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Bedognetti, D.

Publications and source records attributed to Bedognetti, D..

20 records · Page 2Linked to original sources

Characterizing blood modular transcriptional repertoire perturbations in patients with RSV infection: a hands-on workshop using public datasets as a source of training material

Biomarkers to assess the severity of acute respiratory syncytial virus (RSV) infection are needed. We conducted a meta-analysis of 490 unique profiles from six public RSV blood transcriptome datasets. A repertoire of 382 well-characterized transcriptional modules was used to define dominant host responses to RSV infection. The consolidated RSV cohort was stratified according to four traits: "interferon response" (IFN), "neutrophil-driven inflammation" (Infl), "cell cycle" (CC), and "erythrocytes" (Ery). Eight prevalent blood transcriptome phenotypes were thus identified. Among those three Ery+ phenotypes comprised higher proportions of patients requiring intensive care. We posit that the erythrocyte module is linked to an overabundance of immunosuppressive erythroid cells that might underlie progression to severe RSV infection. These findings outline potential priority areas for biomarker development and investigations into the immune biology of RSV infection. The approach that was employed here will also permit to delineate prevalent blood transcriptome phenotypes in other settings.

immunology↗

The abundance of Nudix hydrolase 16 transcripts is elevated in human sepsis: perspectives gained during a hands-on reductionist investigation workshop.

A hands-on training workshop was devised with omics data used as source material to emulate reductionist investigation approaches. NUDT16, a member of the Nudix hydrolase family was selected as a candidate gene on the basis of: 1) it being upregulated in neutrophils exposed in vitro to serum of patients with sepsis, AND 2) the absence of overlap between the NUDT16 and sepsis, inflammation or neutrophil literature. We next sought to corroborate the initial finding in five public transcriptome sepsis datasets in which NUDT16 transcript levels were measured. In each of these dataset NUDT16 transcript abundance was found to be significantly increased in septic patients in vivo in comparison to uninfected controls. Next, biological concepts were extracted from the NUDT16 literature. The main concepts to emerge from profiling this literature were RNA decapping, inosine triphosphate, and inosine diphosphate. Through these concepts, indirect links could be established between NUDT16 and the sepsis/inflammation/neutrophil literature. A potential role for NUDT16 could, in turn, be inferred in the degradation of mRNAs in activated neutrophils. Follow on experiments that would be necessary in order to further explore such inference are discussed.

immunology↗