Brain Modelling as a Service: The Virtual Brain on EBRAINS Michael Schirnera,b,c,d,e, Lia Domidef, Dionysios Perdikisa,b, Paul Triebkorna,b,g, Leon Stefanovskia,b, Roopa Paia,b, Paula Prodanf, Bogdan Valeanf, Jessica Palmera,b, Chloê Langforda,b, André Blickensdörfera,b, Michiel van der Vlagh, Sandra Diaz-Pierh, Alexander Peyserh, Wouter Klijnh, Dirk Pleiteri,j, Anne Nahmi, Oliver Schmidk, Marmaduke Woodmang, Lyuba Zehll, Jan Fousekg, Spase Petkoskig, Lionel Kuschg, Meysam Hashemig, Daniele Marinazzom,n, Jean-François Mangino, Agnes Flöelp,q, Simisola Akintoyer, Bernd Carsten Stahls, Michael Cepict, Emily Johnsont, Gustavo Decou,v,w,x, Anthony R. McIntoshy, Claus C. Hilgetagz, a, Marc Morgank, Bernd Schulleri, Alex Uptonb, Colin McMurtrieb, Timo Dickscheidl, Jan G. Bjaaliec, Katrin Amuntsl,d, Jochen Mersmanne, Viktor Jirsag, Petra Rittera,b,c,d,e,* aBerlin Institute of Health at Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany bCharité – Universitätsmedizin Berlin, corporate memBer of Freie Universität Berlin and HumBoldt Universität zu Berlin, Department of Neurology with Experimental Neurology, Charitéplatz 1, 10117 Berlin, Germany cBernstein Focus State Dependencies of Learning & Bernstein Center for Computational Neuroscience, Berlin, Germany dEinstein Center for Neuroscience Berlin, Charitéplatz 1, 10117 Berlin, Germany eEinstein Center Digital Future, Wilhelmstraße 67, 10117 Berlin, Germany fCodemart, Str. Petofi Sandor, Cluj Napoca, Romania gInstitut de Neurosciences des Systèmes, Aix Marseille Université, Marseille, France hSimLaB Neuroscience, Jülich Supercomputing Centre (JSC), Institute for Advanced Simulation, JARA, Forschungszentrum Jülich GmBH, Jülich, Germany iJülich Supercomputer Centre, Forschungszentrum Jülich, Jülich, Germany jInstitut für Theoretische Physik, Universität RegensBurg, RegensBurg, Germany kSwiss Federal Institute of Technology Lausanne (EPFL), Campus Biotech, Geneva, Switzerland lInstitute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany mDepartment of Data-Analysis, Faculty of Psychology and Educational Sciences, Ghent University, Belgium nSan Camillo IRCSS, Venice, Italy oUniversité Paris-Saclay, CEA, CNRS, Neurospin, BaoBaB, Gif-sur-Yvette, France pDepartment of Neurology, University Medicine Greifswald, Greifswald, Germany qGerman Center for Neurodegenerative Diseases (DZNE) Standort Greifswald, Greifswald, Germany rLeicester De Montfort Law School, De Montfort University, Leicester, United Kingdom sCentre for Computing and Social ResponsiBility, De Montfort University, Leicester, United Kingdom tDepartment of Innovation and Digitalisation in Law, Faculty of Law, University of Vienna, Austria uCenter for Brain and Cognition, Computational Neuroscience Group, Department of Information and Communication Technologies, Universitat Pompeu Fabra, Barcelona, Spain vInstitució Catalana de la Recerca i Estudis Avançats, Barcelona, Spain wDepartment of Neuropsychology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany xSchool of Psychological Sciences, Turner Institute for Brain and Mental Health, Monash University, MelBourne, Clayton, Australia yBaycrest Health Sciences, Rotman Research Institute, Toronto, ON, Canada zInstitute of Computational Neuroscience, University Medical Center HamBurg-Eppendorf, Hamburg, Germany aDepartment of Health Sciences, Boston University, 635 Commonwealth Ave., Boston, Massachusetts 02215 bCSCS Swiss National Supercomputing Centre, Lugano, Switzerland cInstitute of Basic Medical Sciences, University of Oslo, Norway dC. and O. Vogt Institute for Brain Research, University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Germany eCodeBox GmBH, Stuttgart, Germany *Corresponding author: Petra Ritter, [email protected], Charitéplatz 1, 10117 Berlin, Germany 1 Keywords: brain modelling, cloud, connectome, neuroimaging, network model, high performance computing The Virtual Brain (TVB) is now available as open-source cloud ecosystem on EBRAINS, a shared digital research platform for brain science. It offers services for constructing, simulating and analysing brain network models (BNMs) including the TVB network simulator; magnetic resonance imaging (MRI) processing pipelines to extract structural and functional connectomes; multiscale co-simulation of spiking and large-scale networks; a domain specific language for automatic high-performance code generation from user- specified models; simulation-ready BNMs of patients and healthy volunteers; Bayesian inference of epilepsy spread; data and code for mouse brain simulation; and extensive educational material. TVB cloud services facilitate reproducible online collaboration and discovery of data assets, models, and software embedded in scalable and secure