Interdisziplinäres Zentrum
für Bioinformatik

Integrative mathematical modelling approaches

The Max Planck Institute for Mathematics in the Sciences (MIS) centres mathematical expertise enabling profound analyses of generation principles for the design of systems-biological models. This includes the fields of nonlinear dynamics, graph theory, and information theory (J. Jost). Various cooperations with biological partners were initiated, e.g. related to information theoretic analysis of gene expression and regulation pathways (K. Scherrer, Paris), information processing in the early auditory cortex (R. Rübsamen), reconstruction of signal transduction networks from gene expression data (F. Horn), and genetic representation of external information (M. Lachmann, Max Planck Institute for Evolutionary Anthropology). Furthermore, an internationally leading group for the development and application of rigorous mathematical multi-scale methods (relaxation, homogenisation, Gamma-convergence, hybrid analytical numerical methods) was built up by S. Müller. These methods can be exploited to address multi-scale problems in biology. In this field A. Stevens has a long term expertise including the passage from discrete and/or stochastic models on the single cell level to continuum models, as well as from mesoscopic dynamics to macroscopic descriptions. The new research group at MIS headed by N. Ay brings systematic expertise in information theory and other aspects of complex systems. Our expertise regarding mathematical modelling approaches is completed by the expertise of the IMISE in parametric modelling of chemotherapy effects and tumour growth as well as in pharmacokinetic/-dynamic modelling. Herein, we were able to successfully predicted a particular scheme for treatment of Hodgkin-(HL) and aggressive Non-Hodgkin Lymphoma patients that has been confirmed by clinical trials (Diehl et al. 2003, Pfreundschuh 2004) Furthermore, we have recently achieved a breakthrough in pharmakodynamic modelling of haematopoiesis recovery after chemotherapy. It could be demonstrated that a model of the granulopoietic system fits a large data set from many multi-centre oncological clinical trials. The model is predictive and can be used for optimising chemotherapy and supportive growth factor dosing and timing in the design of clinical trials (Engel et al. 2004, Scholz et al. 2005).

PDF-versions of publications are available at: IMISE

Diehl V, ...Löffler M. German Hodgkin's Lymphoma Study Group. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease. N Engl J Med. 2003;348(24):2386-95.
Engel C, Scholz M, Loeffler M. A computational model of human granulopoiesis to simulate the hematotoxic effects of multicycle polychemotherapy. Blood. 2004;104(8):2323-31.
Pfreundschuh M, ...Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL Blood. 2004;104(3):634-41 and Two-weekly:... results of the NHL-B1 trial of the DSHNHL. Blood. 2004;104(3):626-33.
Scholz M, Engel C, Löffler M. Model-based design of chemotherapeutic regimens that account for heterogeneity in leucopoenia Br. J. Haematol. 2006. 132(6), 723-735.
Scholz M, Engel C, Löffler M. Modelling human granulopoiesis under poly-chemotherapy with G-CSF support. J Math Biol. 2005;50(4):397-439.