Biology subjects

Tran, M. H.

Publications and source records attributed to Tran, M. H..

8 recordsLinked to original sources

bioRxiv2026

A Practical Framework for Constructing Population-Specific and Alternate-Contig-Aware Genome References: A case study of Vietnam

Current studies in human genomics typically rely on the standard genome reference GRCh38 which is known to be biased toward populations of European ancestry and therefore has limitations when applied to other populations. Although various graph-based pangenome references were constructed for several populations to deal with this bias, their usage in practice is currently still limited compared to linear genome references. Here we present a framework for constructing a population-specific genome reference using GRCh38 as backbone with alternate-contig awareness to enhance genomic data analysis in the target population. We demonstrated the advantages of our framework using both public and in-house Vietnamese whole-genome sequencing (WGS) datasets. Genomic variants derived from high-coverage WGS data of the 1000 Vietnamese Genomes Project (VN1K) were imported into our framework to build a Vietnamese-specific Genome Reference (VGR). VGR was then compared to GRCh38 in read alignment and variant calling using high-coverage WGS data of 99 Vietnamese individuals (KHV) from the 1000 Genomes Project (1kGP). Using Omni array genotyping data from 99 KHV samples as an independent benchmark, we found that VGR improved variant-calling precision and reduced false-positive calls compared to GRCh38. Our framework could be easily used for other populations as long as they have a variant database similar to VN1K. Our code is publicly available at github.com/VinGenome/VGR

genomics↗

bioRxiv2025

BAR-CAT: Targeted Recovery of Synthetic Genes via Barcode-Directed CRISPR-dCas9 Enrichment

Modern gene-synthesis platforms let us probe protein function and genome biology at unprecedented scale. Yet in large, diverse gene libraries the proportion of error-free constructs decreases with length due to the propagation of oligo synthesis errors. To rescue these rare, error-free molecules we developed BAR-CAT (Barcode-Assisted Retrieval CRISPR-Activated Targeting), an in-vitro enrichment method that couples unique PAM-adjacent 20-nt barcodes to each library member and uses multiplexed dCas9-sgRNA complexes to fish out the barcodes corresponding to perfect assemblies. After a single 15-min reaction and optimized wash regime (BAR-CAT v1.0), three low-abundance targets in a 300, 000-member test library were enriched 600-fold, greatly reducing downstream requirements. When applied to 384x and 1, 536x member DropSynth gene libraries, BAR-CAT retrieved up to 122-fold enrichment for 12 targets and revealed practical limits imposed by sgRNA competition and library complexity, which now guide ongoing protocol scaling. By eliminating laborious clone-by-clone validation and working directly on plasmid libraries, BAR-CAT provides a versatile platform for recovering perfect synthetic genes, subsetting large libraries, and ultimately lowering the cost of functional genomics at scale.

synthetic biology↗

bioRxiv2025

VN1K: a genome graph-based and function-driven multi-omics and phenomics resource for the Vietnamese population

Vietnam, the 16th most populated nation, remains profoundly underrepresented in global genomic databases. Here, we present VN1K, a first-ever comprehensive and well-curated resource of multi-omics data with a wide-range of phenotypic information of 1,011 unrelated Vietnamese individuals. High-depth short-read whole-genome sequencing data were generated for all samples along with various - omic data, including microarray, long-read whole-genome sequencing, and RNA sequencing. Using a high-sensitivity variant detection pipeline, which included a pangenome graph reference and a deep-learning framework, we identified nearly 40 million variants of which 8.5 million are novel with nearly 900 thousand short insertions/deletions and 39 thousand structural variants. Specifically, VN1K featured a first-ever whole-genome methylation profile based on long read sequencing. A genotype imputation panel was also created with the highest accuracy on the Vietnamese population. Variants with significantly different allele frequencies in the Vietnamese population compared to others were found to be functionally significant, especially in genes associated with immune diseases (HLA-B, KIR3DL3, KIR2DL1, KIR2DL4) or drug responses (CYP2C19, CYP2D6, VKORC1, CYP2B6). We were also able to map various loci related to hepatitis B virus infection as well as six disease traits, including triglyceride levels, LDL-C, serum glucose levels, HbA1c, and levels of two liver enzymes (ALT and AST). VN1K dataset is accessible via genome.vinbigdata.org, an integrated platform with both linear and graph-based genome browser for facilitating data exploration, research, and applications in precision medicine.

