Deep-Sequencing/Bioinformatics

Project Summary

A molecular understanding of disease mechanisms requires a global approach to the study of chromatin states and gene regulation. We will provide our infrastructure and expertise with deep-sequencing technologies to generate genome-wide maps of epigenetic modifications in various cell types. A dedicated data management centre will be further developed to facilitate access, visualization and routine analysis of genome-wide data. Our group will also offer regular training and help to improve the capacity for epigenetic research towards the development of potential epigenetic therapies.

Selected project-relevant publications

• Darkow E., Yusuf D., Rajamani S., Backofen R., Kohl P., Ravens U. and Peyronnet R. (2023) Meta-Analysis of Mechano-Sensitive Ion Channels in Human Hearts: Chamber- and Disease-Preferential mRNA Expression. Int J Mol Sci 24, doi 10.3390/ijms241310961.
• Akol I., Izzo A., Gather F., Strack S., Heidrich S., D Ó.H., Villarreal A., Hacker C., Rauleac T., Bella C., Fischer A., Manke T. and Vogel T. (2023) Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome. Proc Natl Acad Sci U S A 120, e2122467120.
• Kumar A., Cuccuru G., Grüning B. and Backofen R. (2022) An accessible infrastructure for artificial intelligence using a Docker-based JupyterLab in Galaxy. Gigascience 12, doi 10.1093/gigascience/giad1028.
• Grzejda D., Mach J., Schweizer J.A., Hummel B., Rezansoff A.M., Eggenhofer F., Panhale A., Lalioti M.E., Cabezas Wallscheid N., Backofen R., Felsenberg J. and Hilgers V. (2022) The long noncoding RNA mimi scaffolds neuronal granules to maintain nervous system maturity. Sci Adv 8, eabo5578.
• Bray S., Dudgeon T., Skyner R., Backofen R., Grüning B. and Von Delft F. (2022) Galaxy workflows for fragment-based virtual screening: a case study on the SARS-CoV-2 main protease. J Cheminform 14, 22.
• Videm P., Kumar A., Zharkov O., Grüning B.A. and Backofen R. (2021) ChiRA: an integrated framework for chimeric read analysis from RNA-RNA interactome and RNA structurome data. Gigascience 10, doi: 10.1093/gigascience/giaa1158.
• Lopez-Delisle L., Rabbani L., Wolff J., Bhardwaj V., Backofen R., Grüning B., Ramírez F. and Manke T. (2021) pyGenomeTracks: reproducible plots for multivariate genomic datasets. Bioinformatics 37, 422-423.
• Kumar A., Rasche H., Grüning B. and Backofen R. (2021) Tool recommender system in Galaxy using deep learning. Gigascience 10, doi: 10.1093/gigascience/giaa1152.
• Clapes T., Polyzou A., Prater P., Sagar, Morales-Hernández A., Ferrarini M.G., Kehrer N., Lefkopoulos S., Bergo V., Hummel B., Obier N., Maticzka D., Bridgeman A., Herman J.S., Ilik I., Klaeylé L., Rehwinkel J., Mckinney-Freeman S., Backofen R., Akhtar A., Cabezas-Wallscheid N., Sawarkar R., Rebollo R., Grün D. and Trompouki E. (2021) Chemotherapy-induced transposable elements activate MDA5 to enhance haematopoietic regeneration. Nat Cell Biol 23, 704-717.
• Wolff J., Rabbani L., Gilsbach R., Richard G., Manke T., Backofen R. and Grüning B.A. (2020) Galaxy HiCExplorer 3: a web server for reproducible Hi-C, capture Hi-C and single-cell Hi-C data analysis, quality control and visualization. Nucleic Acids Res 48, W177-w184.
• Uhl M., Tran V.D. and Backofen R. (2020) Improving CLIP-seq data analysis by incorporating transcript information. BMC Genomics 21, 894.
• Lopez-Delisle L., Rabbani L., Wolff J., Bhardwaj V., Backofen R., Grüning B., Ramírez F. and Manke T. (2020) pyGenomeTracks: reproducible plots for multivariate genomic data sets. Bioinformatics, doi: 10.1093/bioinformatics/btaa1692.
• Heyl F., Maticzka D., Uhl M. and Backofen R. (2020) Galaxy CLIP-Explorer: a web server for CLIP-Seq data analysis. Gigascience 9, doi: 10.1093/gigascience/giaa1108.
• Ferrari F., Arrigoni L., Franz H., Izzo A., Butenko L., Trompouki E., Vogel T. and Manke T. (2020) DOT1L-mediated murine neuronal differentiation associates with H3K79me2 accumulation and preserves SOX2-enhancer accessibility. Nat Commun 11, 5200.
• De Koning W., Miladi M., Hiltemann S., Heikema A., Hays J.P., Flemming S., Van Den Beek M., Mustafa D.A., Backofen R., Grüning B. and Stubbs A.P. (2020) NanoGalaxy: Nanopore long-read sequencing data analysis in Galaxy. Gigascience 9, doi: 10.1093/gigascience/giaa1105.
• Bhardwaj V., Semplicio G., Erdogdu N.U., Manke T. and Akhtar A. (2019) MAPCap allows high-resolution detection and differential expression analysis of transcription start sites. Nat Commun 10, 3219.
