Integrative network fusion-based multi-omics study for biomarker identification and patient classification of rheumatoid arthritis

Zihe Ding; Wenjia Chen; Hao Wu; Weijie Li; Xia Mao; Weiwei Su; Yanqiong Zhang; Na Lin

doi:10.1186/s13020-023-00750-8

Integrative network fusion-based multi-omics study for biomarker identification and patient classification of rheumatoid arthritis

Chin Med. 2023 May 4;18(1):48. doi: 10.1186/s13020-023-00750-8.

Authors

Zihe Ding¹, Wenjia Chen¹, Hao Wu², Weijie Li¹, Xia Mao¹, Weiwei Su², Yanqiong Zhang³, Na Lin⁴

Affiliations

¹ Research Center of Traditional Chinese Medicine Theory and Literatures, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing, 100700, China.
² School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
³ Research Center of Traditional Chinese Medicine Theory and Literatures, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing, 100700, China. yqzhang@icmm.ac.cn.
⁴ Research Center of Traditional Chinese Medicine Theory and Literatures, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing, 100700, China. nlin@icmm.ac.cn.

Abstract

Background: Cold-dampness Syndrome (RA-Cold) and Hot-dampness Syndrome (RA-Hot) are two distinct groups of rheumatoid arthritis (RA) patients with different clinical symptoms based on traditional Chinese medicine (TCM) theories and clinical empirical knowledge. However, the biological basis of the two syndromes has not been fully elucidated, which may restrict the development of personalized medicine and drug discovery for RA diagnosis and therapy.

Methods: An integrative strategy combining clinical transcriptomics, phenomics, and metabolomics data based on clinical cohorts and adjuvant-induced arthritis rat models was performed to identify novel candidate biomarkers and to investigate the biological basis of RA-Cold and RA-Hot.

Results: The main clinical symptoms of RA-Cold patients are joint swelling, pain, and contracture, which may be associated with the dysregulation of T cell-mediated immunity, osteoblast differentiation, and subsequent disorders of steroid biosynthesis and phenylalanine metabolism. In contrast, the main clinical symptoms of RA-Hot patients are fever, irritability, and vertigo, which may be associated with various signals regulating angiogenesis, adrenocorticotropic hormone release, and NLRP3 inflammasome activation, leading to disorders of steroid biosynthesis, nicotinamide, and sphingolipid metabolism. IL17F, 5-HT, and IL4I1 were identified as candidate biomarkers of RA-Cold, while S1P and GLNS were identified as candidate biomarkers of RA-Hot.

Conclusions: The current study presents the most comprehensive metabonomic and transcriptomic profiling of serum, urine, synovial fluid, and synovial tissue samples obtained from RA-Cold and RA-Hot patients and experimental animal models to date. Through the integration of multi-omics data and clinical independent validation, a list of novel candidate biomarkers of RA-Cold and RA-Hot syndromes were identified, that may be useful in improving RA diagnosis and therapy.

Keywords: Biomarker identification; Integration of the multi-omics data; Patient classification; Precision medicine; Rheumatoid arthritis.

Abstract

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