title: B-Cell and Monocyte Contribution to Systemic Lupus Erythematosus Identified by Cell-Type-Specific Differential Expression Analysis in RNA-Seq Data.
abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by complex interplay among immune cell types. SLE activity is experimentally assessed by several blood tests, including gene expression profiling of heterogeneous populations of cells in peripheral blood. To better understand the contribution of different cell types in SLE pathogenesis, we applied the two methods in cell-type-specific differential expression analysis, csSAM and DSection, to identify cell-type-specific gene expression differences in heterogeneous gene expression measures obtained using RNA-seq technology. We identified B-cell-, monocyte-, and neutrophil-specific gene expression differences. Immunoglobulin-coding gene expression was altered in B-cells, while a ribosomal signature was prominent in monocytes. On the contrary, genes differentially expressed in the heterogeneous mixture of cells did not show any functional enrichment. Our results identify antigen binding and structural constituents of ribosomes as functions altered by B-cell- and monocyte-specific gene expression differences, respectively. Finally, these results position both csSAM and DSection methods as viable techniques for cell-type-specific differential expression analysis, which may help uncover pathogenic, cell-type-specific processes in SLE.
authors.affiliation: Department of Biostatistics, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Mikhail G
authors.initials: MG
authors.lastname: Dozmorov
authors.affiliation: Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dominguez
authors.affiliation: Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
authors.forename: Krista
authors.initials: K
authors.lastname: Bean
authors.affiliation: Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Macwana
authors.affiliation: Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
authors.forename: Virginia
authors.initials: V
authors.lastname: Roberts
authors.affiliation: Department of Biostatistics, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Edmund
authors.initials: E
authors.lastname: Glass
authors.affiliation: Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
authors.forename: Judith A
authors.initials: JA
authors.lastname: James
authors.affiliation: Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
authors.forename: Joel M
authors.initials: JM
authors.lastname: Guthridge
keywords: DSection; RNA-seq; SLE; cell-type-specific; csSAM; deconvolution