Periodic Reporting for period 3 - BIOMAP (Biomarkers in Atopic Dermatitis and Psoriasis)
Período documentado: 2021-04-01 hasta 2022-03-31
The skin is an organ often affected by chronic inflammatory immune-mediated diseases, either as the primary target or through secondary manifestations. The two most common chronic inflammatory skin diseases are atopic dermatitis (AD) and psoriasis (Pso). Both are leading causes of non-fatal disease burden conferred by skin conditions, have marked negative impacts on quality of life, and confer a tremendous individual and societal burden. AD and Pso are associated with a strongly increased risk of comorbidities such as rhinitis and/or asthma in AD, psoriatic arthritis in Pso, and inflammatory bowel disease, rheumatoid arthritis, cardiometabolic traits and neuropsychiatric conditions in both. Despite much progress in the clinical and scientific understanding of AD and Pso, the precise mechanisms driving onset and course are poorly described, disease progression and/or development of comorbidities are unpredictable, and the optimal type and time-point for intervention is as yet unknown.
AD and Pso both show a remarkable degree of clinical heterogeneity the underpinnings of which are poorly understood. Thus, the delineation of disease subtypes and their mechanistic basis and molecular signatures, as well as biomarkers capable of assessing disease-related individual patient trajectories and response to therapies are key unmet needs. Ideally, current classifications would be replaced with an aetiology-based taxonomy that can be coupled with effective and safe treatment regimens for AD and Pso.
BIOMAP aims at fleshing out the molecular identity and subclasses of the underlying disease subtypes by integrating ‘omics’ data with detailed clinical, environmental and lifestyle information, and to identify candidate biomarkers for patient stratification. To this end, existing data from a wide variety of research studies and trials will be shared, augmented, analysed and followed-up.
The specific aims of BIOMAP are:
• To establish a pan-European BioResource for research into inflammatory skin diseases through alignment of clinical data with archived and newly obtained biological specimens.
• To establish a European clinical research network of clinicians, researchers and industry along with patient organisations and other major stakeholders to work in a co-ordinated way to refine clinical definitions and to define relevant and patient-centred outcomes, and to harmonise longitudinal recruitment, deep clinical evaluation and high-quality bio-sampling.
• To build a Data Warehouse assimilating existing and incoming clinical, experimental and omics data from high-quality patient collections, disease registries, epidemiological cohorts and trials with immediate access through a Data Analysis Portal.
• To identify disease subtypes and endotypes and associated signatures.
• To identify key host and environmental factors, and to generate predictive models and biomarkers of relevant disease outcomes.
AD and Pso both show a remarkable degree of clinical heterogeneity the underpinnings of which are poorly understood. Thus, the delineation of disease subtypes and their mechanistic basis and molecular signatures, as well as biomarkers capable of assessing disease-related individual patient trajectories and response to therapies are key unmet needs. Ideally, current classifications would be replaced with an aetiology-based taxonomy that can be coupled with effective and safe treatment regimens for AD and Pso.
BIOMAP aims at fleshing out the molecular identity and subclasses of the underlying disease subtypes by integrating ‘omics’ data with detailed clinical, environmental and lifestyle information, and to identify candidate biomarkers for patient stratification. To this end, existing data from a wide variety of research studies and trials will be shared, augmented, analysed and followed-up.
The specific aims of BIOMAP are:
• To establish a pan-European BioResource for research into inflammatory skin diseases through alignment of clinical data with archived and newly obtained biological specimens.
• To establish a European clinical research network of clinicians, researchers and industry along with patient organisations and other major stakeholders to work in a co-ordinated way to refine clinical definitions and to define relevant and patient-centred outcomes, and to harmonise longitudinal recruitment, deep clinical evaluation and high-quality bio-sampling.
• To build a Data Warehouse assimilating existing and incoming clinical, experimental and omics data from high-quality patient collections, disease registries, epidemiological cohorts and trials with immediate access through a Data Analysis Portal.
• To identify disease subtypes and endotypes and associated signatures.
• To identify key host and environmental factors, and to generate predictive models and biomarkers of relevant disease outcomes.
• A European Clinical Research Network (CRN) comprising more than 150 clinicians, scientists, and representatives of patient organisations across Europe has been established. Relevant roles (including Clinical Research, Bioinformatics/Statistics, Data/Sample Management, Software/Systems Development, Clinical Staff, Project Management, Pharmaceutical R&D), and individuals’ contributions and respective areas of expertise, have been catalogued in a comprehensive contact database – BIOMAP CRN – to enable rapid cross-consortium communication.
• A pan-European bioresource is available to BIOMAP researchers with high-quality biosamples being collected at multiple European sites. The technical platform for managing access to and transport of samples (the Virtual Biobank) has been finalised.
