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Updated: May 12, 2025
Targeted RNA Sequencing Assay to Characterize Gene Expression and Genomic Alterations
Published on: August 4, 2016
Peak analysis of cell-free RNA finds recurrently protected narrow regions with clinical potential
Pengfei Bao1,2,3, Taiwei Wang1,4,5,6, Xiaofan Liu1,2
1MOE Key Laboratory of Bioinformatics, State Key Lab of Green Biomanufacturing, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
Background:
Cell-free RNAs (cfRNAs) can be detected in biofluids and have emerged as valuable disease biomarkers. Accurate identification of the fragmented cfRNA signals, especially those originating from pathological cells, is crucial for understanding their biological functions and clinical value. However, many challenges still need to be addressed for their application, including developing specific analysis methods and translating cfRNA fragments with biological support into clinical applications.
Results:
We present cfPeak, a novel method combining statistics and machine learning models to detect the fragmented cfRNA signals effectively. When test in real and artificial cfRNA sequencing (cfRNA-seq) data, cfPeak shows an improved performance compared with other applicable methods. We reveal that narrow cfRNA peaks preferentially overlap with protein binding sites, vesicle-sorting sites, structural sites, and novel small non-coding RNAs (sncRNAs). When applied in clinical cohorts, cfPeak identified cfRNA peaks in patients' plasma that enable cancer detection and are informative of cancer types and metastasis.
Conclusions:
Our study fills the gap in the current small cfRNA-seq analysis at fragment-scale and builds a bridge to the scientific discovery in cfRNA fragmentomics. We demonstrate the significance of finding low abundant tissue-derived signals in small cfRNA and prove the feasibility for application in liquid biopsy.
