Circulating DNA reveals nucleosome occupancy patterns that are associated with nucleosome-DNA affinity and are affected in cancer
Richaud, M.; Pisareva, E.; Burgat, P.; THIERRY, A.; Colinge, J.
Show abstract
The study of cell-free circulating DNA (cirDNA) fragments (fragmentomics) from liquid biopsies has received increasing attention. By constructing an atlas of these well-positioned nucleosomes, which we called WPNA, we found that their occupancy was associated with histone-DNA affinity, as evidenced by codon usage bias and differences in cirDNA fragment sizes. Moreover, WPNA nucleosome occupancy was different in healthy and cancer samples, thus allowing developing a high-performance machine learning approach for cancer detection (specificity and sensitivity >0.95 for seven cancer types). Cancer influenced WPNA nucleosome occupancy in a global manner, although distinct cancer types retained specific features. WPNA nucleosome occupancy at transcription factor binding sites revealed shared, pan-cancer regulation of transcriptional programs involved in hematopoietic cell differentiation and neutrophil biology, the main cirDNA sources. This work provides new fundamental insights into cirDNA and DNA sequence using cirDNA as a physical readout. It also bares translational significance by disclosing a new high-performance strategy for cancer detection from liquid biopsies.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Cancer-specific CTCF binding facilitates oncogenic transcriptional dysregulation 95%
- Regulatory roles of three-dimensional structures of chromatin domains 95%
- Allele-specific DNA methylation is increased in cancers and its dense mapping in normal plus neoplastic cells increases the yield of disease-associated regulatory SNPs 95%
Similar papers in this journal
- Predicting unrecognized enhancer-mediated genome topology by an ensemble machine learning model 96%
- Human and rat skeletal muscle single-nuclei multi-omic integrative analyses nominate causal cell types, regulatory elements, and SNPs for complex traits 95%
- CRISPR/Cas9 deletions induce adverse on-target genomic effects leading to functional DNA in human cells 95%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.