@inproceedings{ManciniMariMassinietal.2018, author = {Mancini, Toni and Mari, Federico and Massini, Annalisa and Melatti, Igor and Salvo, Ivano and Sinisi, Stefano and Tronci, Enrico and Ehrig, Rainald and R{\"o}blitz, Susanna and Leeners, Brigitte}, title = {Computing Personalised Treatments through In Silico Clinical Trials. A Case Study on Downregulation in Assisted Reproduction}, booktitle = {Experimental Evaluation of Algorithms for Solving Problems with Combinatorial Explosion, Workshop of the Federated Logic Conference 2018 (FLoC 2018), Oxford}, doi = {10.29007/g864}, pages = {1 -- 16}, year = {2018}, abstract = {In Silico Clinical Trials (ISCT), i.e., clinical experimental campaigns carried out by means of computer simulations, hold the promise to decrease time and cost for the safety and efficacy assessment of pharmacological treatments, reduce the need for animal and human testing, and enable precision medicine. In this paper we present a case study aiming at quantifying, by means of a multi-arm ISCT supervised by intelligent search, the potential impact of precision medicine approaches on a real pharmacological treatment, namely the downregulation phase of a complex clinical protocol for assisted reproduction.}, language = {en} } @inproceedings{LangePloentzkeSchaeferetal.2016, author = {Lange, Alexander and Pl{\"o}ntzke, Julia and Sch{\"a}fer, Stefan and R{\"o}blitz, Susanna}, title = {Follicular maturation in cows: mathematical models and data}, booktitle = {10. European Conference on Mathematical and Theoretical Biology}, year = {2016}, language = {en} } @inproceedings{SchaeferPloentzkeRoeblitz2016, author = {Sch{\"a}fer, Stefan and Pl{\"o}ntzke, Julia and R{\"o}blitz, Susanna}, title = {Mathematical Modelling of Follicular Maturation in Cows and Women}, booktitle = {49. Jahrestagung der Physiologie und Pathologie der Fortpflanzung und gleichzeitig 41. Veterin{\"a}r-Humanmedizinische Gemeinschaftstagung 2016, Leipzig.}, year = {2016}, language = {en} } @inproceedings{IgdeWoelkRoeblitzetal.2015, author = {Igde, Sinaida and W{\"o}lk, Hendrik and R{\"o}blitz, Susanna and Reidelbach, Marco and Weber, Marcus and Hartmann, Laura}, title = {Identifying Multivalent Binding Kinetics of Precision Glycomacromolecules: A Kinetic Study Using kinITC}, booktitle = {M{\"u}nster Symposium on Cooperative Effects 2015 - SFB 858, at Westf{\"a}lische Wilhelms-Universit{\"a}t M{\"u}nster, 2015}, year = {2015}, abstract = {Multivalent sugar/protein interactions are well-known to proceed through different binding modes 1-5 which in turn can be described by their binding kinetics 3-5. This study provides additional insight into the association and dissociation reaction rates of complex multivalent sugar/protein interactions. Binding kinetics of recently introduced multivalent precision glycomacromolecules 6-8 to Concanavalin A (Con A) were studied by " kinetic Isothermal Titration Calorimetry " (kinITC) 9-11. The effect of multivalency is evaluated by comparing rate constants of glycomacromolecules obtaining the same and different valency of mannose ligands and by variation of the overall backbone properties, such as hydrophilic/ hydrophoboc. In addition, binding kinetics were studied using different conformations of Con A (homodimer vs.-tetramer) and thus a different protein valency. Our results show that precision glycomacromolecule/Con A binding proceeds non-cooperatively. Further, association and dissociation rates are mainly described by intermolecular complex formation. Together with the so-called functional valency, we can discriminate between " bound " and " unbound " states for macroscopic on-and off-rates, even for such complex glycooligomer/protein systems. By comparing e.g. a mono-to a divalent glycomacromolecule for their binding to dimeric Con A, we see a lower dissociation rate for the latter. As both bind monovalently to Con A, this is a strong indication for a statistical rebinding event. Further, there is a strong dependence of multivalent binding kinetics on the ligand density of glycomacromolecules as well as the Con A conformation and thus the overall on-and off-rates.