bims-ovdlit 2025-10-12 papers

Issue of 2025–10–12
four papers selected by
Lara Paracchini, Humanitas Research

Nat Rev Genet. 2025 Oct 10.

Clinical use of polygenic risk scores: current status, barriers and future directions.

Genome-wide association studies have identified thousands of single-nucleotide variants that are associated with complex traits, including cardiometabolic diseases, cancers and neurological disorders. Polygenic risk scores (PRSs), which aggregate the effects of these variants, can help to identify individuals who are at increased risk of developing such diseases. As PRSs are typically only weakly associated with conventional risk factors for these diseases, they have incremental predictive value and are beginning to be incorporated into clinical practice to guide early detection and preventive strategies. However, challenges to their use - such as suboptimal precision, poor transferability across diverse populations and low familiarity among patients and providers with the concept of polygenic risk - must be addressed before their broader clinical adoption. This Review explores the current state of the field, highlights key challenges and outlines future directions for the use of PRSs to improve risk prediction and to advance personalized prevention in clinical care.

DOI: https://doi.org/10.1038/s41576-025-00900-8

Microbiol Spectr. 2025 Oct 08. e0320624

Characterization of cervical microbiota in cervical intraepithelial neoplasia and cervical cancer using low-coverage whole genome sequencing.

Tingting Zhang, Fang Gu, Weihua Li, Ruxue Han, Xinyu Liu, Chan Dai, Di Zhang, Hua Li.

This study characterized compositional shifts in cervical microbiota across disease stages from benign conditions through cervical intraepithelial neoplasia (CIN) to cervical cancer (CC) and investigated interactions with high-risk HPV (hr-HPV) infection using species-resolution profiling to identify severity-associated biomarkers. Cervical exfoliated epithelial cells from 50 patients (eight normal/CIN1, 15 CIN2, 19 CIN3, 5 CC) were analyzed using Low-Coverage Whole Genome Sequencing combined with the Ultrasensitive Chromosomal Aneuploidy Detector (UCAD), a technology featuring a two-step normalization framework that systematically converts raw microbial reads into statistically validated abundance deviations. This enables quantitative identification of pathologically relevant microbiota through cohort-wide Z-score benchmarking. Microbial diversity, differential biomarkers, and HPV-microbiota interactions were assessed using Kruskal-Wallis tests, LEfSe, and Random Forest modeling. Results revealed progressive Lactobacillus depletion (e.g., Lactobacillus crispatus: 32.9% in ≤CIN2 vs. 8.8% in CC) and enrichment of pathobionts like Gardnerella and Bacteroides with lesion severity. CC exhibited the highest microbial diversity (Shannon index: CC vs. CIN2, P=0.045), dominated by HPV16 (11.8%), Bacteroides (55.4%), and Porphyromonas (25.2%). LEfSe identified HPV16, HPV35, Parvimonas micra, and Anaerococcus lactolyticus as CC-specific markers, while Random Forest highlighted Mobiluncus curtisii (importance score=2.0) and HPV16 as key discriminators. CC microbiota showed significant Bacteroidetes enrichment (82% at class level) and reduced Firmicutes abundance. These findings suggest carcinogenesis-associated microbial restructuring, marked by Lactobacillus loss, anaerobic proliferation, and HPV16/35 dominance, potentially modulating disease progression. The identified signatures may inform diagnostic development and microbiome-targeted therapies.IMPORTANCEOur study pioneers an LC-WGS/UCAD approach to characterize microbial across the spectrum from benign lesions through precancerous cervical intraepithelial neoplasia to invasive cervical carcinoma. By identifying lesion-specific microbial biomarkers and HPV-associated cofactors, this work advances mechanistic understanding of microbiota-driven oncogenesis and informs future strategies for microbiota-targeted cervical cancer prevention.

Keywords: cervical cancer (CC); cervical intraepithelial neoplasia (CIN); cervical microbiota (CM); low-coverage whole-genome sequencing (LC-WGS); ultrasensitive chromosomal aneuploidy detector (UCAD)

DOI: https://doi.org/10.1128/spectrum.03206-24

Nat Rev Genet. 2025 Oct 08.

Forensic genetics in the omics era.

Manfred Kayser.

Recent advances in forensic genetics, driven by technological innovation coupled with the use of an expanding range of nucleic acid markers, have markedly improved the scope, accuracy and reliability of evidential information obtainable from human biological traces recovered at crime scenes. The majority of these biomarkers have been identified using non-targeted omics approaches, including genomics, transcriptomics, epigenomics and microbiome profiling. Moreover, targeted massively parallel sequencing, in some cases non-targeted whole-genome sequencing, are being applied to the analyses of biological trace material. These approaches and methods are being used for the identification of perpetrators (including monozygotic twins), their relatives or victims of criminal activities; the prediction of phenotypic and behavioural traits of unknown individuals; and the determination of trace characteristics, including tissue type and time of deposition.

DOI: https://doi.org/10.1038/s41576-025-00896-1