+equal contribution as last authors) (IF 14)
Reese SE+, Xu C-J+, den Dekker HT+, et al. Epigenome-wide meta-analysis of DNA methylation and childhood asthma.Journal of Allergy and Clinical Immunology 2019. 143, 2062-2074 (+equal contribution as first authors) (IF 14)
Forno E, Wang T, Qi C, Yan Q, Xu C-J, Boutaoui N, et al. DNA methylation in nasal epithelium, atopy, and atopic asthma in children: a genome-wide study. The Lancet Respiratory Medicine. 2018, 7, 336-346, (IF 23)
Gruzieva, O, Xu, C.-J, Breton, CV, et.al,. Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure. Environmental Health Perspective. 2017,125, 104–110. (IF 8)
A complete list of Cheng-Jian Xu's publications can be found on Google Scholar.
The Group "Bioinformatics and computational genomics" is seeking a Postdoctoral researcher in the area of multi-omics integration to prediction immune response to infection. For further information please refer to the advertisement. Please send your application referring to the code 71/2020 via E-Mail to JobsHZI@helmholtz-hzi.de.
Furthermore, we are always happy to receive applications from candidates for a PhD project or a Postdoc position.
We also continuously offer Master/Bachelor Research projects. Please contact us viaE-Mail for further information.
For further questions please contact Xu.Chengjian@mh-hannover.de.