Periodic Reporting for period 3 - EXIMIOUS (Mapping Exposure-Induced Immune Effects: Connecting the Exposome and the Immunome)
Berichtszeitraum: 2023-01-01 bis 2024-06-30
Immune-mediated, non-communicable diseases, such as autoimmune diseases, allergic diseases and asthma, are chronic disorders in which the interaction between exposome and immune system plays a pivotal role. As prevalence and societal costs of these diseases are rising in the EU, a holistic approach is needed.
The overall objective of EXIMIOUS is to bring about a new way of assessing the human exposome by characterizing and quantifying multiple environmental exposures (exposomics) and mapping exposure-induced immune effects (immunomics). In several cohorts—covering the entire lifespan, including prenatal life—we will extensively map the exposome, the immunome (immune system), other omics (for example genomics) and clinical and socio-economic data. Novel bio-informatics tools will be developed that will first combine and then analyze these large datasets. By doing so, we aim to better understand the factors that lead to exposure-related immune effects at different stages of people’s lives and pinpoint the most critical forms of exposure and the groups of people most at risk in order to put in place the right preventative actions and policies at the individual, group and population levels.
We will build a multifaceted toolbox for researchers, policy makers, clinicians and the general public containing the exposome/immunome tools developed during the project to help assess the impact of the exposome on the immune system at the level of individuals and populations. This will allow policy makers to grasp the components of the exposome that needs to be prioritized, to design targeted preventive policies, to reduce healthcare and socioeconomic costs, leading to greater wellbeing for the EU population.
The overall objective of EXIMIOUS is to bring about a new way of assessing the human exposome by characterizing and quantifying multiple environmental exposures (exposomics) and mapping exposure-induced immune effects (immunomics). In several cohorts—covering the entire lifespan, including prenatal life—we will extensively map the exposome, the immunome (immune system), other omics (for example genomics) and clinical and socio-economic data. Novel bio-informatics tools will be developed that will first combine and then analyze these large datasets. By doing so, we aim to better understand the factors that lead to exposure-related immune effects at different stages of people’s lives and pinpoint the most critical forms of exposure and the groups of people most at risk in order to put in place the right preventative actions and policies at the individual, group and population levels.
We will build a multifaceted toolbox for researchers, policy makers, clinicians and the general public containing the exposome/immunome tools developed during the project to help assess the impact of the exposome on the immune system at the level of individuals and populations. This will allow policy makers to grasp the components of the exposome that needs to be prioritized, to design targeted preventive policies, to reduce healthcare and socioeconomic costs, leading to greater wellbeing for the EU population.
The EXIMIOUS consortium – consisting of 15 partners in 7 countries – gathers high-level experts in immunology, toxicology, clinical medicine, environmental hygiene, epidemiology, bio-informatics and sensor development. We use two main methodologies—one starting from the exposome, the other starting from disease—that ‘meet in the middle’. Novel bioinformatics tools, based on systems immunology and machine learning, will be used to integrate and analyze the datasets and to construct ‘immune fingerprints’ that reflect a person’s lifetime exposome and/or reveal early signs of poor health, predicting disease at the individual level.
In the second reporting period, the primary focus of the EXIMIOUS partners has been the sample and data collection in the various cohorts (WP2 (Population Studies), WP3 (Exposure)). Partners invested strongly in the development and validation of protocols for sample collection. Additional efforts have been put towards the development of novel methods and assessment strategies, which are now being applied to the sample collection. An important aspect of this was the alignment of strategies between the different cohorts (general population, disease cohort, occupational cohort). The exposure assessment strategies are described in deliverable D3.1: exposure dataset. Likewise, for the collection of biological samples, updated version of the sample collection protocol (deliverable D4.1: SOP) have been made available through the open KU Leuven Research Data Repository (doi: 10.1097/EE9.0000000000000193). Ethics requirements were continuously considered and monitored (WP8-10 (Ethics Requirements)).
In WP4 (Immunomics), WP5 (Multi-omics) and WP6 (Statistics and Systems Immunology), important groundwork was laid down for the complex analyses task ahead. In vitro studies are being performed towards better understanding of the internal exposome in WP4-5. In WP6, the first results applying Artificial Intelligence on the DOC*X cohort were made available in deliverable D6.1: Output of neural network analyses.
Simultaneously to the scientific preparation of the project, we invested strongly in WP1 (Management and coordination) and WP7 (Dissemination and Communication). An overview of our Work Plan and Work Packages is presented in figure 3. The coordinating team at KU Leuven holds weekly management meetings, organizes the monthly Project Steering Committee and consults with the Scientific Advisory Board at least twice a year, alongside our EXIMIOUS General Assemblies. A Data Management Plan (DMP), has been submitted in M6 and updated in M18 and M36; good data management is of great importance to a large project like EXIMIOUS, and EXIMIOUS is also preparing a detailed DMP checklist to be shared as part of the EIXMIOUS toolbox. The EXIMIOUS website (https://www.eximious-h2020.eu/(öffnet in neuem Fenster)) contains information about our project, outcomes and outreach material, and is continuously updated. Several project activities took place within the EXIMIOUS consortium (e.g. Kick-off meeting, General Assembly meetings), as well as beyond our project, such as the EHEN events and EXIMIOUS symposium series (https://www.eximious-h2020.eu/outreach/videos/(öffnet in neuem Fenster)).
