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Advancing sepsis clinical research: harnessing transcriptomics for an omics-based strategy - a comprehensive scoping review

Rashid, Asrar; Al-Obeidat, Feras; Kanthimathinathan, Hari Krishnan; Benakatti, Govind; Hafez, Wael; Ramaiah, Raghu; Brierley, Joe; Hanisch, Benjamin; Khilnani, Praveen; Koutentis, Christos; Brusletto, Berit S.; Toufiq, Mohammed; Hussain, Zain; Vyas, Harish; Malik, Zainab A; Schumacher, Maike; Malik, Rayaz A; Deshpande, Shriprasad; Quraishi, Nasir; Kadwa, Raziya; Sarpal, Amrita; Shaikh, M. Guftar; Sharief, Javed; Zaki, Syed Ahmed; Phatak, Rajesh; Deep, Akash; Al-Dubai, Ahmed; Hussain, Amir


Asrar Rashid

Feras Al-Obeidat

Hari Krishnan Kanthimathinathan

Govind Benakatti

Wael Hafez

Raghu Ramaiah

Joe Brierley

Benjamin Hanisch

Praveen Khilnani

Christos Koutentis

Berit S. Brusletto

Mohammed Toufiq

Zain Hussain

Harish Vyas

Zainab A Malik

Maike Schumacher

Rayaz A Malik

Shriprasad Deshpande

Nasir Quraishi

Raziya Kadwa

Amrita Sarpal

M. Guftar Shaikh

Javed Sharief

Syed Ahmed Zaki

Rajesh Phatak

Akash Deep


Sepsis continues to be recognized as a significant global health challenge across all ages and is characterized by a complex pathophysiology. In this scoping review, PRISMA-ScR guidelines were adhered to, and a transcriptomic methodology was adopted, with the protocol registered on the Open Science Framework. We hypothesized that gene expression analysis could provide a foundation for establishing a clinical research framework for sepsis. A comprehensive search of the PubMed database was conducted with a particular focus on original research and systematic reviews of transcriptomic sepsis studies published between 2012 and 2022. Both coding and non-coding gene expression studies have been included in this review. An effort was made to enhance the understanding of sepsis at the mRNA gene expression level by applying a systems biology approach through transcriptomic analysis. Seven crucial components related to sepsis research were addressed in this study: endotyping (n = 64), biomarker (n = 409), definition (n = 0), diagnosis (n = 1098), progression (n = 124), severity (n = 451), and benchmark (n = 62). These components were classified into two groups, with one focusing on Biomarkers and Endotypes and the other oriented towards clinical aspects. Our review of the selected studies revealed a compelling association between gene transcripts and clinical sepsis, reinforcing the proposed research framework. Nevertheless, challenges have arisen from the lack of consensus in the sepsis terminology employed in research studies and the absence of a comprehensive definition of sepsis. There is a gap in the alignment between the notion of sepsis as a clinical phenomenon and that of laboratory indicators. It is potentially responsible for the variable number of patients within each category. Ideally, future studies should incorporate a transcriptomic perspective. The integration of transcriptomic data with clinical endpoints holds significant potential for advancing sepsis research, facilitating a consensus-driven approach, and enabling the precision management of sepsis.

Journal Article Type Article
Acceptance Date Nov 27, 2023
Online Publication Date Dec 21, 2023
Publication Date 2024
Deposit Date Dec 22, 2023
Publicly Available Date Jan 4, 2024
Journal Informatics in Medicine Unlocked
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 44
Article Number 101419
Keywords Sepsis, Transcriptomics, Omic, Sepsis definition, Biomark, Endotype, Sepsis progression, Sepsis severity
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