Löffler-Wirth – Algorithms for complex data in life sciences

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FORMER MEMBERS OF THE GROUP

  • Dr. rer. nat. Lydia Hopp – Postdoc
  • Dr. med. Alexander Frenzel – Doctoral student
  • Milan Pentrack – Scientist
  • Thanh Hoang Le – Scientific Assistant
  • Verena Looser – Scientific Assistant
  • Clemens Malkawi – Scientific Assistant
  • Lena Richter – Scientific Assistant
  • Stephan Thönes – Master Student
  • Danja Zhupani – Student

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SHORT INTRODUCTION

We aim at discovering mechanisms of biological dysfunction in complex diseases by pursuing a systems view that includes molecular, cellular, tissue, organism and population level aspects.  Hereby we focus on the analysis and functional mining of large and heterogeneous data which includes different kinds of high throughput ‘OMICs’, phenotypic and clinical data.

In particular, we develop and implement bioinformatical algorithms suited for high-dimensional data. A central approach are self-organizing maps (SOMs), which are utilized to reduce the feature and sample space dimensions while preserving the information richness contained, and which we complemented with algorithms for preprocessing, data integration,  feature selection, function mining and visualization. Our R-package for holistic analysis of gene expression data can be downloaded from GitHub and Bioconductor repositories:

https://github.com/hloefflerwirth/oposSOM

http://master.bioconductor.org/packages/release/bioc/html/oposSOM.html

Additionally we develop methods to disentangle complex disease entities such as cancer subtypes, and to evaluate the interplay between activated/deactivated cellular functionalities and different disease stages. The latter one allows for the data driven staging of, e.g., cancer samples, and for the recapitulation of cancer progression.

Finally, modeling and simulation experiments supplement clinical data to track cancer progression trajectories. Our algorithms allow to generate a state space network for a given study and to investigate transition paths from healthy cells to diseased states, and from low grade to higher grade stadiums.

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RESEARCH SCOPE

  • Systems biology of cancer (lymphoma, glioma, melanoma & hereditary colon cancer): Analysis of omics data to develop a systems view on basal mechanisms of tumor genesis and progression
  • Analysis of body scanner data, evaluation of body types and association to diseases
  • Molecular phenotypes of the population of Leipzig
  • Trajectories in single cell differentiation experiments
  • Liquid biopsy analytics
  • Interactive analysis and diagnosis/prognosis support tools

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ASSOCIATED PROJECTS & PARTNER

  • BMBF funded Projects (MMML-MYC-SYS, HNPCC-SYS, CAP-SYS, Glioma-SYS)
  • LIFE – Leipzig Research Center for Civilization Diseases
  • German Glioma network
  • Hautklinik Leipzig
  • Max Planck Institute for Evolutionary Anthropology
  • IZI – Fraunhofer Institute for Cell Therapy and Immunology
  • Institute for transfusion medicine Leipzig
  • Charité Berlin
  • University College London

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SELECTED PUBLICATIONS

  • Loeffler-Wirth, H.*, Hopp, L. *, Schmidt, M., Zakharyan, R., Arakelyan, A. & Binder, H.: The transcriptome and methylome of the developing and aging brain and their relations to gliomas and psychological disorders. Cells 2022
  • Loeffler-Wirth, H., Reikowski, J., Hakobyan, S., Wagner, J. & Binder, H.: oposSOM-Browser: An interactive tool to explore omics data landscapes in health science. BMC Bioinformatics 2020
  • Schmidt, M., Hopp, L., Arakelyan, A., Kirsten, H., Engel, C., Wirkner, K., Krohn, K., Burkhardt, R., Thiery, J., Loeffler, M. & Loeffler-Wirth, H.* & Binder, H.*: The Human Blood Transcriptome in a Large Population Cohort and Its Relation to Aging and Health. Frontiers in Big Data 2020
  • Loeffler‐Wirth, H., Schmidt, M. & Binder, H.: Covid-19 trajectories: Monitoring pandemic in the worldwide context. Viruses 2020
  • Loeffler-Wirth, H., Kreuz, M., Hopp, L., Arakelyan, A., Haake, A., Cogliatti, S., Feller, A., Hansmann, M., Lenze, D., Möller, P., Müller-Hermelink, H., Fortenbacher, E., Willscher, E., Ott, G., Rosenwald, A., Pott, C., Schwaenen, C., Trautmann, H., Wessendorf, S., Stein, H., Szczepanowski, M., Trümper, L., Hummel, M., Klapper, W., Siebert, R., Loeffler, M. & Binder, H.: A modular transcriptome map of mature B-cell lymphomas. Genome Medicine 2019
  • Loeffler-Wirth, H., Binder, H., Willscher, E., Gerber, T. & Kunz, M.: Pseudotime dynamics in melanoma single-cell transcriptomes reveals different mechanisms of tumor progression. Biology 2018
  • Camp, G., Sekine, K., Gerber, T., Loeffler-Wirth, H., Binder, H., Gac, M., Kanton, S., Kageyama, J., Damm, G., Seehofer, D., Belicova, L., Zerial, M., Bickle, M., Barsacchi, R., Okuda, R., Yoshizawa, E., Kimura, M., Ayabe, H., Taniguchi, H., Takebe, T. & Treutlein, B.: Multilineage communication regulates human liver bud development from pluripotency. Nature 2017
  • Loeffler-Wirth, H., Willscher, E., Ahnert, P., Wirkner, K., Engel, C., Loeffler, M. & Binder, H.: Novel anthropometry based on 3D-bodyscans applied to a large population based cohort. PLOS ONE 2016
  • Löffler-Wirth, H., Kalcher, M. & Binder, H.: oposSOM: R-package for individualized analysis of genome-wide expression landscapes on Bioconductor. Bioinformatics 2015
  • Weller, M., Weber, R., Willscher, E., Riehmer, V., Hentschel, B., Kreuz, M., Felsberg, J., Beyer, U., Löffler-Wirth, H., Kaulich, K., Steinbach, J., Hartmann, C., Gramatzki, D., Schramm, J., Westphal, M., Schackert, G., Simon, M., Martens, T., Boström, J., Hagel, C., Sabel, M., Krex, D., Tonn, J., Wick, W., Noell, S., Schlegel, U., Radlwimmer, B., Pietsch, T., Löffler, M., von Deimling, A., Binder, H. & Reifenberger, G.: Molecular classification of diffuse cerebral WHO grade II/III gliomas using genome- and transcriptome-wide profiling improves stratification of prognostically distinct patient groups. Acta Neuropathologica 2015
  • Charbord, P., Pouget, C., Binder, H., Dumont, F., Stik, G., Levy, P., Allain, F., Marchal, C., Richter, J., Uzan, B., Pflumio, F., Letourneur, F., Wirth, H., Dzierzak, E., Traver, D., Jaffredo, T. & Durand, C.: A Systems Biology Approach for Defining the Molecular Framework of the Hematopoietic Stem Cell Niche. Cell stem cell 2014
  • Wirth, H.: Analyse molekularbiologischer Daten mittels Self-organizing Maps. Lecture Notes in Informatics (“Ausgezeichnete Informatikdissertationen 2012”) 2013
  • Hopp, L., Lembcke, K., Binder, H. & Wirth, H.: Portraying the Expression Landscapes of B-Cell Lymphoma – Intuitive Detection of Outlier Samples and of Molecular Subtypes. Biology 2013
  • Wirth, H., Löffler, M., von Bergen, M. & Binder, H.: Expression cartography of human tissues using self-organizing maps. BMC Bioinformatics 2011