Biology subjects

Pham, H. T.

Publications and source records attributed to Pham, H. T..

7 recordsLinked to original sources

bioRxiv2026

Detection of Pancreatic Cancer Using a Methylation-Specific PCR-Based Multi-Cancer Early Detection Test

ContextPancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy often diagnosed at advanced stages due to the lack of early clinical symptoms. DNA methylation alterations arise early in PDAC tumorigenesis and may serve as promising biomarkers for blood-based cancer detection. ObjectiveTo evaluate the performance of EPISEEK, a laboratory-developed blood-based multi-cancer early detection (MCED) assay, for detecting PDAC across disease stages. DesignA retrospective cohort study included 97 patients with stage I-IV PDAC and 201 asymptomatic healthy controls. Sensitivity, specificity, area under the curve (AUC), and stage-specific performance were assessed. EPISEEK-MCED performance was also compared with CA 19-9 alone and in combination with CA 19-9. ResultsEPISEEK-MCED classified 65 of 97 PDAC cases as positive, corresponding to an observed sensitivity of 70.1% (95% CI, 60.3% - 78.3%) at 99.5% specificity. The assay demonstrated strong discrimination between PDAC cases and healthy controls, with an AUC of 0.916 (95% CI, 0.88 - 0.952). Sensitivity increased with advancing stage while remaining substantial in early-stage disease, measuring 53.6% for stage I and 65.1% for stage II PDAC, 100% for stage III and 94.7% for stage IV. Across stages, EPISEEK-MCED outperformed CA 19-9 alone, particularly in early-stage disease. Combined analysis of EPISEEK-MCED and CA 19-9 further improved detection performance, achieving sensitivity of 57.1% and 81.4% for stage I and II, respectively. ConclusionsEPISEEK-MCED demonstrated high specificity and sensitivity for PDAC detection across disease stages, including early-stage disease. Combining EPISEEK-MCED with CA19-9 further improved performance, supporting its clinical utility for PDAC detection.

molecular biology↗

bioRxiv2026

GenPept-Curated-2025: A Benchmark Dataset for Antimicrobial Peptide Prediction with Homology-Controlled Partitioning

Antimicrobial peptides (AMPs) are promising therapeutic candidates against rising antimicrobial resistance, yet progress in AMP prediction is hampered by the lack of benchmark datasets that address homology leakage, negative set reliability, and distributional diversity. Existing AMP databases, designed as biological repositories, do not enforce the controlled partitioning required for rigorous machine learning evaluation. We present GenPept-Curated-2025, a curated, class-balanced benchmark of 11,000 peptide sequences (5,500 AMP / 5,500 non-AMP) derived from Bacteria, Archaea, and Fungi, and sourced exclusively from GenPept/NCBI Protein. The dataset was constructed through a reproducible pipeline comprising taxonomic scoping, quality control, precursor handling, annotation-based labeling, and Identical Protein Groups (IPG)-based deduplication, with sequence length restricted to 10-200 aa. The AMP proportion varies substantially across length bins (14.2% in [10, 50] aa to 77.1% in [101, 150] aa), identifying length-dependent class imbalance as a distribution shift that benchmarking must account for. The dataset is openly released to support standardized, reproducible, and leakage-free evaluation of AMP prediction models.

bioinformatics↗

bioRxiv2025

Siderophores can alter the population dynamics of fungal-bacterial communities by inhibiting specialized metabolism

Siderophores are microbial metabolites with a strong affinity for Fe(III) ions, in addition to other roles beyond iron acquisition. In this study, we propose that bacillibactin, a siderophore produced by the bacterium Bacillus subtilis, provides an advantage to its producer by inhibiting the specialized metabolism of antagonistic Penicillium fungi. Metabolome and transcriptome analyses indicate that iron deficiency caused by bacillibactin plays a critical role in downregulating the specialized metabolism of competing Penicillium species. Since many specialized metabolites of Penicillium spp. have antibacterial properties, we hypothesize that bacillibactin cross-protects other bacteria during fungal-bacterial community interactions. A tripartite coculture model demonstrated that bacillibactin production influences community dynamics by reducing the growth of specialized metabolite-producing Penicillium species, thereby facilitating the colonization of B. subtilis and other co-inhabiting bacterial species.

microbiology↗

bioRxiv2024

Interlaboratory comparison of standardised metabolomics and lipidomics analyses in human and rodent blood using the MxP(R) Quant 500 kit

