Addressing the clinical unmet needs in primary Sjögren’s Syndrome through the sharing, harmonization and federated analysis of 21 European cohorts

Vasileios C Pezoulas,Roberta Priori,Chiara Baldini,Dorian Parisis,Manolis Tsiknakis,Christine Delporte,Saviana Gandolfo,Roberto Giacomelli,Thorsten May,Thomas Dörner,Iryna Lishchuk,Thymios Chondrogiannis,Roberto Gerli,Themis P Exarchos,Jan Burmeister,Wan-Fai Ng,Elena Bartoloni,Mariette Xavier,Dimitrios I Fotiadis,Salvatore De Vita,Hendrika Bootsma,Vassiliki Andronikou,Witte Torsten,Konstantinos Votis,Muhammad Shahnawaz Soyfoo,Athanasios G Tzioufas,Theodora Varvarigou,Aliki Venetsanopoulou,Κωνσταντίνα Κούρου ,Andreas V Goules ,Roland Johnsson ,Evangelia Zampeli ,Kathy L Sivils ,Nenad Filipović ,Michèle Bombardieri ,Joël A G Van Roon ,Loukas Chatzis ,Fotini N Skopouli ,Fanis G Kalatzis ,Jacques‐Olivier Pers ,Manuel Perez ,Valérie Devauchelle‐Pensec ,Manuel Ramos‐Casals ,Simon Bowman

doi:10.1016/j.csbj.2022.01.002

Abstract

For many decades, the clinical unmet needs of primary Sjögren’s Syndrome (pSS) have been left unresolved due to the rareness of the disease and the complexity of the underlying pathogenic mechanisms, including the pSS-associated lymphomagenesis process. Here, we present the HarmonicSS cloud-computing exemplar which offers beyond the state-of-the-art data analytics services to address the pSS clinical unmet needs, including the development of lymphoma classification models and the identification of biomarkers for lymphomagenesis. The users of the platform have been able to successfully interlink, curate, and harmonize 21 regional, national, and international European cohorts of 7,551 pSS patients with respect to the ethical and legal issues for data sharing. Federated AI algorithms were trained across the harmonized databases, with reduced execution time complexity, yielding robust lymphoma classification models with 85% accuracy, 81.25% sensitivity, 85.4% specificity along with 5 biomarkers for lymphoma development. To our knowledge, this is the first GDPR compliant platform that provides federated AI services to address the pSS clinical unmet needs.

Highlights

Primary Sjögren’s Syndrome is a chronic systemic autoimmune disease which is characterized by a wide spectrum of clinical manifestations varying from mild disease limited to exocrine glands to severe multi-systemic involvement [1,2,3]
The HarmonicSS cloud computing services delineated the clinical picture and unmet needs of Primary Sjögren’s Syndrome (pSS) through: (i) the utilization of a unique data governance framework that enables the extensive evaluation of the data protection agreement (DPA) and data protection impact assessment (DPIA) documents by the Data Controller’s
The existing platforms and tools that have been developed for data curation, harmonization and federated or distributed data analysis are presented in Supplementary Table 2 and compared against the core services of the HarmonicSS platform

Summary

Introduction

Primary Sjögren’s Syndrome (pSS) is a chronic systemic autoimmune disease which is characterized by a wide spectrum of clinical manifestations varying from mild disease limited to exocrine glands to severe multi-systemic involvement [1,2,3]. As in other systemic autoimmune or neoplastic diseases, the lack of patient stratification models in pSS: (i) increases the risk of producing unsatisfactory or suboptimal results in clinical trials employing novel and expensive drugs, and (ii) hampers the definition of evidence-based health policies. These two issues are related with the unmet needs in pSS which involve the development of robust lymphoma classification models and the extraction of biomarkers

Methods

Results

Conclusion