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Computational Genomics and System Genetics

Division of Computational Genomics and Systems Genetics

Prof. Dr. Oliver Stegle

Illustration of a statistical method for integrating multiple omics datasets. Multi?Omics Factor Analysis (MOFA) is a computational framework for unsupervised discovery of the principal axes of biological and technical variation when multiple omics assays are applied to the same samples.

Our interest lies in computational methods to unravel the genotype–phenotype map on a genome-wide scale. How do genetic background and environment jointly shape phenotypic traits or causes diseases? How are genetic and external factors integrated at different molecular layers, and how variable are molecular states between individual cells?
We use statistics and machine learning as our main tool to address these questions. To make accurate inferences from high-dimensional omics datasets, it is essential to account for biological and technical noise and to propagate evidence strength between different steps in the analysis. We develop methods that enable connecting genetic factors to phenotypes and to integrate multiomics data in health and disease.
Our methodological work ties in with biomedical collaborations, and we are developing methods to fully exploit high-throughput datasets from the most recent profiling technologies. In doing so, we derive computational methods to dissect phenotypic variability at the level of the transcriptome and the proteome and we derive new tools for single-cell biology.

Future Outlook
We will continue to develop innovative statistical approaches to analyse data from high-throughput genetic and molecular profiling studies. We are particularly interested in following up our recent efforts to model single-cell variation data. A major challenge in this field will be the integration of multiple data modalities in the same cells, for example linking single-cell epigenome variation with single-cell transcriptomes. We will carry out this work as an active partner in the Human Cell Atlas project (


Prof. Dr. Oliver Stegle
Computational Genomics and Systems Genetics (B260)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg

Selected Publications

  • Kleshchevnikov, V., Shmatko, A., Dann, E., Aivazidis, A., King, H. W., Li, T., ..., Stegle, O. , Bayraktar, O. A.. Cell2location maps fine-grained cell types in spatial transcriptomics (2022), Nature biotechnology, 40(5), 661-671. [cited: 108]
  • Velten, B., Braunger, J.M., Argelaguet, R., Arnol, D., Wirbel, J., Bredikhin, D., Zeller, G., Stegle, O. Identifying temporal and spatial patterns of variation from multimodal data using MEFISTO (2022). Nature methods, pp.1-8. [cited: 22]
  • Jerber, J., Seaton, D.D.#, Cuomo, A.S.#, Kumasaka, N., ...(9 additional authors) ..., Marioni, J.C., Merkle, F.T.@, Gaffney, DJ., Stegle, O. Population-scale single-cell RNA-seq profiling across dopaminergic neuron differentiation (2021). Nature Genetics, 53(3), 304-312. [cited: 80]
  • Bonder, M.J., Craig, S., Gloudemans, M.J., Frésard, L., Jakubosky, D., D'Antonio, Xin Li, X., ... (12 additional authors) ..., Montgomery, S.B., Stegle, O. Systematic assessment of regulatory effects of human disease variants in pluripotent cells (2021), Nature Genetics, 53.3: 313-321. [cited: 31]
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