Alfaki, M. | Search bioRxiv

bioRxiv2020

A modular framework for the development of targeted Covid-19 blood transcript profiling panels

Covid-19 morbidity and mortality are associated with a dysregulated immune response. Tools are needed to enhance existing immune profiling capabilities in affected patients. Here we aimed to develop an approach to support the design of focused blood transcriptome panels for profiling the immune response to SARS-CoV-2 infection. We designed a pool of candidates based on a pre-existing and well-characterized repertoire of blood transcriptional modules. Available Covid-19 blood transcriptome data was also used to guide this process. Further selection steps relied on expert curation. Additionally, we developed several custom web applications to support the evaluation of candidates. As a proof of principle, we designed three targeted blood transcript panels, each with a different translational connotation: therapeutic development relevance, SARS biology relevance and immunological relevance. Altogether the work presented here may contribute to the future expansion of immune profiling capabilities via targeted profiling of blood transcript abundance in Covid-19 patients.

immunology↗

bioRxiv2018

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↗