In the second reporting period, the primary focus of the EXIMIOUS partners has been the sample and data collection in the various cohorts (WP2 (Population Studies), WP3 (Exposure)). Partners invested strongly in the development and validation of protocols for sample collection. Additional efforts have been put towards the development of novel methods and assessment strategies, which are now being applied to the sample collection. An important aspect of this was the alignment of strategies between the different cohorts (general population, disease cohort, occupational cohort). The exposure assessment strategies are described in deliverable D3.1: exposure dataset. Likewise, for the collection of biological samples, updated version of the sample collection protocol (deliverable D4.1: SOP) have been made available through the open KU Leuven Research Data Repository (doi: 10.1097/EE9.0000000000000193). Ethics requirements were continuously considered and monitored (WP8-10 (Ethics Requirements)).
In WP4 (Immunomics), WP5 (Multi-omics) and WP6 (Statistics and Systems Immunology), important groundwork was laid down for the complex analyses task ahead. In vitro studies are being performed towards better understanding of the internal exposome in WP4-5. In WP6, the first results applying Artificial Intelligence on the DOC*X cohort were made available in deliverable D6.1: Output of neural network analyses.
Simultaneously to the scientific preparation of the project, we invested strongly in WP1 (Management and coordination) and WP7 (Dissemination and Communication). An overview of our Work Plan and Work Packages is presented in figure 3. The coordinating team at KU Leuven holds weekly management meetings, organizes the monthly Project Steering Committee and consults with the Scientific Advisory Board at least twice a year, alongside our EXIMIOUS General Assemblies. A Data Management Plan (DMP), has been submitted in M6 and updated in M18 and M36; good data management is of great importance to a large project like EXIMIOUS, and EXIMIOUS is also preparing a detailed DMP checklist to be shared as part of the EIXMIOUS toolbox. The EXIMIOUS website (https://www.eximious-h2020.eu/(öffnet in neuem Fenster)) contains information about our project, outcomes and outreach material, and is continuously updated. Several project activities took place within the EXIMIOUS consortium (e.g. Kick-off meeting, General Assembly meetings), as well as beyond our project, such as the EHEN events and EXIMIOUS symposium series (https://www.eximious-h2020.eu/outreach/videos/(öffnet in neuem Fenster)).
The innovation potential of EXIMIOUS lies in the fact that, with this consortium, we have brought together and linked the expertise from fields that did not interact before. The collective expertise will make a major leap forward in mapping the exposome, by including the immunome, to grasp the relevant components of the exposome, i.e. the components that need to be prioritized. Therefore, this approach offers an important tool for policy makers to design targeted preventive actions—instead of prevention, which is too broad and dispersed to have an impact.
Innovation potential in mapping the exposome. For assessing the exposome, the main innovative potential of EXIMIOUS is in combining measurements (multiple exposures, multiple exposure route) and sensor development combined with novel bioinformatics tools. Until now, the determination of complex exposures in homes or workplaces has been time-consuming and requires elaborated logistics and analytical techniques. We will overcome this problem with user-friendly, compact, low-cost tools and devices to assess the exposome at the individual level. The lead users who will benefit from these tools are researchers, environmental and occupational health practitioners, clinicians and pathologists, as it will simplify the assessment of the exposome. Imec's HSI sensors and cameras have, for example, been demonstrated at TRL7 (system prototype demonstration in operational environment) for several other applications.
Immunomics. Another main innovation potential of EXIMIOUS will be the discovery of immune fingerprints by combining novel ways to assess an individual’s immune system (WP4-WP5) with the systems immunology approach (WP6), which has seen major advances in the past decade regarding the ability to combine and analyze large datasets coming from new immuno-phenotyping platforms. Validated immune fingerprints would benefit researchers and policy makers, because they would serve as an additional tool to assess the internal exposome, and so complement other exposure-assessment tools. Also, businesses can benefit because they will become more aware of the threats their workers are potentially exposed to. Immune fingerprints that can predict disease would benefit clinicians and patients, as it would enable them to intervene and stop hazardous exposures and prevent immune-related disease. This will benefit the individual, but also have a major impact at the societal level, by reducing healthcare and socioeconomic costs.
Innovation potential in mapping the exposome. For assessing the exposome, the main innovative potential of EXIMIOUS is in combining measurements (multiple exposures, multiple exposure route) and sensor development combined with novel bioinformatics tools. Until now, the determination of complex exposures in homes or workplaces has been time-consuming and requires elaborated logistics and analytical techniques. We will overcome this problem with user-friendly, compact, low-cost tools and devices to assess the exposome at the individual level. The lead users who will benefit from these tools are researchers, environmental and occupational health practitioners, clinicians and pathologists, as it will simplify the assessment of the exposome. Imec's HSI sensors and cameras have, for example, been demonstrated at TRL7 (system prototype demonstration in operational environment) for several other applications.
Immunomics. Another main innovation potential of EXIMIOUS will be the discovery of immune fingerprints by combining novel ways to assess an individual’s immune system (WP4-WP5) with the systems immunology approach (WP6), which has seen major advances in the past decade regarding the ability to combine and analyze large datasets coming from new immuno-phenotyping platforms. Validated immune fingerprints would benefit researchers and policy makers, because they would serve as an additional tool to assess the internal exposome, and so complement other exposure-assessment tools. Also, businesses can benefit because they will become more aware of the threats their workers are potentially exposed to. Immune fingerprints that can predict disease would benefit clinicians and patients, as it would enable them to intervene and stop hazardous exposures and prevent immune-related disease. This will benefit the individual, but also have a major impact at the societal level, by reducing healthcare and socioeconomic costs.