Biology subjects

Le, S. V.

Publications and source records attributed to Le, S. V..

4 recordsLinked to original sources

bioRxiv2026

First-Trimester Non-Invasive Prediction of Preterm Birth Using Cell-Free DNA Fragmentomics

ObjectiveTo develop and validate a cell-free DNA (cfDNA) fragmentomic classifier for the early prediction of spontaneous preterm birth (PTB) using routine first-trimester non-invasive prenatal testing (NIPT) data. MethodsA nested case-control study was conducted within a prospective multicenter Vietnamese cohort comprising 286 pregnancies, including 82 spontaneous PTB cases and 204 term controls. Maternal plasma cfDNA collected during routine first-trimester NIPT (median gestational age, 12 weeks) was sequenced to a depth of approximately 20 million reads per sample. Five fragmentomic feature categories including copy number alterations, end-motif composition, nucleosome distance, fragment length, and joint fragment-lengthxend-motif were evaluated for PTB prediction. Machine learning classifiers were developed in a training cohort (n = 228, 65 PTB vs 163TB) and tested in a validation cohort (n = 58, 17 PTB vs 41 TB). ResultsAmong the five fragmentomic feature classes evaluated, 4-mer end-motif (EM) profiles exhibited the most pronounced differences between PTB and term control samples. Consistent with these findings, the EM-based classifier demonstrated the highest discriminative performance in the validation cohort, achieving an AUC of 0.970 (95% CI, 0.912-1.000). At a specificity >90%, the model achieved a sensitivity of 94% (95% CI, 78-100%). ConclusionThese findings demonstrate that cfDNA EM signatures derived from routine first-trimester NIPT can accurately identify pregnancies at risk of spontaneous preterm birth, without additional blood collection or sequencing, thereby extending the clinical utility of existing prenatal screening infrastructure. KEY POINTSO_ST_ABSWhat is already known about this topic?C_ST_ABSO_LICurrent first-trimester prediction strategies based on maternal characteristics, cervical length, and biochemical markers have limited predictive accuracy, particularly in nulliparous women. C_LIO_LIExisting cfDNA-based approaches have shown only modest performance or require additional assays, limiting clinical applicability. C_LI What does this study add?O_LIExisting NIPT sequencing data can be repurposed (without additional blood sampling or sequencing) for accurate prediction of spontaneous preterm birth (AUC=0.970). C_LIO_LIA classifier employing 4-mer end-motif (EM) profiles achieved an AUC of 0.970. At a specificity >90%, the model achieved a sensitivity of 94%. C_LI

genomics↗

bioRxiv2024

Molecular Phylogeny and Cryptic Morphology: A Combined Approach to Taxonomic Novelties in Polycarpaea (Caryophyllaceae) from Vietnam

Three new species of Polycarpaea from Vietnam, P. vanana, P. chungana, P. duongana are described and illustrated based on evidence of molecular sequence data from two markers (ITS1-5.8S-ITS2 and rps16) and combined morphological characteristics. Polycarpaea vanana is closely related to Polycarpaea gaudichaudi, P. arenaria, P. duongana but differs by its stem glabrous, leaf ovate to elliptic, glabrous, ovary oblong ovoid, base obtuse, apex attenuate, capsule oblong void, 3.8 mm long. P. duongana differs from the three species mentioned above by its stem being densely villous, leaf spathulate, ciliate, ovary ovoid, base acute, apex obtuse, capsule ovoid, 1.2 mm long. Polycarpaea chungana is most similar to P. lignosa but differs in having leaf oblong or linear, sparse ciliate, sepal and petal apex deeply concaved or slightly bifid, ovary ovoid, ovoid, 0.8-1.0 mm long. Furthermore, the achievements of analysis using molecular data on the systematic positions of 7 other species are results that have not been in previous molecular analyses.

plant biology↗

bioRxiv2019

PRC2 activates interferon-stimulated genes indirectly by repressing miRNAs in glioblastoma

Polycomb repressive complex 2 (PRC2) is a chromatin binding complex that represses gene expression by methylating histone H3 at K27 to establish repressed chromatin domains. PRC2 can either regulate genes directly through the methyltransferase activity of its component EZH2 or indirectly by regulating other gene regulators. Gene expression analysis of glioblastoma (GBM) cells lacking EZH2 showed that PRC2 regulates hundreds of interferon-stimulated genes (ISGs). We found that PRC2 directly represses several ISGs and also indirectly activates a distinct set of ISGs. Assessment of EZH2 binding proximal to miRNAs showed that PRC2 directly represses miRNAs encoded in the chromosome 14 imprinted DLK1-DIO3 locus. We found that repression of this locus by PRC2 occurs in immortalized GBM-derived cell lines as well as in primary bulk tumors from GBM and anaplastic astrocytoma patients. Through repression of these miRNAs and several other miRNAs, PRC2 activates a set of ISGs that are targeted by these miRNAs. This PRC2-miRNA-ISG network is likely to be important in regulating gene expression programs in GBM.

molecular biology↗

bioRxiv2018

MicroRNAs reinforce repression of PRC2 transcriptional targets independently and through a feed-forward regulatory network with PRC2

Gene expression can be regulated at multiple levels, but it is not known if and how there is broad coordination between regulation at the transcriptional and post-transcriptional levels. Transcription factors and chromatin regulate gene expression transcriptionally, while microRNAs (miRNAs) are small regulatory RNAs that function post-transcriptionally. Systematically identifying the post-transcriptional targets of miRNAs and the mechanism of transcriptional regulation of the same targets can shed light on regulatory networks connecting transcriptional and post-transcriptional control. We used iCLIP (individual crosslinking and immunoprecipitation) for the RISC (RNA-induced silencing complex) component AGO2 and global miRNA depletion to identify genes directly targeted by miRNAs. We found that PRC2 (Polycomb repressive complex 2) and its associated histone mark, H3K27me3, is enriched at hundreds of miRNA-repressed genes. We show that these genes are directly repressed by PRC2 and constitute a significant proportion of direct PRC2 targets. For just over half of the genes co-repressed by PRC2 and miRNAs, PRC2 promotes their miRNA-mediated repression by increasing expression of the miRNAs that are likely to target them. miRNAs also repress the remainder of the PRC2 target genes, but independently of PRC2. Thus, miRNAs post-transcriptionally reinforce silencing of PRC2-repressed genes that are inefficiently repressed at the level of chromatin, by either forming a feed-forward regulatory network with PRC2 or repressing them independently of PRC2.

genomics↗