Abstract
Original language | English |
---|---|
Article number | 1002629 |
Journal | Frontiers in immunology |
Volume | 13 |
DOIs | |
Publication status | Published - 9 Nov 2022 |
Keywords
- LIPUS
- atopic dermatitis
- dOFM
- immunomediated diseases
- liquid biopsy
- omic analyses
- ulcerative colitis
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In: Frontiers in immunology, Vol. 13, 1002629, 09.11.2022.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - ImmUniverse Consortium
T2 - Multi-omics integrative approach in personalized medicine for immune-mediated inflammatory diseases
AU - Vetrano, Stefania
AU - ImmUniverse Consortium
AU - Bouma, Gerben
AU - Benschop, Robert J.
AU - Birngruber, Thomas
AU - Costanzo, Antonio
AU - D’Haens, G. R. A. M.
AU - Frasca, Loredana
AU - Hillenbrand, Rainer
AU - Iversen, Lars
AU - Johansen, Claus
AU - Kaser, Arthur
AU - Koenen, Hans J. P. M.
AU - Noehammer, Christa
AU - Peyrin-Biroulet, Laurent
AU - Raes, Jeroen
AU - Ricotti, Leonardo
AU - Rosenstiel, Philip
AU - Satagopam, Venkata P.
AU - Schreiber, Stefan
AU - Vermeire, Severine
AU - Wollenberg, Andreas
AU - Weidinger, Stephan
AU - Ziemek, Daniel
AU - Danese, Silvio
N1 - Funding Information: This ImmUniverse ( www.immuniverse.eu ) has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No. 853995. The JU receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA. The content provided in this publication reflects only the author’s view and neither the IMI JU nor the European Commission are responsible for any use that may be made of the information it contains. Funding Information: ImmUniverse is a large collaborative consortium that received funding from the Innovative Medicines Initiative (IMI), which is sponsored by the European Union (Horizon 2020), and in-kind contributions from participating pharmaceutical companies within the European Federation of Pharmaceutical Industries and Associations (EFPIA). ImmUniverse is a partnership between academic experts in UC and AD, technical expert providers, patient organizations and large pharmaceutical companies (Annex 1), aiming to advance our understanding of the molecular and cellular mechanisms underlying both UC and AD by implementing a multi-omics approach in both blood and disease tissue. The novelty of this research project is to combine state-of-the-art omics profiling and informatics expertise to identify signatures of tissue-derived and circulating biomarkers and elucidate mechanistic principles that are informative for disease severity and future disease progression of these 2 different IMIDs. To this end, the study will follow a registry-like design, with physician choice of targeted therapies and will recruit >500 UC and AD adult patients (male and female patients ≥ 18 years of age) with complete data including a clinical follow up over at least 12 months. Multi-omics data from different molecular profiling of tissue microenvironment and accessible matrices, such as blood and stool, using multiple technologies (single cell sequencing, multi-omics approaches) will be integrated with clinical data. Signatures identified in blood or other matrices will be correlated with signatures in the tissue. The ultimate goal is therefore two-fold: (A) Integration of different omics layers on single tissue data to derive predictive and prognostic multi-omics signatures and (B) identification of signatures correlating between tissue and blood. Multi-omics predictive models will undergo thorough crossvalidation to derive robust estimates for classification performance, which will be benchmarked against comparable single-omics performances and scrutinized by ImmUniverse’s clinical team for their clinical utility. Reported will be not only the performance estimates, but also the predictive features (signatures) including a measure of their respective importance for classification. Tissue-derived signatures will be correlated with data derived from accessible matrices (blood and stool), using variations of canonical correlation analysis capable of dealing with the dimensionality of the data. Again, such circulating features shall be reported for the subsequent task of enriching the detected features with data from open sources. Tissue-specific molecular interaction networks and pathway maps will be identified and visualized for both diseases and compared for the tissue-specific determination of shared and disease-specific processes and pathways. Hormonal and genetic factors contribute significantly to sex differences in immune function and disease pathogenesis. Along these lines ImmUniverse will systematically take into account biological sex differences as well as cultural/behavioral influences from phenotype/outcome definitions to tissue-based molecular analyses through to data models. Therefore, we will consider the potential confounding influence of gender at all stages of analysis and incorporate gender as a co-variate. Based on these features and enriched with data from the literature, a disease map will be developed in close collaboration with clinical partners and domain experts, which will describe the mechanisms of the pathophysiology behind the investigated diseases, highlighting their overlapping and specific areas in the context of specific tissues. This approach will not only generate translatable signatures for disease prognosis and therapy response prediction in UC and AD, but it will also develop a first mechanistic hypothesis of the underlaying pathophysiologies (both shared and disease-specific). This integrated analysis approach is depicted in . Aggregated results will be shared with public via scientific publications and patients/patient organizations. Patients have right to request their data and we will securely share the corresponding data with requested study participant. Researchers will be able to search the aggregated metadata indexed in the data catalogue and submit a request to Data Access Committee (DAC) to access necessary datasets. Once the DAC approves the request, the requested data will be securely shared with the researcher. Publisher Copyright: Copyright © 2022 Vetrano, Bouma, Benschop, Birngruber, Costanzo, D’Haens, Frasca, Hillenbrand, Iversen, Johansen, Kaser, Koenen, Noehammer, Peyrin-Biroulet, Raes, Ricotti, Rosenstiel, Satagopam, Schreiber, Vermeire, Wollenberg, Weidinger, Ziemek, Danese and ImmUniverse Consortium.
