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Biomarkers in Atopic Dermatitis and Psoriasis

Periodic Reporting for period 5 - BIOMAP (Biomarkers in Atopic Dermatitis and Psoriasis)

Reporting period: 2023-04-01 to 2024-03-31

Atopic dermatitis (AD) and psoriasis (Pso) are the two most common inflammatory diseases primarily affecting the skin and the leading cause of the non-fatal disease burden conferred by skin conditions. Despite much progress in the clinical and scientific understanding of AD and Pso, the precise mechanisms driving their manifestation and progression are not well understood, their trajectories and/or the development of comorbidities are unpredictable, and there are currently no markers available that could guide the selection, dosing and timing of intervention.
The overarching aims of BIOMAP are to resolve the enormous heterogeneity of these diseases and to address important medical needs by establishing a patient-focused understanding of AD and Pso, defining key mechanisms and pathways that operate in these diseases, re-classifying them based on their intrinsic biology (‘endotypes’), and identifying molecular signatures, which have the potential to be developed into biomarker assays. To this end BIOMAP assembles clinical and molecular data as well as high-quality biological samples from large-scale existing patient collections, disease registries, epidemiological studies and clinical trials, complements and integrates molecular data across multiple scales from pathways to cells and tissues, and links them to relevant and sufficiently detailed readouts.
More specifically, the main objectives are:
• To establish a collaborative network of clinicians, researchers and industry along with patient organisations and other major stakeholders, working in a co-ordinated way to refine clinical phenotypes and to define relevant and patient-centred outcomes.
• To form a European clinical research network for harmonized longitudinal recruitment, deep clinical phenotyping and high-quality bio-sampling to address gaps in the BioResource, and to optimise the clinical translational potential of BIOMAP.
• To establish a pan-European BioResource for research into inflammatory skin diseases through alignment of clinical data with archived and newly obtained molecular profiling data.
• To build a Data Warehouse assimilating existing and incoming clinical, experimental and multi-omics data from large high-quality patient collections, disease registries, epidemiological cohorts and industry trials with immediate access for analysis through Data Analysis Portal facilitating multi user interrogation to investigate interactions between clinical features and molecular pathways.
• To identify influential life events and environmental factors, and to generate predictive models and biomarkers of relevant disease outcomes (e.g. severity, progression, comorbidity development, therapy response) to guide patient management, and to direct therapy development and stratifiers for use in trials.
• To cross-reference findings from AD and Pso to look at similarities and differences that could be used to refine endotypes or inform selection of targets for therapy.
• To replace current classifications of AD and Pso with an aetiology-based taxonomy that can be coupled with effective and safe treatment regimens.
• A European Clinical Research Network (CRN) comprising clinicians, scientists, and patient representatives has been established and is actively participating in BIOMAP.
• A pan-European bioresource with a technical platform for managing access to and transport of samples (the Virtual Biobank) is available to BIOMAP researchers.
• A BIOMAP Data and Analysis Portal has been set up to integrate available data from patient collections, disease registries, epidemiological cohorts and industry trials as well as publicly available sources. A robust and secure data management plan along with detailed guidelines and a governance framework has been set in place for upload, storage and access along with legal documentation to enable data sharing between partners in full compliance with applicable regulatory guidelines including the General Data Protection Regulation (GDPR).
• A “Glossary” for harmonization of clinical data from diverse cohorts was established and published open access (doi: 10.5281/zenodo.4746584) and the vast majority of BIOMAP datasets has been harmonized based on the glossary. Likewise, a framework standardization for the definition of AD and PSO severity outcomes was set up (doi: 10.1093/bjd/ljae080). For (pre-) processing of molecular data resepctive consented pipelines were established.
• Multi-cohort analyses have identified important genetic mechanisms driving immune dysregulation in AD and PSO (doi: 10.1038/s41467-023-41180-2; doi: 10.1101/2023.10.04.23296543; doi: 10.1038/s41588-023-01545-1)
• Large-scale population- and registry-based analyses have identified key host and environment factors modulating the skin microbiome as well as the differential impact of established treatments (dois: 10.1111/all.15742; 10.1038/s41467-022-33906-5; 10.1016/j.jdermsci.2022.04.007; 10.1111/bjd.20072).
• Significant progress has been made in characterising clinical disease trajectories, and initial findings on childhood AD subtypes based on trajectory and severity of disease as well as clusters of multimorbidity in people with AD were published (dois: 10.1038/s41598-022-26357-x; 10.1111/bjd.19885).
• First AD and Pso candidate subphenotypes and endotypes along with associated molecular signatures were identified and published (dois: 10.1016/j.jaci.2022.02.001; 10.1016/j.jaci.2020.06.012; 10.1016/j.jid.2023.02.010).
• CRISPR/Cas9-based tools for generating in vitro model systems for multiomics analyes have been established and published (doi: 10.1016/j.jid.2023.02.021) and are accessible for BIOMAP partners.
• Genetic effect size estimates have successfully been used to validate UK biobank definitions of psoriasis (doi: 10.1016/j.jid.2023.02.010).
• Novel techniques for identifying and analysing skin and blood cells at a single-cell level have been developed and are currently deployed in patient samples for both AD and Pso patients (doi: 10.1038/s41467-024-44994-w; doi: 10.1016/j.jaci.2022.04.027).
The scale of the BIOMAP consortium is unprecedented in the field of skin diseases. In a large-scale and well-coordinated manner, BIOMAP partners have assembled clinical information, ‘omics’ data and biological samples from epidemiological and clinical studies along with outstanding clinical and research expertise from diverse and complementary fields. Using this collaborative approach accompanied with data harmonization, complementary molcular profiling and standardized advanced analysis strategies, BIOMAP performs integrated muli-omics analyses to identify subpopulations (subtypes and endotypes) of AD and PSO and associated molecular signatures and biomarkers. In parallel, tools for follow-up investigations and translation of results have been developed. First candidate disease subtypes defined on the transcriptomic, proteomic and/or microbial level are currently being verified and followed up using these tools to identify the respective dominant disease mechanisms and potential clinical implications. Results may support drug discovery to target causal mechanisms and support clinical decision-making so that the current reactive, imprecise practice can advance to more pro-active and stratified approaches. BIOMAP has enormous potential to advance patient care and to stimulate further research on precision medicine in inflammatory skin diseases.
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