Protein profiling and network enrichment analysis in individuals before and after the onset of rheumatoid arthritis
Abstract Background Antibodies and upregulated cytokines and chemokines predate the onset of rheumatoid arthritis (RA) symptoms. We aimed to identify the pathways related to the early processes leading to RA development, as well as potential novel biomarkers, using multiple protein analyses. Methods...
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ftdatacite:10.6084/m9.figshare.c.4784316 2023-05-15T17:44:56+02:00 Protein profiling and network enrichment analysis in individuals before and after the onset of rheumatoid arthritis Brink, Mikael Lundquist, Anders Alexeyenko, Andrey Lejon, Kristina Rantapää-Dahlqvist, Solbritt 2019 https://dx.doi.org/10.6084/m9.figshare.c.4784316 https://springernature.figshare.com/collections/Protein_profiling_and_network_enrichment_analysis_in_individuals_before_and_after_the_onset_of_rheumatoid_arthritis/4784316 unknown figshare https://dx.doi.org/10.1186/s13075-019-2066-9 CC BY 4.0 https://creativecommons.org/licenses/by/4.0 CC-BY Biochemistry Cell Biology Genetics FOS Biological sciences Ecology Immunology FOS Clinical medicine Developmental Biology Hematology Collection article 2019 ftdatacite https://doi.org/10.6084/m9.figshare.c.4784316 https://doi.org/10.1186/s13075-019-2066-9 2021-11-05T12:55:41Z Abstract Background Antibodies and upregulated cytokines and chemokines predate the onset of rheumatoid arthritis (RA) symptoms. We aimed to identify the pathways related to the early processes leading to RA development, as well as potential novel biomarkers, using multiple protein analyses. Methods A case-control study was conducted within the Biobank of northern Sweden. The plasma samples from 118 pre-symptomatic individuals (207 samples; median predating time 4.1 years), 79 early RA patients, and 74 matched controls were analyzed. The levels of 122 unique proteins with an acknowledged relationship to autoimmunity were analyzed using 153 antibodies and a bead-based multiplex system (FlexMap3D; Luminex Corp.). The data were analyzed using multifactorial linear regression model, random forest, and network enrichment analysis (NEA) based on the 10 most significantly differentially expressed proteins for each two-by-two group comparison, using the MSigDB collection of hallmarks. Results There was a high agreement between the different statistical methods to identify the most significant proteins. The adipogenesis and interferon alpha response hallmarks differentiated pre-symptomatic individuals from controls. These two hallmarks included proteins involved in innate immunity. Between pre-symptomatic individuals and RA patients, three hallmarks were identified as follows: apical junction, epithelial mesenchymal transition, and TGF-β signaling, including proteins suggestive of cell interaction, remodulation, and fibrosis. The adipogenesis and heme metabolism hallmarks differentiated RA patients from controls. Conclusions We confirm the importance of interferon alpha signaling and lipids in the early phases of RA development. Network enrichment analysis provides a tool for a deeper understanding of molecules involved at different phases of the disease progression. Article in Journal/Newspaper Northern Sweden DataCite Metadata Store (German National Library of Science and Technology) |
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DataCite Metadata Store (German National Library of Science and Technology) |
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topic |
Biochemistry Cell Biology Genetics FOS Biological sciences Ecology Immunology FOS Clinical medicine Developmental Biology Hematology |
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Biochemistry Cell Biology Genetics FOS Biological sciences Ecology Immunology FOS Clinical medicine Developmental Biology Hematology Brink, Mikael Lundquist, Anders Alexeyenko, Andrey Lejon, Kristina Rantapää-Dahlqvist, Solbritt Protein profiling and network enrichment analysis in individuals before and after the onset of rheumatoid arthritis |
topic_facet |
Biochemistry Cell Biology Genetics FOS Biological sciences Ecology Immunology FOS Clinical medicine Developmental Biology Hematology |
description |
Abstract Background Antibodies and upregulated cytokines and chemokines predate the onset of rheumatoid arthritis (RA) symptoms. We aimed to identify the pathways related to the early processes leading to RA development, as well as potential novel biomarkers, using multiple protein analyses. Methods A case-control study was conducted within the Biobank of northern Sweden. The plasma samples from 118 pre-symptomatic individuals (207 samples; median predating time 4.1 years), 79 early RA patients, and 74 matched controls were analyzed. The levels of 122 unique proteins with an acknowledged relationship to autoimmunity were analyzed using 153 antibodies and a bead-based multiplex system (FlexMap3D; Luminex Corp.). The data were analyzed using multifactorial linear regression model, random forest, and network enrichment analysis (NEA) based on the 10 most significantly differentially expressed proteins for each two-by-two group comparison, using the MSigDB collection of hallmarks. Results There was a high agreement between the different statistical methods to identify the most significant proteins. The adipogenesis and interferon alpha response hallmarks differentiated pre-symptomatic individuals from controls. These two hallmarks included proteins involved in innate immunity. Between pre-symptomatic individuals and RA patients, three hallmarks were identified as follows: apical junction, epithelial mesenchymal transition, and TGF-β signaling, including proteins suggestive of cell interaction, remodulation, and fibrosis. The adipogenesis and heme metabolism hallmarks differentiated RA patients from controls. Conclusions We confirm the importance of interferon alpha signaling and lipids in the early phases of RA development. Network enrichment analysis provides a tool for a deeper understanding of molecules involved at different phases of the disease progression. |
format |
Article in Journal/Newspaper |
author |
Brink, Mikael Lundquist, Anders Alexeyenko, Andrey Lejon, Kristina Rantapää-Dahlqvist, Solbritt |
author_facet |
Brink, Mikael Lundquist, Anders Alexeyenko, Andrey Lejon, Kristina Rantapää-Dahlqvist, Solbritt |
author_sort |
Brink, Mikael |
title |
Protein profiling and network enrichment analysis in individuals before and after the onset of rheumatoid arthritis |
title_short |
Protein profiling and network enrichment analysis in individuals before and after the onset of rheumatoid arthritis |
title_full |
Protein profiling and network enrichment analysis in individuals before and after the onset of rheumatoid arthritis |
title_fullStr |
Protein profiling and network enrichment analysis in individuals before and after the onset of rheumatoid arthritis |
title_full_unstemmed |
Protein profiling and network enrichment analysis in individuals before and after the onset of rheumatoid arthritis |
title_sort |
protein profiling and network enrichment analysis in individuals before and after the onset of rheumatoid arthritis |
publisher |
figshare |
publishDate |
2019 |
url |
https://dx.doi.org/10.6084/m9.figshare.c.4784316 https://springernature.figshare.com/collections/Protein_profiling_and_network_enrichment_analysis_in_individuals_before_and_after_the_onset_of_rheumatoid_arthritis/4784316 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
https://dx.doi.org/10.1186/s13075-019-2066-9 |
op_rights |
CC BY 4.0 https://creativecommons.org/licenses/by/4.0 |
op_rightsnorm |
CC-BY |
op_doi |
https://doi.org/10.6084/m9.figshare.c.4784316 https://doi.org/10.1186/s13075-019-2066-9 |
_version_ |
1766147237819187200 |