Morpheus - Establishing the first sustainable software infrastructure for multi-scale modelling and simulation of multicellular biological systems

• Applicant: Dr. Lutz Brusch
• Subject Area: Bioinformatics and Theoretical Biology ; Developmental Biology
• Term: from 2018 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 391070520

Throughout the life sciences, computational modelling is an increasingly important tool to study the dynamical behavior of biological tissues and organs. A fast-growing community of researchers in systems bio-medicine is seeking solutions for multi-scale simulations of multicellular systems to link the emergent spatio-temporal dynamics at the histological level to known molecular and genetic regulatory networks in order to aid drug discovery.To address these needs, we developed the software prototype Morpheus under the auspices of the Virtual Liver Network. Morpheus is (1) able to simulate multi-scale models, (2) features an integrated modelling environment with a user-friendly graphical user interface, (3) provides plugin interfaces to ensure extensibility. Crucially, it provides the world-wide first and only solution to encode multicellular simulation models in a declarative language, called MorpheusML. This enables the clear separation of modelling from programming. Morpheus has been released open source under BSD license on the GitLab code repository.Three hurdles prevent a larger audience from fully capitalising on Morpheus, (1) the lack of sustainable provision, (2) lack of an infrastructure for simulation reproducibility and model exchange, and (3) lack of an infrastructure for community development of the Morpheus/MorpheusML framework.This project has three corresponding objectives: (1) Quality assurance and Dissemination of Morpheus including unit-tests, continuous integration/delivery, documentation and training; (2) Establishment of a collaborative infrastructure for storage and exchange of multicellular models based on MorpheusML and a citable model repository; (3) The development of long-term strategies and infrastructure for interoperability of multicellular simulation software and the orchestration of the ongoing standardisation process. Therewith, we will establish the first sustainable software infrastructure for multi-scale modeling and simulation of multicellular biological systems through application-oriented research, development and implementation of e-Research technologies. This approach will be evaluated by user interactions and world experts supporting the project. The infrastructure will be stably hosted at the Center for Information Services and High Performance Computing of TU Dresden. Lack of reproducibility of simulation studies due to missing standards also afflicts other research fields, which would in the long term benefit from this infrastructure demonstrator.As a mid-term (six years) result, computational modeling of multicellular systems will become accessible to a wide community of scientists in biomedical research and their models will become reproducible and sharable through the citable model repository, expediting the scientific progress in understanding tissue development and complex diseases.Keywords: Systems biology, Systems medicine, Standardisation for multicellular systems, Model repository

• DFG Programme: Research data and software (Scientific Library Services and Information Systems)