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Blood RNA signature RISK4LEP predicts leprosy years before clinical onset
- Source :
- EBioMedicine, EBioMedicine, 68:103379. Elsevier, EBioMedicine, 68. ELSEVIER, EBioMedicine, Vol 68, Iss, Pp 103379-(2021)
- Publication Year :
- 2021
- Publisher :
- Elsevier, 2021.
-
Abstract
- Background: Leprosy, a chronic infectious disease caused by Mycobacterium leprae, is often late- or misdiagnosed leading to irreversible disabilities. Blood transcriptomic biomarkers that prospectively predict those who progress to leprosy (progressors) would allow early diagnosis, better treatment outcomes and facilitate interventions aimed at stopping bacterial transmission. To identify potential risk signatures of leprosy, we collected whole blood of household contacts (HC, n=5,352) of leprosy patients, including individuals who were diagnosed with leprosy 4-61 months after sample collection. Methods: We investigated differential gene expression (DGE) by RNA-Seq between progressors before presence of symptoms (n=40) and HC (n=40), as well as longitudinal DGE within each progressor. A prospective leprosy signature was identified using a machine learning approach (Random Forest) and validated using reverse transcription quantitative PCR (RT-qPCR). Findings: Although no significant intra-individual longitudinal variation within leprosy progressors was identified, 1,613 genes were differentially expressed in progressors before diagnosis compared to HC. We identified a 13-gene prospective risk signature with an Area Under the Curve (AUC) of 95.2%. Validation of this RNA-Seq signature in an additional set of progressors (n=43) and HC (n=43) by RT-qPCR, resulted in a final 4-gene signature, designated RISK4LEP (MT-ND2, REX1BD, TPGS1, UBC) (AUC=86.4%). Interpretation: This study identifies for the first time a prospective transcriptional risk signature in blood predicting development of leprosy 4 to 61 months before clinical diagnosis. Assessment of this signature in contacts of leprosy patients can function as an adjunct diagnostic tool to target implementation of interventions to restrain leprosy development. Funding: This study was supported by R2STOP Research grant, the Order of Malta-Grants-for-Leprosy-Research, the Q.M. Gastmann-Wichers Foundation and the Leprosy Research Initiative (LRI) together with the Turing Foundation (ILEP# 702.02.73 and # 703.15.07).
- Subjects :
- 0301 basic medicine
Oncology
Male
Medicine (General)
Research paper
Machine Learning
0302 clinical medicine
Gene Regulatory Networks
RNA-Seq
Prospective Studies
Child
Mycobacterium leprae
Diagnostics
Whole blood
biology
Transmission (medicine)
Area under the curve
General Medicine
Middle Aged
Real-time polymerase chain reaction
030220 oncology & carcinogenesis
Disease Progression
Biomarker (medicine)
Medicine
Female
Leprosy
Adult
medicine.medical_specialty
Adolescent
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Young Adult
R5-920
SDG 3 - Good Health and Well-being
Internal medicine
medicine
Humans
Transcriptomics
Aged
business.industry
Sequence Analysis, RNA
Gene Expression Profiling
Biomarker
Gene signature
medicine.disease
biology.organism_classification
030104 developmental biology
Gene Expression Regulation
Case-Control Studies
business
Prediction
Biomarkers
Subjects
Details
- Language :
- English
- ISSN :
- 23523964
- Volume :
- 68
- Database :
- OpenAIRE
- Journal :
- EBioMedicine
- Accession number :
- edsair.doi.dedup.....aa7f2e2f6a6f4ef4f315f3fd6fdb0e66