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The Blood RNA Stability Atlas: defining temporal structure and trait-state programs in the human whole-blood
Will C Baltazar1,2, Robert O Messing1, Laura B Ferguson1,3
1The Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin Dell Medical School, Austin, TX.
Biorxiv : the Preprint Server for Biology
|July 17, 2026
Summary
Whole-blood RNA biomarkers are crucial for health monitoring. This study defines "trait" (stable) and "state" (dynamic) blood RNA categories, revealing a genetic basis for stable RNAs and informing biomarker selection for disease diagnosis.
Area of Science:
- Genomics
- Molecular Biology
- Biomarker Discovery
Background:
- Whole-blood RNA biomarkers are vital for disease diagnosis and monitoring.
- Biomarker utility relies on both abundance and temporal stability, a factor often overlooked in design.
- Understanding blood transcriptome dynamics is key for accurate health assessments.
Purpose of the Study:
- To quantify the temporal stability of whole-blood RNA transcripts.
- To classify transcripts into stable ('trait') and dynamic ('state') categories.
- To establish a framework for biomarker prioritization based on RNA stability.
Main Methods:
- Analyzed 968 longitudinal whole-blood transcriptomes from 165 healthy individuals across diverse studies.
- Employed variance partitioning, repeatability, and differential expression analysis to assess RNA stability.
- Integrated transcriptomic data with genetic datasets (eQTLs, GWAS) to explore stability's genetic and disease relevance.
Main Results:
- Quantified temporal stability for 6,064 RNAs, classifying them into 'trait' (1,118) and 'state' (1,504) categories.
- Identified 'trait' RNAs as having stable within-individual abundance with a genetic basis (enriched for eGenes).
- Found 'state' RNAs exhibit context-dependent variation, enriched in translation and RNA-binding pathways, with 72% linked to eQTLs and disease traits.
Conclusions:
- Temporal stability is a fundamental property of the blood transcriptome.
- The Blood RNA Stability Atlas provides a resource for distinguishing stable from dynamic RNAs.
- This framework aids in selecting appropriate blood RNA biomarkers for clinical applications and research.
Keywords:
biomarker reproducibilitylongitudinal RNA measuresmRNA variabilitytranscriptomic biomarker discoverywhole-blood transcriptomicsMore Related Videos
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