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

Darawan Rinchai,Alberto Ballestrero,Andrea De Maria,Damien Chaussabel,Mohammed Toufiq,Zohreh Tatari-Calderone,Mohamed Alfaki,Matteo Bassetti,Sara Deola,Gabriele Zoppoli,Davide Bedognetti,Tobias Brummaier,Basirudeen Syed Ahamed Kabeer,Ricardo Branco,Benjamin Tang,Nicole Baldwin,Matthew C Altman,Mathieu Garand

doi:10.1186/s12967-020-02456-z

Abstract

BackgroundCovid-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 targeted blood transcriptome panels for profiling the immune response to SARS-CoV-2 infection.MethodsWe 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.ResultsAs a proof of principle, we designed three targeted blood transcript panels, each with a different translational connotation: immunological relevance, therapeutic development relevance and SARS biology relevance.ConclusionAltogether 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.

Highlights

Covid-19 morbidity and mortality are associated with a dysregulated immune response
Mapping Covid‐19 blood transcriptome signatures against a pre‐existing reference set of transcriptional modules Changes in blood transcript abundance in response to Severe Acute Respiratory Syndrome (SARS)-CoV-2 infection have far been reported in two different studies
We employed a pre-established repertoire of 382 transcriptional modules (Fig. 1a) to map changes observed in Covid-19 patients

Summary

Introduction

Covid-19 morbidity and mortality are associated with a dysregulated immune response. Tools are needed to enhance existing immune profiling capabilities in affected patients. We aimed to develop an approach to support the design of targeted blood transcriptome panels for profiling the immune response to SARSCoV-2 infection. Blood transcriptome profiling involves measuring the abundance of circulating leukocyte RNA on a genome-wide scale via RNA sequencing [5]. The possibility of implementing this approach on large scales to ensure immediate translational potential is limited. Such unbiased omics profiling data might rather be leveraged to inform the development of more practical, scalable and targeted transcriptional profiling assays. These assays could in turn serve to significantly bolster existing immune profiling capacity

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