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

在整个生命科学中，计算模型是研究生物组织和器官动态行为的一个日益重要的工具。一个快速增长的系统生物医学研究社区正在为多细胞系统的多尺度模拟寻找解决方案，以将组织水平上的紧急时空动力学与已知的分子和基因调控网络联系起来，以帮助药物发现。为了满足这些需求，我们在虚拟肝脏网络的支持下开发了软件原型Morpheus。Morpheus(1)能够模拟多尺度模型，(2)具有用户友好的图形用户界面的集成建模环境，(3)提供插件接口以确保可扩展性。至关重要的是，它提供了世界上第一个也是唯一一个以声明性语言MorpheusML编码多细胞模拟模型的解决方案。这使得建模与编程能够明显分离。Morpheus已经在GitLab代码库的BSD许可下发布了开放源码。三个障碍阻碍了更多的受众充分利用Morpheus，(1)缺乏可持续的供应，(2)缺乏用于模拟重现性和模型交换的基础设施，(3)缺乏用于社区开发的基础设施Morpheus/MorpheusML框架。本项目有三个相应的目标：(1)Morpheus的质量保证和传播，包括单元测试，持续的集成/交付，文档和培训；(2)建立一个基于MorpheusML的多细胞模型存储和交换的协作基础设施和一个可聚集的模型库；(3)为多细胞模拟软件的互操作性制定长期战略和基础设施，并协调正在进行的标准化进程。在此基础上，我们将通过面向应用的研究、开发和实施e-Research技术，建立第一个可持续的多细胞生物系统多尺度建模和模拟的软件基础设施。这一方法将由支持该项目的用户互动和世界专家进行评估。基础设施将稳定地托管在德累斯顿理工大学信息服务和高性能计算中心。由于缺乏标准，模拟研究缺乏重复性，这也困扰着其他研究领域，从长远来看，这些领域将从这个基础设施示范中受益。作为中期(6年)的结果，生物医学研究中的广泛科学家将可以使用多细胞系统的计算建模，他们的模型将通过可引用的模型库变得可重现和共享，从而加速了解组织发育和复杂疾病的科学进步。关键词：系统生物学，系统医学，多细胞系统的标准化，模型库

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