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In this white paper, we describe the founding of a new ELIXIR Community - the Systems Biology Community - and its proposed future contributions to both ELIXIR and the broader community of systems biologists in Europe and worldwide. The Community believes that the infrastructure aspects of systems biology - databases, (modelling) tools and standards development, as well as training and access to cloud infrastructure - are not only appropriate components of the ELIXIR infrastructure, but will prove key components of ELIXIR’s future support of advanced biological applications and personalised medicine.By way of a series of meetings, the Community identified seven key areas for its future activities, reflecting both future needs and previous and current activities within ELIXIR Platforms and Communities. These are: overcoming barriers to the wider uptake of systems biology; linking new and existing data to systems biology models; interoperability of systems biology resources; further development and embedding of systems medicine; provisioning of modelling as a service; building and coordinating capacity building and training resources; and supporting industrial embedding of systems biology.A set of objectives for the Community has been identified under four main headline areas: Standardisation and Interoperability, Technology, Capacity Building and Training, and Industrial Embedding. These are grouped into short-term (3-year), mid-term (6-year) and long-term (10-year) objectives.

This deliverable reports on the outcome of Task 9.1 ”Analysis of the training needs of different EOSC-Life users”. An online survey was developed to get structured feedback on the training landscape from the Biological and Medical ESFRI research infrastructures (BMS RIs). One of the aims was to identify gaps in existing training offers and developing a plan on how to address these gaps. 35 responses were received, from 13 research infrastructures (RIs). All 13 RIs provide training as part of their activities, which is a great starting point for the EOSC-Life training strategy. The training needs with respect to EOSC-Life topics were analysed, which RI(s) expressed interest in the training topic, which RI(s) already provide training and which RI(s) are interested in providing training in the future. The survey results underline that the 12 pre-selected topics in the grant proposal cover the EOSC-Life training needs extremely well. However, the survey also highlighted that there is a need for outreach and awareness raising about EOSC in general, and EOSC-Life specifically, to RI staff within and outside of the project. In addition training needs were collected from the other EOSC-Life WPs and discussed during the project retreat in October. As a next step, we will facilitate that training in high demand areas will be expanded, e.g. by facilitating exchange of experience between RIs that expressed interest in providing training in a given topic with those already providing this training. In addition, as response to a high demand of introductory training on EOSC-Life and the clear need for EOSC-related outreach, a Translator group was initiated.

In the current thesis the model of the ROS management network is built using the domino principle. The model offers insight into the design principles underlying the ROS management network and enlightens its functionality in the diseases such as cancer and Parkinson’s disease (PD). It is validated using experimental data. The model is used for in silico study of the ROS management dynamics under the stress conditions (oxidative stress). This highlights the phenomena of both adaptation to stress and the stress accumulation effect in case of repeated stress. This study also helps to discover the potential ways to a personalized treatment of the insufficient ROS management. The different ways of a control of the ROS management network are shown using the optimal control approach. Obtained results could be used for a seeking of the treatment strategies to fix the ROS management failures caused by an oxidative stress, neurodegenerative diseases, etc. Or, in vice versa, to develop the ways of a controllable cell death that might be used in cancer research.

Background: Levodopa-induced dyskinesia (LID) is a common adverse effect of levodopa, one of the main therapeutics used to treat the motor symptoms of Parkinson's disease (PD). Previous evidence suggests a connection between LID and a disruption of the dopaminergic system as well as genes implicated in PD, including GBA1 and LRRK2 ., Objectives: To investigate the effects of genetic variants on risk and time to LID., Methods: We performed a genome-wide association study (GWAS) and analyses focused on GBA1 and LRRK2 variants. We also calculated polygenic risk scores including risk variants for PD and variants in genes involved in the dopaminergic transmission pathway. To test the influence of genetics on LID risk we used logistic regression, and to examine its impact on time to LID we performed Cox regression including 1,612 PD patients with and 3,175 without LID., Results: We found that GBA1 variants were associated with LID risk (OR=1.65, 95% CI=1.21-2.26, p=0.0017) and LRRK2 variants with reduced time to LID onset (HR=1.42, 95% CI=1.09-1.84, p=0.0098). The fourth quartile of the PD PRS was associated with increased LID risk (OR fourth_quartile =1.27, 95% CI=1.03-1.56, p =0.0210). The third and fourth dopamine pathway PRS quartiles were associated with a reduced time to development of LID (HR third_quartile =1.38, 95% CI=1.07-1.79, p =0.0128; HR fourth_quartile =1.38, 95% CI=1.06-1.78, p =0.0147)., Conclusions: This study suggests that variants implicated in PD and in the dopaminergic transmission pathway play a role in the risk/time to develop LID. Further studies will be necessary to examine how these findings can inform clinical care., Competing Interests: ZGO has received consulting fees from Lysosomal Therapeutics Inc., Idorsia, Prevail Therapeutics, Denali, Ono Therapeutics, Neuron23, Handl Therapeutics, UBC, Bial Biotech Inc., Bial, Deerfield, Guidepoint, Lighthouse and VanquaBio. None of these companies were involved in any parts of preparing, drafting and publishing this study. ZKW is partially supported by the NIH/NIA and NIH/NINDS (1U19AG063911, FAIN: U19AG063911), Mayo Clinic Center for Regenerative Medicine, the gifts from the Donald G. and Jodi P. Heeringa Family, the Haworth Family Professorship in Neurodegenerative Diseases fund, and The Albertson Parkinson's Research Foundation. He serves as PI or Co-PI on Biohaven Pharmaceuticals, Inc. (BHV4157-206) and Vigil Neuroscience, Inc. (VGL101-01.002, VGL101-01.201, PET tracer development protocol, Cfthsf1r biomarker and repository project, and ultra-high field MRI in the diagnosis and management of CSF1R-related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia) projects/grants. He serves as Co-PI of the Mayo Clinic APDA Center for Advanced Research and as an external advisory board member for the Vigil Neuroscience, Inc., and as a consultant on neurodegenerative medical research for Eli Lilli & Company.