Transcriptomic profile investigations highlight a putative role for NUDT16 in sepsis

Abstract

Sepsis is an aberrant systemic inflammatory response mediated by the acute activation of the innate immune system. Neutrophils are important contributors to the innate immune response that controls the infection, but harbour the risk of collateral tissue damage such as thrombosis and organ dysfunction. A better understanding of the modulations of cellular processes in neutrophils and other blood cells during sepsis is needed and can be initiated via transcriptomic profile investigations. To that point, the growing repertoire of publicly accessible transcriptomic datasets serves as a valuable resource for discovering and/or assessing the robustness of biomarkers. We employed systematic literature mining, reductionist approach to gene expression profile and empirical in vitro work to highlight the role of a Nudix hydrolase family member, NUDT16, in sepsis. The relevance and implication of the expression of NUDT16 under septic conditions and the putative functional roles of this enzyme are discussed.

Keywords: ADP-ribosylation; gene expression; mRNA decapping; nudix hydrolase; nudix hydrolase 16 (NUDT16); reductionist approach; sepsis.

FIGURE 1

NUDT16 gene and protein expression in septic conditions and extraction of biological concepts associated with NUDT16 from the literature. (A) Expression levels of the Nudix Hydrolase family member 16 gene (NUDT16) after in vitro exposure of neutrophils to control or septic serum (data from GSE49755). (B) NUDT16 gene expression (expression values, counts) in various immune cell subtypes obtained from dataset GSE60424. (C) PubMed query for NUDT16 and inflammation, neutrophils or sepsis‐related literature. No overlaps were found, indicating a probable biomedical knowledge gap. (D) Whole blood from healthy donors (n = 7) post 6h with LPS/PGN or culture medium (Control). NUDT16 expression was assessed by RT‐qPCR and normalized to GAPDH transcript expression. (E) Expression of NUDT16 in cultured whole blood immune cells before and after stimulation for 24 h (expressed as % of parent cell population). (F) Relative abundance of NUDT16 in cultured whole blood expressed as the fold change in frequency parent cell population (stimulated/non‐stimulated). G‐H) Intermediate biological concepts linking indirectly NUDT16 to neutrophils, inflammation or sepsis literature. The most prevalent biological concepts returned were then used in searches against the neutrophil, inflammation or sepsis literature. The extent of the overlap with the NUDT16 literature is shown for the two dominant concepts, ‘RNA decapping’ and ‘ADP ribosylation’