genomics↗

bioRxiv2024

Cytotoxic activity against human leukemia cells of Kaempferol-3-O-rhamnoside from Vietnamese Schima wallichii (DC.) Korth: A combination of in vitro and in silico insights

In the investigation of the cytotoxic activity against leukemia cells of Vietnamese medicinal plants, we identified the extract of Schima wallichii (DC.) Korth as capable of inhibiting several leukemia cell lines. In this study, we isolated a main compound as kaempferol-3-O-rhamnoside, marking the first report of this compound being isolated from the stem of Schima wallichii collected in Vietnam. In in vitro experiments, kaempferol-3-O-rhamnoside exhibited cytotoxic effects on three leukemia cell lines, HL-60 and KG-1. Regarding its mechanism of action, the compound effectively inhibited growth of HL-60 and KG-1 leukemia cell lines by activating caspase-3 and caspase-9 in both cell lines. Additionally, kaempferol-3-O-rhamnoside upregulated the pro-apoptotic protein Bax while downregulating the anti-apoptotic protein Bcl-2 in these cell lines. In silico experiments revealed that docking simulations showed kaempferol-3-O-rhamnoside binds to both the allosteric site of procaspase-3 and the active site of PARP1, with binding energies of -7.36 and -10.76 kcal/mol, respectively. Kaempferol-3-O-rhamnoside demonstrated stable binding affinity with PARP1, characterized by significant hydrogen bonding, hydrophobic interactions, and pi-stacking in the molecular dynamic simulations. These results suggest that kaempferol-3-O-rhamnoside has the potential PARP1 inhibitor, making it a promising candidate for targeting leukemia cells. Moreover, it provides evidence for considering this compound in drug discovery and development targeting PARP1-related pathways.

pharmacology and toxicology↗

bioRxiv2024

Supervised non-negative matrix factorization on cell-free DNA fragmentomic features enhances early cancer detection

BackgroundCell-free circulating DNA (cfDNA) fragments exhibit non-random patterns in their length (FLEN), end-motif (EM), and distance to nucleosome position (ND). While these cfDNA features have shown promise as inputs for machine learning and deep learning models in early cancer detection, most studies utilize them as raw inputs, overlooking the potential benefits of pre-processing to extract cancer-specific features. This study aims to enhance cancer detection accuracy by developing a novel approach to feature extraction from cfDNA fragmentomics. MethodsWe implemented a supervised non-negative matrix factorization (SNMF) algorithm to generate embedding vectors capturing cancer-specific signals within cfDNA fragmentomic features. These embeddings served as input for a machine learning model to classify cancer patients from healthy individuals. ResultsWe validated our framework using two datasets: an in-house cohort of 431 cancer patients and 442 healthy individuals (dataset 1), and a published cohort comprising 90 hepatocellular carcinoma (HCC) patients and 103 individuals with cirrhosis or hepatitis B (dataset 2). In dataset 1, we achieved an AUC of 94% in pan-cancer detection. In dataset 2, our framework achieved an AUC of 100% for HCC vs healthy classification, 99% for HCC vs non-HCC patients classification, and 96% for identifying HCC patients among a mixed group of non-HCC patients and healthy donors. ConclusionThis study demonstrates the efficiency of SNMF-transformed features in improving both pan-cancer detection and specific HCC detection. Our approach offers a significant advancement in leveraging cfDNA fragmentomics for early cancer detection, potentially enhancing diagnostic accuracy in clinical settings.

bioinformatics↗

bioRxiv2023

A study of genetic variants associated with skin traits in the Vietnamese population