• The technical infrastructure for data collection, integration and analysis has been established and populated (the BIOMAP Data and Analysis Portal). A robust and secure data management plan along with detailed guidelines and a governance framework 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) are in place. Novel tools and methods to enable fast, efficient investigation of data have been made available to all BIOMAP partners through a user-friendly interface.
Publicly available data: doi: 10.5281/zenodo.4009497; doi: 10.5281/zenodo.4740406; GEO acc. nr. GSE157194;
• For the first time, a “Glossary” enabling harmonization and improving the comparability of existing studies with different methodologies, research objectives and outcomes by converting similar variables to a common format was created by a specialist team that has scoped out the current knowledge-base and expert opinion on biomarkers, disease diagnosis, clinical characteristics and outcome, and initiated formal, in-depth reviews of the literature where necessary. The network has also reviewed the clinical characteristics of BIOMAP cohorts, prioritising and categorising those of importance, and also established the methodological pipeline to establish the glossary of terms. The BIOMAP Glossary for harmonisation of clinical data has been published open access (doi: 10.5281/zenodo.4746584) and is continuously being used to harmonize BIOMAP datasets and to support collaborative research outside BIOMAP.
• First molecular signatures and mechanisms associated with AD and Pso and potential endotypes thereof as well as candidate biomarkers were identified and have been published.
• Large-scale population-based analyses identified key host and environment factors modulating the skin microbiome; a first research paper has been published (doi: 10.1111/bjd.20072) and a second one is under review.
• Classification of AD and Pso disease subtypes using data on microbial populations present on the skin (the „cutaneotypes”) is underway.
• Novel techniques for identifying and analysing skin and blood cells at a single-cell level have been developed and deployed in patient samples for both AD and Pso patients.
• A pan-European bioresource is available to BIOMAP researchers with high-quality biosamples being collected at multiple European sites. The technical platform for managing access to and transport of samples (the Virtual Biobank) has been finalised.
• The technical infrastructure for data collection, integration and analysis has been established and populated (the BIOMAP Data and Analysis Portal). A robust and secure data management plan along with detailed guidelines and a governance framework 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) are in place. Novel tools and methods to enable fast, efficient investigation of data have been made available to all BIOMAP partners through a user-friendly interface.
Publicly available data: doi: 10.5281/zenodo.4009497; doi: 10.5281/zenodo.4740406; GEO acc. nr. GSE157194;
• For the first time, a “Glossary” enabling harmonization and improving the comparability of existing studies with different methodologies, research objectives and outcomes by converting similar variables to a common format was created by a specialist team that has scoped out the current knowledge-base and expert opinion on biomarkers, disease diagnosis, clinical characteristics and outcome, and initiated formal, in-depth reviews of the literature where necessary. The network has also reviewed the clinical characteristics of BIOMAP cohorts, prioritising and categorising those of importance, and also established the methodological pipeline to establish the glossary of terms. The BIOMAP Glossary for harmonisation of clinical data has been published open access (doi: 10.5281/zenodo.4746584) and is continuously being used to harmonize BIOMAP datasets and to support collaborative research outside BIOMAP.
• First molecular signatures and mechanisms associated with AD and Pso and potential endotypes thereof as well as candidate biomarkers were identified and have been published.
• Large-scale population-based analyses identified key host and environment factors modulating the skin microbiome; a first research paper has been published (doi: 10.1111/bjd.20072) and a second one is under review.
• Classification of AD and Pso disease subtypes using data on microbial populations present on the skin (the „cutaneotypes”) is underway.
• Novel techniques for identifying and analysing skin and blood cells at a single-cell level have been developed and deployed in patient samples for both AD and Pso patients.
The scale of the BIOMAP consortium is unprecedented in the field of skin diseases. In a large-scale and well-coordinated manner, BIOMAP partners bring together biological samples, clinical information and ‘omics’ data from existing patient collections along with outstanding clinical and research expertise from diverse and complementary fields. Using this collaborative approach accompanied with data harmonization and standardized analysis strategies, BIOMAP pursues to answer open questions in the field using state-of-the-art methods in epidemiology, molecular profiling, skin biology and mathematical modelling to define new disease subpopulations (endotypes) and associated biomarkers. We expect findings to drive rapid drug discovery to target causal mechanisms. Biomarkers used alongside clinical signs will enable clinicians to know who, when and how to intervene, matching strategy (prevention, modification of risk factors, drug therapy) to particularly subgroups of AD and Pso (endotypes) to shift our current reactive, imprecise practice to pro-active strategies that encompass disease biology and life-time trajectory, with major benefit to people with AD and Pso. BIOMAP is a major endeavour on the way to precision medicine in inflammatory skin disease.