Periodic Reporting for period 1 - EXIMIOUS (Mapping Exposure-Induced Immune Effects: Connecting the Exposome and the Immunome)
Berichtszeitraum: 2020-01-01 bis 2021-06-30
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 combining innovative ways of 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 (see figure 1). Novel bio-informatics tools will be developed that will first combine and then analyse 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 be able 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 combining innovative ways of 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 (see figure 1). Novel bio-informatics tools will be developed that will first combine and then analyse 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 be able 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’ (see figure 2). Novel bioinformatics tools, based on systems immunology and machine learning, will be used to integrate and analyse the huge datasets and to construct ‘immune fingerprints’ that reflect a person’s lifetime exposome and identify ‘immune fingerprints’ that are early signs of poor health and predictors of disease at the individual level.
In the first project period (M1-M18), the EXIMIOUS partners have developed and validated novel methods, prepared protocols for sampling campaigns and aligned strategies between the various cohorts, including general and birth cohorts, disease cohorts and occupational cohorts. Several meetings and discussions took place to organize and align our study. Ethics requirements were continuously considered and monitored. Pilot studies are ongoing (e.g. in vitro studies) or are being prepared (e.g. protocol plan and pilot study in Romanian cohorts). We have laid down important groundwork for the complex task ahead.
Simultaneously to the scientific preparation of the project – which mainly involved WP2 (Population studies), WP3 (Exposomics), WP4 (Immunomics) and WP5 (Multi-omics) – we invested strongly in WP1 (Management and coordination), WP7 (Dissemination and Communication) and WP8-WP10 (Ethics requirements). An overview of our Work Plan and Work Packages is presented in figure 3. The coordinating team at KU Leuven meets on a weekly basis to follow-up closely on the management of coordination of the project. We have monthly meetings with the Project Steering Committee to coordinate our project. Our Scientific Advisory Board – consisting of five experts in different fields of expertise – advises us with regard to the scientific coordination of the EXIMIOUS project alongside the General Assembly meetings, which take place twice a year. An important preparatory task that took place in the first project period was the development of our Data Management Plan (DMP), submitted in M6 and updated in M18. Good data management is of great importance to a large project like EXIMIOUS, with huge datasets that will be brought together. The EXIMIOUS website (https://www.eximious-h2020.eu/) contains information about our project, outcomes and outreach material, which 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 conference, EHEN network day and EXIMIOUS symposium.
In the first project period (M1-M18), the EXIMIOUS partners have developed and validated novel methods, prepared protocols for sampling campaigns and aligned strategies between the various cohorts, including general and birth cohorts, disease cohorts and occupational cohorts. Several meetings and discussions took place to organize and align our study. Ethics requirements were continuously considered and monitored. Pilot studies are ongoing (e.g. in vitro studies) or are being prepared (e.g. protocol plan and pilot study in Romanian cohorts). We have laid down important groundwork for the complex task ahead.
Simultaneously to the scientific preparation of the project – which mainly involved WP2 (Population studies), WP3 (Exposomics), WP4 (Immunomics) and WP5 (Multi-omics) – we invested strongly in WP1 (Management and coordination), WP7 (Dissemination and Communication) and WP8-WP10 (Ethics requirements). An overview of our Work Plan and Work Packages is presented in figure 3. The coordinating team at KU Leuven meets on a weekly basis to follow-up closely on the management of coordination of the project. We have monthly meetings with the Project Steering Committee to coordinate our project. Our Scientific Advisory Board – consisting of five experts in different fields of expertise – advises us with regard to the scientific coordination of the EXIMIOUS project alongside the General Assembly meetings, which take place twice a year. An important preparatory task that took place in the first project period was the development of our Data Management Plan (DMP), submitted in M6 and updated in M18. Good data management is of great importance to a large project like EXIMIOUS, with huge datasets that will be brought together. The EXIMIOUS website (https://www.eximious-h2020.eu/) contains information about our project, outcomes and outreach material, which 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 conference, EHEN network day and EXIMIOUS symposium.
The innovation potential of EXIMIOUS lies in the fact that, with this consortium, we have brought together and—very importantly—linked the expertise from fields that simply did not interact before. By linking the expertise, we will make a major leap forward in mapping the exposome, as we will broaden its scope to include the immunome. By assessing the immunome, we are able 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. We will also contribute to the development of these commercial tools for patients, consumers, employees and employers. 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 analyse 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 that 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. We will also contribute to the development of these commercial tools for patients, consumers, employees and employers. 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 analyse 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 that 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.