Biology subjects

Nguyen, H. V.

Publications and source records attributed to Nguyen, H. V..

11 recordsLinked to original sources

bioRxiv2026

CodeCytos: AI-assisted spatial molecular imaging analysis via code-augmented agent action space

Conventional tissue image analysis software provides foundational capabilities for cellular analysis, including segmentation, basic morphological feature extraction, and spatial organization analysis. However, these tools often require manual intervention and are not well integrated with code-driven automation, limiting efficiency and scalability for complex spatial tissue studies. In addition, they offer limited flexibility for custom analyses, as they typically support only a fixed set of pre-implemented spatial cellular features. To address these limitations, we propose CodeCytos, a coding-based reasoning agent framework that enables dynamic, programmable interaction with spatial molecular imaging data, to improve automation and customization. CodeCytos is designed to streamline the exploration of custom spatial cellular features and adapt to diverse research needs. We demonstrate its utility through case studies on four expert-curated datasets from distinct tissue types: frontal cortex, non-small-cell lung cancer, pancreas, and tonsil. We evaluate CodeCytos under a realistic minimal prompt setting, where bioscientists pose simple questions without task-specific instructions or contextual information about spatial cellular analysis, and benchmark multiple LLM backbones with strong coding capabilities. We further show that incorporating tailored, domain-agnostic few-shot in-context coding-reasoning examples (randomly sampled demonstrations outside the spatial analysis domain) can substantially improve performance without requiring costly, expert-crafted in-domain demonstrations. Overall, CodeCytos outperforms baseline approaches, highlighting the potential of code-action agents to assist with custom feature exploration in spatial molecular imaging and to accelerate biomarker discovery.

bioinformatics↗

bioRxiv2026

HDAC Inhibition Sensitizes Pancreatic Tumors to DNA Damage by Global Redistribution of the Transcriptional Machinery

The DNA damage response (DDR) is critical for pancreatic ductal adenocarcinoma (PDAC) development and therapeutic responses, including to genotoxic agents. While epigenetic modulators have been shown to contribute to the DDR, how chromatin regulation dictates responses to DNA damage in PDAC remains incompletely understood. Here, we identify Class I histone deacetylases (HDACs) as critical regulators of the DDR. HDAC1/2 directs the genomic distribution of H3K27ac, ensuring sufficient BRD4 and RNA polymerase II (Pol II) occupancy at DDR gene promoters. HDAC inhibition by entinostat shifts the balance of H3K27 acetylation preferentially towards intergenic regions, diverting BRD4 and Pol II from promoters, thereby suppressing DDR gene expression. In line with this, HDAC inhibition heightens DNA damage and sensitizes PDAC to diverse DNA-damaging and DDR-targeting agents. Since the clinical development of HDAC inhibitors has been limited by systemic toxicity, we developed bottlebrush prodrug (BPD) nanoparticles for tumor-selective entinostat delivery. Entinostat-BPD achieved tumor-specific HDAC inhibition while displaying potent efficacy and reduced systemic toxicity. These findings reveal an HDAC-dependent DDR vulnerability and offer combinational and precision targeting strategies to facilitate clinical translation and improve PDAC patient outcomes. SIGNIFICANCE STATEMENTThe ability of tumor cells to tolerate DNA damage limits the efficacy of many anticancer therapies. Our study reveals that pancreatic cancer cells enforce this resistance by sustaining expression of DNA damage response (DDR) genes through Class I histone deacetylases (HDACs). HDACs maintain genome-wide acetylation patterns required for efficient recruitment of the transcriptional machinery to DDR genes. Pharmacological HDAC inhibition disrupts this process and sensitizes pancreatic cancer cells to diverse DNA-damaging agents. To overcome systemic toxicity that limits translational potential, we further establish a bottlebrush prodrug nanoparticle platform that enables tumor-selective HDAC inhibition. Given the central role of the DDR in cancer, targeting HDAC-mediated DDR regulation through drug combinations and precision delivery may have broad therapeutic relevance across cancer types.

cancer biology↗

bioRxiv2026

MNT loss in MYC-driven B lymphoma cells enhances apoptosis, inhibits proliferation and increases sensitivity to cancer drugs.

