Long non-coding RNA pairs to assist in diagnosing sepsis

Zheng, Xubin1,2; Leung, Kwong-Sak2; Wong, Man-Hon2; Cheng, Lixin1

2021-04-16

10.1186/s12864-021-07576-4

BMC GENOMICS   影响因子和分区

1471-2164

Background Sepsis 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. Results Cohorts (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. lncRNA(i) > lncRNA(j) in sepsis patients and lncRNA(i) < lncRNA(j) 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. Conclusion Our 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.

Sepsis Diagnostics Signature Long non-coding RNA Relative expression

SCI

英语

第一 ; 通讯

Guangdong Basic and Applied Basic Research Foundation[2019A1515110097]

Biotechnology & Applied Microbiology ; Genetics & Heredity

Biotechnology & Applied Microbiology ; Genetics & Heredity

WOS:000641446800001

BMC

MOLECULAR BIOLOGY & GENETICS

Web of Science

1.Jinan Univ, Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen Peoples Hosp,Clin Med Coll 2, Shenzhen 518020, Peoples R China
2.Chinese Univ Hong Kong, Dept Comp Sci & Engn, Shatin, Hong Kong, Peoples R China

Zheng, Xubin,Leung, Kwong-Sak,Wong, Man-Hon,et al. Long non-coding RNA pairs to assist in diagnosing sepsis[J]. BMC GENOMICS,2021,22(1).

Zheng, Xubin,Leung, Kwong-Sak,Wong, Man-Hon,&Cheng, Lixin.(2021).Long non-coding RNA pairs to assist in diagnosing sepsis.BMC GENOMICS,22(1).

Zheng, Xubin,et al."Long non-coding RNA pairs to assist in diagnosing sepsis".BMC GENOMICS 22.1(2021).