BackgroundMost skin-related traits have been studied from Caucasian genetic background. A comprehensive study on skin-associated genetic effects on under-represented populations like Vietnam is needed to fill the gaps in the field. ObjectivesTo develop a computational pipeline to predict the effect of genetic factors on skin traits using public data (GWAS catalogs and whole genome sequencing (WGS) data of 1000 genomes project-1KGP) and in-house Vietnamese data (WGS and genotyping by SNP array). By using this information we may have a better understanding of the susceptibility of Vietnamese people. MethodsVietnamese cohorts of whole genome sequencing (WGS) of 1008 healthy individuals for the reference and 96 genotyping samples (which do not have any skin cutaneous issues) by Infinium Asian Screening Array-24 v1.0 BeadChip were employed to predict skin-associated genetic variants of 25 skin-related and micronutrients requirement traits in population analysis and correlation analysis. Simultaneously, we compared the landscape of cutaneous issues of Vietnamese people with other populations by assessing their genetic profiles. ResultsThe skin-related genetic profile of Vietnamese cohorts is similar at most with East Asian (JPT: Fst=0.036, CHB: Fst=0.031, CHS: Fst=0.027, CDX: Fst=0.025) in the population study. In addition, we identified pairs of skin traits being at high risk of frequent co-occurrence (such as skin aging and wrinkles (r = 0.45, p =1.50e-5) or collagen degradation and moisturizing (r = 0.35, p = 1.1e-3). ConclusionThis is the first investigation in Vietnam to explore genetic variants of facial skin. These findings could improve inadequate skin-related genetic diversity in the currently published database.

bioinformatics↗

bioRxiv2023

Molecular Mechanisms Underlying Phenotypic Degeneration in Cordyceps militaris: Insights from Transcriptome Reanalysis and Osmotic Stress Studies

Phenotypic degeneration is a well-known phenomenon in fungi, yet the underlying mechanisms remain poorly understood. Cordyceps militaris, a valuable medicinal fungus with therapeutic potential and known bioactive compounds, is vulnerable to degeneration, which is a concern for producers. However, the causes of this process are still unclear. To shed light on the molecular mechanisms responsible for phenotypic degeneration in C. militaris, we isolated two strains with different abilities to form fruiting bodies. Our observations revealed that the degenerated strain had reduced ability to develop fruiting bodies, limited radial expansion, and increased spore density. We also conducted a transcriptome reanalysis and identified dysregulation of genes involved in the MAPK signaling pathway in the degenerate strain. Our RT-qPCR results showed lower expression of genes associated with sexual development and upregulation of genes linked to asexual sporulation in the degenerate strain compared to the wild-type strain. We also found dysregulation of genes involved in glycerol synthesis and MAPK regulation. Additionally, we discovered that osmotic stress reduced radial growth but increased conidia sporulation and glycerol accumulation in both strains, and hyperosmotic stress inhibited fruiting body formation in all neutralized strains. These findings suggest that the MAPK signaling pathway is dysregulated in the degenerate strain and the high-osmolarity glycerol and spore formation modules may be continuously activated, while the pheromone response and filamentous growth cascades may be downregulated. Overall, our study provides valuable insights into the mechanisms underlying C. militaris degeneration and identifies potential targets for future studies aimed at improving cultivation practices.

molecular biology↗

bioRxiv2017

Bacterial Community Shift in Marine Tar Balls following Low Salinity Exposure

The persistence and recurrence of tar balls causes detrimental effects on coastal wildlife, tourism, and fisheries. Previously, the human pathogen Vibrio vulnificus was detected in marine tar balls in the Gulf of Mexico. Marine tar balls also migrate to low-salt water bodies near the shore. The bacterial communities in tar balls from these environments, however, have not been fully characterized. Herein we describe our studies on the effect of reduced salinity on bacterial communities in marine tar balls. Tar balls collected from the Gulf of Mexico were incubated in deionized water for six months, and their microbial fingerprints were visualized using denaturing gradient gel electrophoresis. Our data show that the indigenous bacterial communities in marine tar balls shifted after being exposed to low-salinity condition. Dominant genera in the tar balls at low salinity were Aquisalimonas and Parvibaculum, neither of which includes known human pathogens.

ecology↗