Computational cancer biology

Cancer is a genetic disease caused by mutations to the genome. When such mutations hit critical genetic elements, they perturb cellular signalling resulting in overly proliferative cells. The availability of cheap sequencing technologies has led to large international efforts such as the International Cancer Genome Consortium for charting the genomic lesions leading to cancer. A revelation of these projects was an even greater genomic complexity of cancer genomes than previously anticipated: Despite having the same disease each patient harbours a unique constellation of mutations. The genetic complexity of cancer is a challenge and an opportunity at the same time. A challenge to understand the underlying mechanisms of cancer development - and an opportunity for finding an explanation for differences in therapy success and outcome.

Gerstung research 2015(a) Predicted risk and observed outcome in 1540 AML patients. (b) Personal constellation of genomic and clinical risk factors for 399 patients. Although there exist some recurrent similarities, each patient has a unique pattern of risk factors.

We have developed statistical models for relating different layers of genomic, molecular and clinical data to extract the precise connections among variables to understand the connection of genotype and phenotype. Moreover we have been working on biostatistical models and informatics tools for predicting outcome based on comprehensive high-dimensional data sets.

Another area of our research are the evolutionary dynamics of cancer. The process of developing cancer is driven by mutation and selection; hence the language to quantify that process is that of evolutionary dynamics. Deep sequencing unmasks the clonal composition of a cancer, which sheds some light on its evolutionary history. Accurate detection of subclonal mutations and reconstruction of phylogenies requires, however, accurate bioinformatics tools that we are actively developing.

Future projects and goals

Starting at the EBI in August 2015, we envisage installing a research programme covering different aspects of computational cancer biology. Part of this research will be conducted in local collaboration, and also within national and international initiatives. Future research will involve developing and deploying tools to decipher mutational signatures based on data of comprehensive screens of genotoxins and genetic repair deficiencies. We will continue developing bioinformatical methods for reconstructing the evolutionary history of cancer using NGS data from individual and multiple samples generated as part of international efforts. Lastly, we will work on statistical methods for data-driven personalised outcome predictions.

Selected publications

Experimental / computational fellowships

ESPOD postdoctoral programme

Interdisciplinary fellowships

EIPOD: Interdisciplinary postdoctoral fellowships at EMBL

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