Biomedical Genomics

The Biomedical Genomics Group works on deepening the understanding of the functioning of the genome in relation to disease. We apply computational methods to determine genetic and genomic causes of disease and reversely also study the effects of the disease on the genome. For our studies, we use data from diverse sources which allows us to leverage our own data together with other data. Combining multiple different levels of omics data such as genomics, epigenomics, transcriptomics, proteomics and metabolomics provides an additional layer from which to extract insights. We also focus on techniques for multi-omic analysis as these still require the development of suitable analytical approaches put on robust statistical footing. Our focus is on three classes of diseases: 1) Cancer, 2) Rare diseases, and 3) Barrier diseases (asthma, COPD, and inflammatory bowel disease).

• Cancer: Our main effort here continues to be studying somatic mutation across a multitude of different kinds of cancer with the objective to identify mechanisms shared by different types of cancer and mechanisms that are unique to certain cancers. We have concluded our work in Quality Control working group of the ICGC-PanCancer study and delivered a quality framework and assessment of the over 2700 cancer genomes of this study. Our downstream analysis of the somatic mutations in these 2700 cancer genomes has given some highly interesting insights into the relationship of certain types of mutations, the tissue of origin of a cancer, and pan-cancer classes of cancers, such a microsatellite instable or immunoglobulin hyper-mutating tumours. We are now extending to larger collections of cancer genomes.
• Rare Disease: In rare diseases, we have been concentrating on the RD-Connect project and data. In order to sustain the RD-Connect legacy we established the RD-Connect Community.
• Barrier diseases: In respiratory disorders, we have been investigating the manifestation of genomic alterations and their relation to gene expression and clinical phenotypes with a particular focus on the presentation of early signs of known and potentially causal genomic events.

M. Duruisseaux et al.
“Epigenetic prediction of response to anti-PD-1 treatment in non-small-cell lung cancer: a multicentre, retrospective analysis.”
The Lancet Respiratory Medicine, 6(10):771, 2018.

L. Grassi et al.
“Dynamics of transcription regulation in human bone marrow myeloid differentiation to mature blood neutrophils.”
Cell Reports, 24(10):2784, 2018.

A. A.Singh et al.
“Multi-omics profiling reveals a distinctive epigenome signature for high-risk acute promyelocytic leukemia.”
Oncotarget, 9(39):25647, 2018.

T. Gstrein et al.
“Mutations in Vps15 perturb neuronal migration in mice and are associated with neurodevelopmental disease in humans.”
Nature Neuroscience, 21(2):207, 2018.

D. Owen et al.
“Recessive variants of MuSK are associated with late onset CMS and predominant limb girdle weakness.”
American Journal of Medical Genetics Part A, 176(7):1594, 2018.