Cancer Genomics / Transcriptomics
The lab was and is an active contributor to several international cancer research consortia, including The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). Our research mainly focuses on investigating aberrations in transcriptional regulation, specifically alternative splicing, and its relationship to underlying alterations of the somatic genotype. We employ techniques from statistical genetics and modern machine learning to identify loci that have a potentially causative effect and drive cancer progression [1]. Further, the group derives models from describing tumor evolution and assessing tumor heterogeneity.
We generate compendia of molecular phenotypes based on RNA-Seq data, including expression measurements and characterization of alternative splicing events [1]. Statistical methods are employed to find genes that show significant differences between tumor and normal populations and to explain functional consequences mechanistically [2]. We are particularly interested in gaining biological insights about splicing mechanisms in cancer and technical insights into understanding the effect of heterogeneity and clonal evolution on association analysis [1].
Lastly, we strongly emphasize reproducibility and automation of our analysis procedures. In the context of the ICGC PCAWG [3] and ICGC ARGO projects, we are members of the technical teams that design and implement analysis workflows in a robust and reproducible manner.
Involved group members: Andre Kahles, Kjong Lehmann (alumnus), Natalie Davidson (alumna), Gunnar Rätsch
References
[1] Kahles, André, Kjong-Van Lehmann, Nora C. Toussaint, Matthias Hüser, Stefan G. Stark, Timo Sachsenberg, Oliver Stegle et al. "Comprehensive analysis of alternative splicing across tumors from 8,705 patients." Cancer cell 34, no. 2 (2018): 211-224.
[2] Hirano, Satoshi, Lixing Yang, Malene Juul, Colin A. Purdie, Brian Patrick O'Neill, Rolf Kabbe, Elli Papaemmanuil et al. "Pan-cancer analysis of whole genomes." Nature 578, no. DKFZ-2020-01051 (2020): 82-93.
[3] Calabrese, Claudia, Natalie R. Davidson, Deniz Demircioğlu, Nuno A. Fonseca, Yao He, André Kahles, Kjong-Van Lehmann et al. "Genomic basis for RNA alterations in cancer." Nature 578, no. 7793 (2020): 129-136.