Charting Extracellular Transcriptomes in The Human Biofluid RNA Atlas

Area of Science:

• Molecular Biology
• Biochemistry
• Genomics

Background:

• Extracellular RNAs (exRNAs) in biofluids are promising disease biomarkers.
• Research predominantly focuses on blood, overlooking other potentially informative biofluids.

Purpose of the Study:

• To create a comprehensive atlas of messenger, circular, and small RNA transcriptomes across 20 human biofluids.
• To compare RNA concentrations and profiles across different biofluids.
• To identify biofluids suitable for specific disease biomarker monitoring.

Main Methods:

• Profiling of messenger, circular, and small RNA transcriptomes from 20 human biofluids.
• Utilizing synthetic spike-in controls for accurate RNA quantification and cross-biofluid comparison.
• Analysis of four independent disease cohorts for biomarker validation.

Main Results:

• A 10,000-fold variation in RNA concentration was observed across the 20 biofluids.
• Circular RNA fractions were generally higher in biofluids than in tissues.
• Each biofluid exhibited unique RNA signatures enriched from specific tissue and cell types.
• Differential RNAs were identified between disease and control groups in validation cohorts.

Conclusions:

• The developed biofluid RNA atlas facilitates informed selection of biofluids for disease biomarker studies.
• Extracellular RNA profiles in biofluids hold significant potential for non-invasive disease diagnostics.
• Publicly available spike-normalized data supports further research and exploration of biofluid biomarkers.