• Wolff J., Bhardwaj V., Nothjunge S., Richard G., Renschler G., Gilsbach R., Manke T., Backofen R., Ramirez F. and Gruning B.A. (2018) Galaxy HiCExplorer: a web server for reproducible Hi-C data analysis, quality control and visualization. Nucleic Acids Res 46, W11-w16.
• Ramirez F., Bhardwaj V., Arrigoni L., Lam K.C., Gruning B.A., Villaveces J., Habermann B., Akhtar A. and Manke T. (2018) High-resolution TADs reveal DNA sequences underlying genome organization in flies. Nat Commun 9, 189.
• Maticzka D., Ilik I.A., Aktas T., Backofen R. and Akhtar A. (2018) uvCLAP is a fast and non-radioactive method to identify in vivo targets of RNA-binding proteins. Nat Commun 9, 1142.
• Gilsbach R., Schwaderer M., Preissl S., Gruning B.A., Kranzhofer D., Schneider P., Nuhrenberg T.G., Mulero-Navarro S., Weichenhan D., Braun C., Dressen M., Jacobs A.R., Lahm H., Doenst T., Backofen R., Krane M., Gelb B.D. and Hein L. (2018) Distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart in vivo. Nat Commun 9, 391.
• Costa F., Grun D. and Backofen R. (2018) GraphDDP: a graph-embedding approach to detect differentiation pathways in single-cell-data using prior class knowledge. Nat Commun 9, 3685.
• Arrigoni L., Al-Hasani H., Ramirez F., Panzeri I., Ryan D.P., Santacruz D., Kress N., Pospisilik J.A., Bonisch U. and Manke T. (2018) RELACS nuclei barcoding enables high-throughput ChIP-seq. Commun Biol 1, 214.
• Batut B., Hiltemann S., Bagnacani A., Baker D., Bhardwaj V., Blank C., Bretaudeau A., Brillet-Gueguen L., Cech M., Chilton J., Clements D., Doppelt-Azeroual O., Erxleben A., Freeberg M.A., Gladman S., Hoogstrate Y., Hotz H.R., Houwaart T., Jagtap P., Lariviere D., Le Corguille G., Manke T., Mareuil F., Ramirez F., Ryan D., Sigloch F.C., Soranzo N., Wolff J., Videm P., Wolfien M., Wubuli A., Yusuf D., Taylor J., Backofen R., Nekrutenko A. and Gruning B. (2018) Community-Driven Data Analysis Training for Biology. Cell Syst 6, 752-758.e751.
• Ramirez F., Bhardwaj V., Arrigoni L., Lam K.C., Gruning B.A., Villaveces J., Habermann B., Akhtar A. and Manke T. (2018) High-resolution TADs reveal DNA sequences underlying genome organization in flies. Nat Commun 9, 189.
• Gruning B.A., Fallmann J., Yusuf D., Will S., Erxleben A., Eggenhofer F., Houwaart T., Batut B., Videm P., Bagnacani A., Wolfien M., Lott S.C., Hoogstrate Y., Hess W.R., Wolkenhauer O., Hoffmann S., Akalin A., Ohler U., Stadler P.F. and Backofen R. (2017) The RNA workbench: best practices for RNA and high-throughput sequencing bioinformatics in Galaxy. Nucleic Acids Res 45, W560-w566.
• Castex J., Willmann D., Kanouni T., Arrigoni L., Li Y., Friedrich M., Schleicher M., Wohrle S., Pearson M., Kraut N., Meret M., Manke T., Metzger E., Schule R. and Gunther T. (2017) Inactivation of Lsd1 triggers senescence in trophoblast stem cells by induction of Sirt4. Cell Death Dis 8, e2631.
• Aktas T., Avsar Ilik I., Maticzka D., Bhardwaj V., Pessoa Rodrigues C., Mittler G., Manke T., Backofen R. and Akhtar A. (2017) DHX9 suppresses RNA processing defects originating from the Alu invasion of the human genome. Nature 544, 115-119.
• Ramírez F., Ryan D.P., Grüning B., Bhardwaj V., Kilpert F., Richter A.S., Heyne S., Dündar F. and Manke T. (2016) deepTools2: a next generation web server for deep-sequencing data analysis.  Nucl. Acids Res, doi: 10.1093/nar/gkw257
• Kranzhofer D.K., Gilsbach R., Gruning B.A., Backofen R., Nuhrenberg T.G. and Hein L. (2016) 5′-Hydroxymethylcytosine Precedes Loss of CpG Methylation in Enhancers and Genes Undergoing Activation in Cardiomyocyte Maturation. PLoS One 11, e0166575.
• Hoppmann A.S., Schlosser P., Backofen R., Lausch E. and Kottgen A. (2016) GenToS: Use of Orthologous Gene Information to Prioritize Signals from Human GWAS. PLoS One 11, e0162466.
• Duteil D., Tosic M., Lausecker F., Nenseth H.Z., Muller J.M., Urban S., Willmann D., Petroll K., Messaddeq N., Arrigoni L., Manke T., Kornfeld J.W., Bruning J.C., Zagoriy V., Meret M., Dengjel J., Kanouni T. and Schule R. (2016) Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue. Cell Rep 17, 1008-1021.
• Chlamydas S., Holz H., Samata M., Chelmicki T., Georgiev P., Pelechano V., Dundar F., Dasmeh P., Mittler G., Cadete F.T., Ramirez F., Conrad T., Wei W., Raja S., Manke T., Luscombe N.M., Steinmetz L.M. and Akhtar A. (2016) Functional interplay between MSL1 and CDK7 controls RNA polymerase II Ser5 phosphorylation. Nat Struct Mol Biol 23, 580-589.