Metabolomics and lipidomics are pivotal in understanding phenotypic variations beyond genomics. However, quantification and comparability of mass spectrometry (MS)-derived data are challenging. Standardised assays can enhance data comparability, enabling applications in multi-center epidemiological and clinical studies. Here we evaluated the performance and reproducibility of the MxP(R) Quant 500 kit across 14 laboratories. The kit allows quantification of 634 different metabolites from 26 compound classes using triple quadrupole MS. Each laboratory analysed twelve samples, including human plasma and serum, lipaemic plasma, NIST SRM 1950, and mouse and rat plasma, in triplicates. 505 out of the 634 metabolites were measurable above the limit of detection in all laboratories, while eight metabolites were undetectable in our study. Out of the 505 metabolites, 412 were observed in both human and rodent samples. Overall, the kit exhibited high reproducibility with a median coefficient of variation (CV) of 14.3 %. CVs in NIST SRM 1950 reference plasma were below 25 % and 10 % for 494 and 138 metabolites, respectively. To facilitate further inspection of reproducibility for any compound, we provide detailed results from the in-depth evaluation of reproducibility across concentration ranges using Deming regression. Interlaboratory reproducibility was similar across sample types, with some species-, matrix-, and phenotype-specific differences due to variations in concentration ranges. Comparisons with previous studies on the performance of MS-based kits (including the AbsoluteIDQ p180 and the Lipidyzer) revealed good concordance of reproducibility results and measured absolute concentrations in NIST SRM 1950 for most metabolites, making the MxP(R) Quant 500 kit a relevant tool to apply metabolomics and lipidomics in multi-center studies.

biochemistry↗

bioRxiv2022

Structural and molecular biology of Acheta domesticus segmented densovirus, the first parvovirus to harbor a bipartite genome

Parvoviruses (family Parvoviridae) are defined by their linear monopartite ssDNA genome, T=1 icosahedral capsid, and distinct structural (VP) and non-structural (NS) protein expression cassettes within their genome. Here, we report the first parvovirus with a segmented genome, Acheta domesticus segmented densovirus (AdSDV), a house cricket (Acheta domesticus) pathogen. The AdSDV harbors its NS and VP cassettes on two separate segmented genomes. Its VP segment acquired a phospholipase A2-encoding gene via inter-subfamily recombination, which is absent from its capsid. The AdSDV evolved a transcription profile in response to its multipartite replication strategy that has diverged from its Brevihamaparvovirus ancestors. Furthermore, AdSDV assembles three capsid populations, which package one genome segment per particle. The cryoEM structures of these three capsids (2.3 to 3.3 [A] resolution) reveal a genome packaging mechanism, which differs from other parvoviruses. This study provides a new perspective on ssDNA genome segmentation and on the plasticity of parvovirus biology.

microbiology↗

bioRxiv2021

Chemoproteomics Enabled Discovery of Selective Probes for NuA4 Factor BRD8

Bromodomain-containing proteins frequently reside in multisubunit chromatin complexes with tissue or cell state-specific compositions. Recent studies have revealed tumor-specific dependencies on the BAF complex bromodomain subunit BRD9 that are a result of recurrent mutations afflicting the structure and composition of associated complex members. To enable the study of ligand engaged complex assemblies, we established a chemoproteomics approach using a functionalized derivative of the BRD9 ligand BI-9564 as an affinity matrix. Unexpectedly, in addition to known interactions with BRD9 and associated BAF complex proteins, we identify a previously unreported interaction with members of the NuA4 complex through the bromodomain-containing subunit BRD8. We apply this finding, alongside homology model guided design, to develop chemical biology approaches for the study of BRD8 inhibition, and to arrive at first-in-class selective and cellularly active probes for BRD8. These tools will empower further pharmacological studies of BRD9 and BRD8 within respective BAF and NuA4 complexes.

biochemistry↗

bioRxiv2020

Single-chain lanthanide luminescence biosensors for cell-based imaging and screening of protein-protein interactions

Research tools that enable imaging or analysis of protein-protein interactions (PPIs) directly within living cells provide unique and valuable biological insights and can also aid drug discovery efforts. Here, we present lanthanide-based, Forster resonance energy transfer (lanthanide-based FRET, or LRET) biosensors for time-gated luminescence (TGL) imaging or multiwell plate analysis of PPIs. Polypeptide chains comprised of an alpha helical linker flanked by a Tb(III) complex, GFP and two binding domains exhibit large differences in long-lifetime, Tb(III)-to-GFP LRET-sensitized emission between open (unbound) and closed (bound) states. We used TGL microscopy to image ca. 500% increases in Tb(III)-to-GFP LRET following rapamycin addition to NIH 3T3 cells that expressed biosensors bearing FKBP12 and the rapamycin binding domain of m-Tor (FRB) at each terminus. Much larger signal changes, up to ca. 2500%, were observed when cells were grown in 96-well or 384-well plates and analyzed using a TGL plate reader. We also measured the interaction of p53 and HDM2 and its inhibition within intact HeLa cells grown in 96-well plates and estimated a z-factor of 0.5 for the assay. The modular design and high dynamic range of Tb(III)-based LRET biosensors will facilitate versatile imaging and cell-based screening of PPIs.

biochemistry↗