}, language = {en} } @inproceedings{EhrigDierkesSchaeferetal.2016, author = {Ehrig, Rainald and Dierkes, Thomas and Sch{\"a}fer, Stefan and R{\"o}blitz, Susanna and Tronci, Enrico and Mancini, Toni and Salvo, Ivano and Alimguzhin, Vadim and Mari, Federico and Melatti, Igor and Massini, Annalisa and Kr{\"u}ger, Tillmann H. C. and Egli, Marcel and Ille, Fabian and Leeners, Brigitte}, title = {An integrative approach for model driven computation of treatments in reproductive medicine}, booktitle = {BIOMAT - Proceedings of the 15th International Symposium on Mathematical and Computational Biology, Rorkee, India}, year = {2016}, language = {en} } @inproceedings{PloentzkeBergStoetzeletal.2015, author = {Pl{\"o}ntzke, Julia and Berg, Mascha and St{\"o}tzel, Claudia and R{\"o}blitz, Susanna}, title = {A systems biology approach to bovine fertility and metabolism: Introduction of a glucose insulin model}, booktitle = {15th International Symposium on Mathematical and Computational Biology, Rorkee, India}, year = {2015}, language = {en} } @inproceedings{ManciniSalvoMarietal.2014, author = {Mancini, Toni and Salvo, Ivano and Mari, Federico and Melatti, Igor and Massini, Annalisa and Sinisi, Stefano and Tronci, Enrico and Davi, Francesco and Dierkes, Thomas and Ehrig, Rainald and R{\"o}blitz, Susanna and Leeners, Brigitte and Kr{\"u}ger, Tillmann H. C. and Egli, Marcel and Ille, Fabian}, title = {Patient-Specific Models from Inter-Patient Biological Models and Clinical Records}, booktitle = {Proceedings of the 14th Conference on Formal Methods in Computer-Aided Design (FMCAD 2014)}, pages = {207 -- 214}, year = {2014}, language = {en} } @inproceedings{GuptaKrauseRikeitetal.2014, author = {Gupta, Pooja and Krause, Carola and Rikeit, Paul and R{\"o}blitz, Susanna and Knaus, Petra and Sch{\"u}tte, Christof}, title = {Modeling of the BMP mediated co-regulation of the Smad and Non-Smad pathways in the context of cell density}, booktitle = {10th International BMP conference, 2014, Berlin, Germany}, year = {2014}, language = {en} } @inproceedings{YousefianDonatiSikorskietal.2026, author = {Yousefian, Maryam and Donati, Luca and Sikorski, Alexander and Weber, Marcus and R{\"o}blitz, Susanna}, title = {Exploring Metastable Dynamics of Gene Regulatory Networks with ISOKANN}, volume = {15959}, booktitle = {Computational Methods in Systems Biology. CMSB 2025}, doi = {10.1007/978-3-032-01436-8_8}, pages = {126 -- 149}, year = {2026}, abstract = {Stochastic dynamical systems like gene regulatory networks (GRNs) often exhibit behavior characterized by metastable sets (representing cellular phenotypes), in which trajectories remain for long times, whereas switches between these sets in the phase space are rare events. One way to capture these rare events is to infer the system's long-term behavior from the spectral characteristics (eigenvalues and eigenvectors) of its Koopman operator. For GRNs, the Koopman operator is based on the chemical master equation (CME), which provides a precise mathematical modeling framework for stochastic GRNs. Since the CME is typically analytically intractable, methods based on discretizing the CME operator have been developed. However, determining the number and location of metastable sets in the phase space as well as the transition rates between them remains computationally challenging, especially for large GRNs with many genes and interactions. A promising alternative method, called ISOKANN (invariant subspaces of Koopman operators with artificial neural networks) has been developed in the context of molecular dynamics. ISOKANN uses a combination of the power iteration and neural networks to learn the basis functions of an invariant subspace of the Koopman operator. In this paper, we extend the application of ISOKANN to the CME operator and apply it to two small GRNs: a genetic toggle switch model and a model for macrophage polarization. Our work opens a new field of application for the ISOKANN algorithm and demonstrates the potential of this algorithm for studying large GRNs.}, language = {en} }