Andreas Beyer

FMNS | Institute for Genetics (UoC) & CMMC & CDS

Univ.-Prof. Dr. Andreas Beyer

Principal Investigator
Professor for systems biology and computational biology

+49 221 478 84429

andreas.beyer[at]uni-koeln.de

Website

AndreasBeyer012

Research Areas

Cellular Networks and Systems Biology

Modern biology creates enormous amounts of data. We are developing computational methods to turn this data into a mechanistic understanding of cell biology and disease processes.

Research Focus

The speed at which genes are copied (transcriptional speed) increases with age. This acceleration coincides with other perturbations such as DNA damage, which compromises RNA production and impacts on lifespan. See Debès et al. (2023) and Papadakis et al. (2023) for more. [Created with BioRender.com] — The speed at which genes are copied (transcriptional speed) increases with age. This acceleration coincides with other perturbations, such as DNA damage, which compromises RNA production and impacts on lifespan. See Debès et al. (2023) and Papadakis et al. (2023) for more.

A growing number of technologies allow for the genome-scale measurement of biological properties such as protein and mRNA concentrations or phenotypic changes (e.g. response to RNAi knock-downs). The genome-wide nature of the available data facilitates a systems perspective: it becomes possible to go beyond individual genes or pathways and to study regulatory processes of the entire system ‘cell’. However, up to now the potential is by far not being fully exploited.

Our group has adopted a network perspective by studying relationships between proteins and other biomolecules (e.g. DNA, RNA) in silico to reveal the regulatory context of relevant genes. During the past years, we contributed new computational methods for large-scale data integration, network biology, and statistical genetics. A tight network of experimental collaborators facilitates the experimental validation of our computational analysis.

Molecular systems biology is much more than ‘omics’ data analysis. It aims to develop a mechanistic understanding of cellular changes at a systems level.

Our Goals

Cells need to tightly control the concentration and state of mRNA and protein molecules to maintain homeostasis. Using systems-level approaches, we are investigating changes in regulatory and biosynthetic processes contributing to age-associated decline in mRNA and protein biosynthesis.

The Beyer group has made important contributions to further develop a range of biostatistical and bioinformatic methods, such as gene mapping techniques, network biology, and functional genomic screen analysis.
We have discovered that the speed of RNA polymerase II changes with age, which has negative consequences for the quality of the produced RNA.
Further, we have a great interest in the relationship between mRNA and protein amounts. Our work has yielded fundamental findings on the link between a protein’s function and the manner in which its concentration is regulated in the cell.

Recently we started to also consider protein states, e.g. protein phosphorylation and protein folding, using high-throughput proteomics methods. In order to reveal causes of age-associated phenotypes, we have developed computational methods to quantify different types of somatic mutations and transcriptional mistakes from single cell data. All of this is geared towards better understanding molecular and cellular mechanisms of human diseases like neurodegeneration, cancer, and chronic kidney disease.

Key Publications

Weith M, Großbach J, Clement-Ziza M, Gillet L, Rodríguez-López M, Marguerat S, Workman CT, Picotti P, Bähler J, Aebersold R, Beyer A (2023) Genetic effects on molecular network states explain complex traits. Mol Syst Biol. e11493. doi: 10.15252/msb.202211493.
Debès C*, Papadakis A*, Grönke S*, Karalay Ö*, Tain LS, Mizi A, Nakamura S, Hahn O, Weigelt C, Josipovic N, Zirkel A, Brusius I, Sofiadis K, Lamprousi M, Lu YX, Huang W, Esmaillie R, Kubacki T, Späth MR, Schermer B, Benzing T, Müller RU, Antebi A^#, Partridge L^#, Papantonis A^#, Beyer A^#. (2023) Ageing-associated changes in transcriptional elongation influence longevity. Nature. 616(7958):814-821. doi: 10.1038/s41586-023-05922-y.
Mackmull MT*, Nagel L*, Sesterhenn F, Muntel J, Grossbach J, Stalder P, Bruderer R, Reiter L, van de Berg WDJ, de Souza N, Beyer A^#, Picotti P^# (2022) Global, in situ analysis of the structural proteome in individuals with Parkinson's disease to identify a new class of biomarker. Nat. Struct. Mol. Biology. 29(10):978-989.
Charmpi K*, Guo T^#,*, Zhong Q^*, Wagner U^*, Sun R, Toussaint NC, Fritz CE, Yuan C, Chen H, Rupp NJ, Christiansen A, Rutishauser D, Rüschoff JH, Fankhauser C, Saba K, Poyet C, Hermanns T, Oehl K, Moore AL, Beisel C, Calzone L, Martignetti L, Zhang Q, Zhu Y, Rodríguez Martínez M, Manica M, Haffner MC, Aebersold R^#, Wild PJ^#, Beyer A^# (2020) Convergent network effects along the axis of gene expression during prostate cancer progression. Genome Biology 21(1):302. doi: 10.1186/s13059-020-02188-9.
Leote AC, Wu X, Beyer A (2022) Regulatory network-based imputation of dropouts in single-cell RNA sequencing data. PLoS Comput Biol. 18(2):e1009849.