bims-fragic 2025-09-14 papers

Issue of 2025–09–14
two papers selected by
Laura Mannarino, Humanitas Research

Cell Rep Methods. 2025 Jul 21. pii: S2667-2375(25)00119-5. [Epub ahead of print]5(7): 101083

Fragment dispersity index analysis of cfDNA fragments reveals chromatin accessibility and enables early cancer detection.

Yunze Wang, Yuying Hou, Zhankun Xiong, Libo Lu, Zhanxiang Zong, Bo Wang, Hebing Chen, Wen Zhang, Xionghui Zhou.

We introduce a cell-free DNA (cfDNA) fragmentation pattern: the fragment dispersity index (FDI), which integrates information on the distribution of cfDNA fragment ends with the variation in fragment coverage, enabling precise characterization of chromatin accessibility in specific regions. The FDI shows a strong correlation with chromatin accessibility and gene expression, and regions with high FDI are enriched in active regulatory elements. Using whole-genome cfDNA data from five datasets, we developed and validated the FDI-oncology model, which demonstrates robust performance in early cancer diagnosis, subtyping, and prognosis. Case studies reveal that key cancer genes such as HER2 and TP53 exhibit significantly different FDIs between cancer and control samples. Simulation experiments suggest that deep targeted sequencing of a small number of regions can achieve high diagnostic efficiency.

Keywords: CP: cancer biology; CP: systems biology; cancer early detection; cfDNA; liquid biopsy; machine learning

DOI: https://doi.org/10.1016/j.crmeth.2025.101083

NAR Genom Bioinform. 2025 Sep;7(3): lqaf119

Cell-free DNA as a potential alternative to genomic DNA in genetic studies.

Jingyu Zeng, Huanhuan Zhu, Yu Wang, Guodan Zeng, Panhong Liu, Rijing Ou, Xianmei Lan, Yuhui Zheng, Chenhui Zhao, Linxuan Li, Haiqiang Zhang, Jianhua Yin, Mingzhi Liao, Yan Zhang, Xin Jin.

Next-generation sequencing has greatly advanced genomics, enabling large-scale studies of population genetics and complex traits. Genomic DNA (gDNA) from white blood cells has traditionally been the main data source, but cell-free DNA (cfDNA), found in bodily fluids as fragmented DNA, is increasingly recognized as a valuable biomarker in clinical and genetic studies. However, a direct comparison between cfDNA and gDNA has not been fully explored. In this study, we analyzed cfDNA and gDNA from 186 healthy individuals, using the same sequencing platform. We compared sequencing quality, variant detection, allele frequencies (AF), genotype concordance, population structure, and genomic association results (genome-wide association study and expression quantitative trait locus). While cfDNA showed higher duplication rates and lower effective sequencing depth, both DNA types displayed similar quality metrics at the same depth. We also observed that significant depth differences between cfDNA and gDNA were mainly found in centromeric regions. While gDNA identified more variants with more uniform coverage, AF spectra, population structure, and genomic associations were largely consistent between the two DNA types. This study provides a detailed comparison of cfDNA and gDNA, highlighting the potential of cfDNA as an alternative to gDNA in genomic research. Our findings could serve as a reference for future studies on cfDNA and gDNA.

DOI: https://doi.org/10.1093/nargab/lqaf119