During this period, progress has continued towards accomplishing the project's objectives as highlighted below.
The TO_AITION cloud platform has been implemented and maintained, enabling data storage and processing of the many datasets of the project. Harmonization activities rendering data in a similar format so that they can be analyzed together have also taken place. There has been enrichment of the Athero-Express Biobank with OLINK® proteomics, providing new data for circulating biomarkers, and the Young Finns Study with methylation epigenomics and metagenomics data.
For the analysis of the various cohorts, numerous methodologies are employed, and new analytical and computational models, and pipelines, have been developed. The construction of multiplex disease networks, the identification of shared risk markers common to both CVD outcomes and depression, and the uncovering of synergistic associations within disease networks and markers linked to multimorbidity has progressed. Analyses have been performed using datasets from the NESDA, HELIUS, LIFELINES, LURIC and YFS studies. Work to implement a range of causal inference methods deployed in the networks generated has continued. These include Mendelian randomization coupled with machine learning.
The development of purpose-built human cell-based and animal models for the evaluation of causality of novel factors and pathways identified is close to completion. Standardized whole blood and PBMC culture stimulation assays for assessing immune responsiveness have been developed, and adapted for implementation on a robotic platform enabling high-throughput processing. These assays are now applied to stored samples from relevant cohorts. The generation of new genetically modified mice needed has continued and mice are currently being analyzed.
For the Identification of new biomarkers, a novel and computationally efficient methodology has been developed and is used to explore data from the LURIC cohort and UK Biobank.
The first versions of the LOC device and the risk stratification platform integrating a plethora of models for the diagnosis and prediction of CVD and depression have been produced.
Regulatory and ethical aspects of the project, including Ethics approval forms, monotoring by an Ethics Advisory Board, access rights, compliance with the GDPR etc, have also been effectively dealt with during this period. Various dissemination, exploitation and awareness activities have been implemented and include a project website, videos and interviews of TO_AITION researchers, an electronic newsletter, social media accounts, printed material, awareness-raising activities from the European Society of Cardiology, and others.
Finally, an efficient management structure dealing with contractual, financial and legal administration, and day-to-day management is employed.
