A comprehensive single-cell atlas of freshly-dissociated human synovium in inflammatory arthritis with an optimized dissociation protocol for prospective fresh synovial biopsy collection

Edalat, Sam G.; Gerber, Reto; Houtman, Miranda; Kuret, Tadeja; Izanc, Nadja; Micheroli, Raphael; Buerki, K.; Burja, Blaž; Pauli, Chantal; Rotar, Žiga; Tomšič, Matija; Čučnik, Saša; Distler, Oliver; Ospelt, Caroline; Sodin-Semrl, Snežna; Robinson, Mark D.; Frank-Bertoncelj, Mojca

doi:10.21203/rs.3.rs-1702574/v1

Cited by 2 publications

(1 citation statement)

References 32 publications

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“…Regarding cells participating in the pathogenesis of synovitis, altered endothelial cell (EC) function and angiogenesis have been proven to play an important role. Edalat et al 12 created a comprehensive single-cell atlas of synovial ECs in patients with inflammatory arthritis, which provides a reference data set for future EC subtype-specific functional studies. As for inflammatory cells, by applying single-cell RNA sequencing together with B and T cell repertoire sequencing in synovial tissue and matched peripheral blood, Meednu et al 13 revealed tissue-specific clonal expansion and in situ selection of B and T cells in the synovium of RA patients.…”

Section: Single-cell Sequencing Revealed the Underlying Pathogenesis ...mentioning

confidence: 99%

New insights into the pathogenesis and management of rheumatoid arthritis

Jin

Zeng

et al. 2022

Chronic Diseases and Translational Medicine

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Over the past few decades, understanding of the pathogenesis of rheumatoid arthritis (RA) has improved substantially. Insights into the cellular and molecular mechanisms involved in RA have enabled the discovery of new therapeutic targets and led to the development of biologics and targeted synthetic disease‐modifying antirheumatic drugs. In parallel with the improvement in therapies, the evolution of strategies in the management of RA has also contributed considerably to better outcomes in patients. Major changes include the development of disease activity measures, formulation of the treat‐to‐target principles as well as increased attention to comorbidities. The presence of comorbidities such as cardiovascular diseases may increase the mortality of RA patients, affect their treatment strategies and result in worse outcomes. Therefore, prevention and management of certain high‐risk comorbidities have become increasingly important in the long‐term treatment of RA. In this study, we summarized new insights into the pathogenesis and management of rheumatoid arthritis and associated comorbidities, with a special focus on the 2021 update of the American College of Rheumatology (ACR) guideline for RA and key reports presented at the 2021 ACR convergence.

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Section: Single-cell Sequencing Revealed the Underlying Pathogenesis ...mentioning

confidence: 99%

New insights into the pathogenesis and management of rheumatoid arthritis

Jin

Zeng

et al. 2022

Chronic Diseases and Translational Medicine

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Contextual AI models for single-cell protein biology

Huang

Sumathipala

et al. 2023

Preprint

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Understanding protein function and discovering molecular therapies require deciphering the cell types in which proteins act as well as the interactions between proteins. However, modeling protein interactions across diverse biological contexts, such as tissues and cell types, remains a significant challenge for existing algorithms. We introduce PINNACLE, a flexible geometric deep learning approach that is trained on contextualized protein interaction networks to generate context-aware protein representations. Leveraging a human multi-organ single-cell transcriptomic atlas, PINNACLE provides 394,760 protein representations split across 156 cell type contexts from 24 tissues and organs. PINNACLE's contextualized representations of proteins reflect cellular and tissue organization and PINNACLE's tissue representations enable zero-shot retrieval of the tissue hierarchy. Pretrained PINNACLE protein representations can be adapted for downstream tasks: to enhance 3D structure-based protein representations (PD-1/PD-L1 and B7-1/CTLA-4) at cellular resolution and to study the genomic effects of drugs across cellular contexts. PINNACLE outperforms state-of-the-art, yet context-free, models in nominating therapeutic targets for rheumatoid arthritis and inflammatory bowel diseases, and can pinpoint cell type contexts that are more predictive of therapeutic targets than context-free models (29 out of 156 cell types in rheumatoid arthritis; 13 out of 152 cell types in inflammatory bowel diseases). PINNACLE is a network-based contextual AI model that dynamically adjusts its outputs based on biological contexts in which it operates.

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A comprehensive single-cell atlas of freshly-dissociated human synovium in inflammatory arthritis with an optimized dissociation protocol for prospective fresh synovial biopsy collection

Cited by 2 publications

References 32 publications

New insights into the pathogenesis and management of rheumatoid arthritis

New insights into the pathogenesis and management of rheumatoid arthritis

Contextual AI models for single-cell protein biology

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