workflows, a precondition for research on large cohort data sets, better generalizability and clinical translation. Scientific studies are often difficult to (bit.ly/3ogLYtb). To provide replicate and findings often do not supercomputing resources, the HBP offers generalize in light of additional data (Aarts as part of the Interactive Computing E- et al., 2015; Ioannidis, 2005). The data and Infrastructure project access to compute the computational steps that produced the and storage resources of the Fenix findings as well as the explicit workflow infrastructure (fenix-ri.eu), a network of describing how to generate the results five European supercomputing centres. were identified as the minimal TVB services use EBRAINS core services for components for independent regeneration deployment (Figure 1). The 'Collaboratory' of computational results (Stodden et al., (Supplementary Note: The EBRAINS 2016). EBRAINS (European Brain Research Collaboratory) hosts light-weight INfrastructureS) is an open brain research workspaces, called 'collabs', where platform that makes data, tools and results research teams can exchange data and accessible to everyone within an work together on Office or Wiki environment that promotes reproducible documents, secured with access control. work. It offers cloud services for 'Lab' provides sandboxed JupyterLab collaborative online research, databases instances for developing applications and with annotated and curated data of many running code. Lab notebooks provide a modalities, atlases of human and rodent powerful interface to EBRAINS services, for brains, data processing workflows, data transfer as well as configuring and supercomputing resources, neuromorphic executing jobs on supercomputers. Data systems, and virtual robots. EBRAINS was can be found and accessed via the developed by the Human Brain Project 'KnowledgeGraph' (KG), which provides a (HBP), a research initiative funded by the graphical user interface (GUI) and European Commission with the mission to Application Programming Interface (API) decode the human brain (Amunts et al., for searching, inserting, editing, querying, 2019, 2016). TVB cloud services (Tables 1, aggregating, filtering and visual 2) were developed by the HBP subproject exploration of the data base. KG uses "The Virtual Brain" in collaboration with controlled vocabularies and ontologies, the two HBP partnering projects TVB-Cloud mapped with existing neuroimaging and (virtualbraincloud-2020.eu) and TVB-CD brain simulation ontologies 2 (Supplementary Note: Metadata rat brain atlas (Osen et al., 2019; Papp et annotations). Professional curation, al., 2014). The Multilevel Human Brain persistent DOIs, licensing, versioning, data Atlas uses the Julich-Brain probabilistic sharing agreements and protected cytoarchitectonic maps (Amunts et al., workflows enable secure, interoperable 2020) to link with template spaces such as and reusable sharing of data and services. BigBrain (Amunts et al., 2013) at the Containerized workflows and backend micrometer scale and MNI (Das et al., supercomputing resources enable 2016) at millimeter scale, and combines reproducible research that scales to the them with imaging-based maps of function demands of the project. A RESTful API is (Evans et al., 2012) and connectivity used for connecting different cloud (Guevara et al., 2017) to link a growing set components, authentication, data transfer of multimodal feature descriptions of the and supercomputer job scheduling. Atlas human brain, in order to capture brain Services provide common spatial reference organization in its different facets. spaces including a multilevel atlas of the human brain as well as the Waxholm Space Results The Virtual Brain End-to-end encryption drive.ebrains.eu Web GUI Graph database TVB Processing Pipeline wiki.ebrains.eu Sandboxing Container image openMINDS TVB-Multiscale metadata office.ebrains.eu iam.ebrains.eu REST-API Python notebooks Identity and access Fast_TVB management Visual graph Personal data lab.ebrains.eu explorer (Py)Unicore Python library TVB-HPC OpenShift Authentication Interfaces Metadata and querying Autorisation Bayesian virtual epileptic patient KnowledgeGraph Access control HPC HPC backend Data privacy Core services Deployment TVB services Figure 1. TVB on EBRAINS cloud ecosystem. Brain simulation and neuroimaging require personal data applicable to data protection regulation. Encryption, sandboxing and access control are used to protect personal data. EBRAINS provides core services: 'Drive' for hosting and sharing files; 'Wiki' and 'Office' to create workspaces and documents for collaborative research; 'Lab' for running live code in sandboxed JupyterLab instances; 'OpenShift' for orchestrating