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• W2944955712 abstract "ABSTRACT Objective Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease that is difficult to treat. There is currently no optimal stratification of patients with SLE, and thus responses to available treatments are unpredictable. Here, we developed a new stratification scheme for patients with SLE, based on the whole-blood transcriptomes of patients with SLE. Methods We applied machine learning approaches to RNA-sequencing (RNA-seq) datasets to stratify patients with SLE into four distinct clusters based on their gene expression profiles. A meta-analysis on two recently published whole-blood RNA-seq datasets was carried out and an additional similar dataset of 30 patients with SLE and 29 healthy donors was contributed in this research; 141 patients with SLE and 51 healthy donors were analysed in total. Results Examination of SLE clusters, as opposed to unstratified SLE patients, revealed underappreciated differences in the pattern of expression of disease-related genes relative to clinical presentation. Moreover, gene signatures correlated to flare activity were successfully identified. Conclusion Given that disease heterogeneity has confounded research studies and clinical trials, our approach addresses current unmet medical needs and provides a greater understanding of SLE heterogeneity in humans. Stratification of patients based on gene expression signatures may be a valuable strategy to harness disease heterogeneity and identify patient populations that may be at an increased risk of disease symptoms. Further, this approach can be used to understand the variability in responsiveness to therapeutics, thereby improving the design of clinical trials and advancing personalised therapy." @default.
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• W2944955712 date "2019-05-24" @default.
• W2944955712 modified "2023-10-13" @default.
• W2944955712 title "Machine learning applied to whole-blood RNA-sequencing data uncovers distinct subsets of patients with systemic lupus erythematosus" @default.
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• W2944955712 doi "https://doi.org/10.1101/647719" @default.
• W2944955712 hasPublicationYear "2019" @default.
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