Long non-coding RNA pairs to assist in diagnosing sepsis

BMC Genomics

Man-Hon Wong¹  Kwong-Sak Leung¹  Lixin Cheng²  Xubin Zheng³ 

[1] Department of Computer Science and Engineering, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong;Shenzhen People’s Hospital, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medicine College of Jinan University, 518020, Shenzhen, China;Shenzhen People’s Hospital, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medicine College of Jinan University, 518020, Shenzhen, China;Department of Computer Science and Engineering, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong;

关键词: Sepsis;    Diagnostics;    Signature;    Long non-coding RNA;    Relative expression;   

DOI  :  10.1186/s12864-021-07576-4

来源: Springer

【 摘 要 】

BackgroundSepsis is the major cause of death in Intensive Care Unit (ICU) globally. Molecular detection enables rapid diagnosis that allows early intervention to minimize the death rate. Recent studies showed that long non-coding RNAs (lncRNAs) regulate proinflammatory genes and are related to the dysfunction of organs in sepsis. Identifying lncRNA signature with absolute abundance is challenging because of the technical variation and the systematic experimental bias.ResultsCohorts (n = 768) containing whole blood lncRNA profiling of sepsis patients in the Gene Expression Omnibus (GEO) database were included. We proposed a novel diagnostic strategy that made use of the relative expressions of lncRNA pairs, which are reversed between sepsis patients and normal controls (eg. lncRNAi > lncRNAj in sepsis patients and lncRNAi < lncRNAj in normal controls), to identify 14 lncRNA pairs as a sepsis diagnostic signature. The signature was then applied to independent cohorts (n = 644) to evaluate its predictive performance across different ages and normalization methods. Comparing to common machine learning models and existing signatures, SepSigLnc consistently attains better performance on the validation cohorts from the same age group (AUC = 0.990 & 0.995 in two cohorts) and across different groups (AUC = 0.878 on average), as well as cohorts processed by an alternative normalization method (AUC = 0.953 on average). Functional analysis demonstrates that the lncRNA pairs in SepsigLnc are functionally similar and tend to implicate in the same biological processes including cell fate commitment and cellular response to steroid hormone stimulus.ConclusionOur study identified 14 lncRNA pairs as signature that can facilitate the diagnosis of septic patients at an intervenable point when clinical manifestations are not dramatic. Also, the computational procedure can be generalized to a standard procedure for discovering diagnostic molecule signatures.

【 授权许可】

CC BY