Abnormalities in intron retention characterize patients with systemic lupus erythematosus

Xiaoqian Sun, Computer Science Department, George Washington University, Washington, DC, 20052, USA.
Zhichao Liu, Physics Department, George Washington University, Washington, DC, 20052, USA.
Zongzhu Li, Physics Department, George Washington University, Washington, DC, 20052, USA.
Zhouhao Zeng, Physics Department, George Washington University, Washington, DC, 20052, USA.
Weiqun Peng, Physics Department, George Washington University, Washington, DC, 20052, USA.
Jun Zhu, Mokobio Biotechnology R&D Center, 1445 Research Blvd, Suite 150, Rockville, MD, 20850, USA.
Joel Zhao, Walt Whitman High School, Bethesda, MD, 20817, USA.
Chenghao Zhu, Mclean High School, McLean, VA, 22101, USA.
Chen Zeng, Physics Department, George Washington University, Washington, DC, 20052, USA. chenz@gwu.edu.
Nathaniel Stearrett, Computational Biology Institute, Milken Institute School of Public Health, George Washington University, Washington, DC, 20052, USA.
Keith A. Crandall, Computational Biology Institute, Milken Institute School of Public Health, George Washington University, Washington, DC, 20052, USA. kcrandall@gwu.edu.
Prathyusha Bachali, RILITE Research Institute and AMPEL BioSolutions, 250 W Main St, Ste 300, Charlottesville, VA, 22902, USA.
Amrie C. Grammer, RILITE Research Institute and AMPEL BioSolutions, 250 W Main St, Ste 300, Charlottesville, VA, 22902, USA.
Peter E. Lipsky, RILITE Research Institute and AMPEL BioSolutions, 250 W Main St, Ste 300, Charlottesville, VA, 22902, USA. peterlipsky@comcast.net.

Document Type

Journal Article

Publication Date

3-29-2023

Journal

Scientific reports

Volume

13

Issue

1

DOI

10.1038/s41598-023-31890-4

Abstract

Regulation of intron retention (IR), a form of alternative splicing, is a newly recognized checkpoint in gene expression. Since there are numerous abnormalities in gene expression in the prototypic autoimmune disease systemic lupus erythematosus (SLE), we sought to determine whether IR was intact in patients with this disease. We, therefore, studied global gene expression and IR patterns of lymphocytes in SLE patients. We analyzed RNA-seq data from peripheral blood T cell samples from 14 patients suffering from systemic lupus erythematosus (SLE) and 4 healthy controls and a second, independent data set of RNA-seq data from B cells from16 SLE patients and 4 healthy controls. We identified intron retention levels from 26,372 well annotated genes as well as differential gene expression and tested for differences between cases and controls using unbiased hierarchical clustering and principal component analysis. We followed with gene-disease enrichment analysis and gene-ontology enrichment analysis. Finally, we then tested for significant differences in intron retention between cases and controls both globally and with respect to specific genes. Overall decreased IR was found in T cells from one cohort and B cells from another cohort of patients with SLE and was associated with increased expression of numerous genes, including those encoding spliceosome components. Different introns within the same gene displayed both up- and down-regulated retention profiles indicating a complex regulatory mechanism. These results indicate that decreased IR in immune cells is characteristic of patients with active SLE and may contribute to the abnormal expression of specific genes in this autoimmune disease.

Department

Biostatistics and Bioinformatics

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