Table 1.
Participating institutions in the EarlyCause project.
Table 2.
Table of hypotheses for longitudinal human data, animal and cellular models.
Fig 1.
Schematic overview of the EarlyCause project, that will study the link between ELS (1) and multi-morbidity (3), as mediated by biological pathways (2).
Large-scale life course human data (4), as well as experimental and computational models, will be used to identify and validate the causative mechanisms.
Fig 2.
Overall methodology of the EarlyCause project, including (A) research platform of harmonised data from existing resources, research protocols and best practices; (B) triangulation approach, which will capitalise on the complementary strengths of epidemiological and genetic methods in humans, experimental animal and cellular models, and in silico data integration pipelines; and (C) expected results such as new biomarkers and clinical knowledge.
Fig 3.
Differences between (1) simple multivariate analysis and (2) latent modelling of psycho-cardio-metabolic multi-morbidity implemented in EarlyCause.
Fig 4.
Overview of the experiments and analyses in rodents to identify molecular pathways linking ELS to PCM multi-morbidity.
Fig 5.
Overview of the cellular modelling experiences.
SCFAs (Short-chain fatty acids).
Table 3.
Biochemical and cellular candidate pathways that will be investigated in vitro.
Fig 6.
Overview of the EarlyCause centralised research platform, which will allow us to upload, search and manage human and experimental data for investigating ELS-induced multi-morbidity.
Fig 7.
Overview of the research directions affected by EarlyCause.