PY - 2022/11/9
Y1 - 2022/11/9
N2 - Immune mediated inflammatory diseases (IMIDs) are a heterogeneous group of debilitating, multifactorial and unrelated conditions featured by a dysregulated immune response leading to destructive chronic inflammation. The immune dysregulation can affect various organ systems: gut (e.g., inflammatory bowel disease), joints (e.g., rheumatoid arthritis), skin (e.g., psoriasis, atopic dermatitis), resulting in significant morbidity, reduced quality of life, increased risk for comorbidities, and premature death. As there are no reliable disease progression and therapy response biomarkers currently available, it is very hard to predict how the disease will develop and which treatments will be effective in a given patient. In addition, a considerable proportion of patients do not respond sufficiently to the treatment. ImmUniverse is a large collaborative consortium of 27 partners funded by the Innovative Medicine Initiative (IMI), which is sponsored by the European Union (Horizon 2020) and in-kind contributions of participating pharmaceutical companies within the European Federation of Pharmaceutical Industries and Associations (EFPIA). ImmUniverse aims to advance our understanding of the molecular mechanisms underlying two immune-mediated diseases, ulcerative colitis (UC) and atopic dermatitis (AD), by pursuing an integrative multi-omics approach. As a consequence of the heterogeneity among IMIDs patients, a comprehensive, evidence-based identification of novel biomarkers is necessary to enable appropriate patient stratification that would account for the inter-individual differences in disease severity, drug efficacy, side effects or prognosis. This would guide clinicians in the management of patients and represent a major step towards personalized medicine. ImmUniverse will combine the existing and novel advanced technologies, including multi-omics, to characterize both the tissue microenvironment and blood. This comprehensive, systems biology-oriented approach will allow for identification and validation of tissue and circulating biomarker signatures as well as mechanistic principles, which will provide information about disease severity and future disease progression. This truly makes the ImmUniverse Consortium an unparalleled approach.
AB - Immune mediated inflammatory diseases (IMIDs) are a heterogeneous group of debilitating, multifactorial and unrelated conditions featured by a dysregulated immune response leading to destructive chronic inflammation. The immune dysregulation can affect various organ systems: gut (e.g., inflammatory bowel disease), joints (e.g., rheumatoid arthritis), skin (e.g., psoriasis, atopic dermatitis), resulting in significant morbidity, reduced quality of life, increased risk for comorbidities, and premature death. As there are no reliable disease progression and therapy response biomarkers currently available, it is very hard to predict how the disease will develop and which treatments will be effective in a given patient. In addition, a considerable proportion of patients do not respond sufficiently to the treatment. ImmUniverse is a large collaborative consortium of 27 partners funded by the Innovative Medicine Initiative (IMI), which is sponsored by the European Union (Horizon 2020) and in-kind contributions of participating pharmaceutical companies within the European Federation of Pharmaceutical Industries and Associations (EFPIA). ImmUniverse aims to advance our understanding of the molecular mechanisms underlying two immune-mediated diseases, ulcerative colitis (UC) and atopic dermatitis (AD), by pursuing an integrative multi-omics approach. As a consequence of the heterogeneity among IMIDs patients, a comprehensive, evidence-based identification of novel biomarkers is necessary to enable appropriate patient stratification that would account for the inter-individual differences in disease severity, drug efficacy, side effects or prognosis. This would guide clinicians in the management of patients and represent a major step towards personalized medicine. ImmUniverse will combine the existing and novel advanced technologies, including multi-omics, to characterize both the tissue microenvironment and blood. This comprehensive, systems biology-oriented approach will allow for identification and validation of tissue and circulating biomarker signatures as well as mechanistic principles, which will provide information about disease severity and future disease progression. This truly makes the ImmUniverse Consortium an unparalleled approach.
KW - LIPUS
KW - atopic dermatitis
KW - dOFM
KW - immunomediated diseases
KW - liquid biopsy
KW - omic analyses
KW - ulcerative colitis
UR - http://www.scopus.com/inward/record.url?scp=85142780817&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fimmu.2022.1002629
DO - https://doi.org/10.3389/fimmu.2022.1002629
M3 - Article
C2 - 36439150
SN - 1664-3224
VL - 13
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 1002629
ER -