Ethnicity-specific transcriptomic variation in immune cells and correlation with disease activity in systemic lupus erythematosus

Andreoletti, G.; Lanata, C. M.; Paranjpe, I.; Jain, T. S.; Nititham, J.; Taylor, K. E.; Combes, A. J.; Maliskova, L.; Jimmie Ye, C.; Katz, P.; Dall Era, M.; Yazdany, J.; Criswell, L. A.; Sirota, M.

doi:10.1101/2020.10.30.362715

bioRxiv · 10.1101/2020.10.30.362715

Ethnicity-specific transcriptomic variation in immune cells and correlation with disease activity in systemic lupus erythematosus

Andreoletti, G.·Lanata, C. M.·Paranjpe, I.·Jain, T. S.·Nititham, J.·Taylor, K. E.·Combes, A. J.·Maliskova, L.·Jimmie Ye, C.·Katz, P.·Dall Era, M.·Yazdany, J.·Criswell, L. A.·Sirota, M.

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Abstract

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease in which outcomes vary among different racial groups. The aim of this study is to leverage large-scale transcriptomic data from diverse populations to better sub-classify SLE patients into more clinically actionable groups. We leverage cell sorted RNA-seq data (CD14+ monocytes, B cells, CD4+T cells, and NK cells) from 120 SLE patients (63 Asian and 57 White individuals) and apply a four tier analytical approach to identify SLE subgroups within this multiethnic cohort: unsupervised clustering, differential expression analyses, gene co-expression analyses, and machine learning. K-means clustering on the individual cell type data resulted in three clusters for CD4 and CD14, and two clusters for B cells and NK cells. Correlation analysis revealed significant positive associations between the transcriptomic clusters of each immune cell and clinical parameters including disease activity and ethnicity. We then explored differentially expressed genes between Asian and White groups for each cell-type. The shared differentially expressed genes across the four cell types were involved in SLE or other autoimmune related pathways. Co-expression analysis identified similarly regulated genes across samples and grouped these genes into modules. Samples were grouped into White-high, Asians-high (high disease activity defined by SLEDAI score >=6) and White-low, Asians-low (SLEDAI < 6). Random forest classification of disease activity in the White and Asian cohorts showed the best classification in CD4+ T cells in White. The results from these analyses will help stratify patients based on their gene expression signatures to enable precision medicine for SLE.

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Andreoletti, G., Lanata, C. M., Paranjpe, I., Jain, T. S., Nititham, J., Taylor, K. E., Combes, A. J., Maliskova, L., Jimmie Ye, C., Katz, P., Dall Era, M., Yazdany, J., Criswell, L. A., Sirota, M.. 2020-11-01. Ethnicity-specific transcriptomic variation in immune cells and correlation with disease activity in systemic lupus erythematosus. https://doi.org/10.1101/2020.10.30.362715

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