Our previous mouse genetic studies showed that loss of the transcription repressor MNT enhanced apoptosis of premalignant lymphoid cells over-expressing MYC and inhibited lymphoma development. Here, we have explored the consequences of inducing Mnt deletion in fully malignant lymphoma cells. MNT loss provoked apoptosis of p53 wt and, albeit more slowly, p53 mutant E-Myc lymphoma cells, preceded by elevated levels of major BH3-only proteins BIM and PUMA. By inhibiting apoptosis, we showed that MNT loss also impaired cell cycling and increased senescence. E-Myc lymphoma cells depend on the BCL-2 ortholog MCL-1 for survival and expansion and, importantly, MNT loss enhanced their sensitivity to the MCL-1 inhibitor S63845 and to several chemotherapeutic agents. In BCL-2-overexpressing E-Myc lymphoma cells, which model aggressive human Double Hit Lymphomas, MNT loss enhanced sensitivity to the BCL-2 inhibitor ABT-199, even after BAX loss. Furthermore, MNT deletion improved drug responses of two long-established Burkitt Lymphoma cell lines. SIGNIFICANCEThis study establishing the MNT dependency of E-Myc lymphoma cells and demonstrating that MNT loss enhances their sensitivity to apoptosis induced by conventional chemotherapeutics and BH3 mimetic drugs provides strong proof-of-concept for developing MNT inhibitors to improve treatment of MYC-driven blood cancers.

cancer biology↗

bioRxiv2026

Spatially Anchored Regulatory State Inference in Melanoma

Spatial transcriptomics (ST) captures gene expression within tissue architecture but lacks direct regulatory information, while single-cell multiome assays profile transcriptional and chromatin states without spatial context. We present a framework for spatially anchored regulatory inference that integrates Visium ST with single-cell multiome data to infer spatially resolved regulatory programs. Building upon GraphST, we introduce spatially regularized cell-to-spot mapping and propagate chromatin accessibility and transcription factor motif activity into tissue space. Regulatory analysis is performed at the spatial domain level via joint differential expression and accessibility testing, along with quantitative concordance assessment. Applied to melanoma tissue sections, the framework reveals spatially localized regulatory programs and shows that assignment strategy substantially affects downstream regulatory stability. This modular approach enables interpretable gene-, peak-, and transcription factor-level outputs for multimodal spatial analysis.

bioinformatics↗

bioRxiv2024

The Multifunctional Catalytic Hemoglobin from Amphitrite ornata: Protocols on Isolation, Taxonomic Identification, Protein Extraction, Purification, and Characterization

The multifunctional catalytic hemoglobin from the terebellid polychaete Amphitrite ornata, also named dehaloperoxidase (AoDHP), utilizes the typical oxygen transport function in addition to four observed activities involved in substrate oxidation. The multifunctional ability of AoDHP is presently a rare observation, and there exists a limitation for how novel dehaloperoxidases can be identified from macrobenthic infauna. In order to discover more infaunal DHP-bearing candidates, we have devised a facilitated method for an accurate taxonomic identification that places visual and molecular taxonomic approaches in parallel. Traditional visual taxonomic species identification by the non-specialist, at least for A. ornata, or even for other marine worms, is a very difficult and time-consuming task since a large diversity is present and the method is restricted to adult worm specimens. The work herein aimed to describe a method that particularly simplifies the taxonomic identification of A. ornata through the assessment of its mitochondrial cytochrome c oxidase subunit I gene by employing the DNA barcoding technique. Furthermore, whole worm specimens of A. ornata were used to extract and purify AoDHP followed by an H2O2-dependent peroxidase activity assay evaluation against substrate 2,4,6-trichlorophenol. AoDHP isoenzyme A was also overexpressed as the recombinant protein in Escherichia coli, and its peroxidase activity parameters were compared to AoDHP from the natural source. The activity assay assessment indicated a tight correlation for all Michaelis-Menten parameters evaluated. We conclude that the method described herein exhibits a streamlined approach to identify the polychaete A. ornata, which can be adopted by the non-specialist, and the full procedure is predicted to facilitate the discovery of novel dehaloperoxidases from other marine invertebrates.

biochemistry↗

bioRxiv2023

An Efficient Computational Method to Create Positive NIPT Samples with Autosomal Trisomy

Noninvasive prenatal test (NIPT) has been widely used for screening trisomy on chromosomes 13 (T13), 18 (T18), and 21 (T21). However, the false negative rate of NIPT algorithms has not been thoroughly evaluated due to the lack of positive samples. In this study, we present an efficient computational approach to create positive samples with autosomal trisomy from negative samples. We applied the approach to establish a low coverage dataset of 1440 positive samples with T13, T18, and T21 aberrations for both mosaic and non-mosaic conditions. We examined the performance of WisecondorX and its improvement, called VINIPT, on both negative and positive datasets. Experiments showed that WisecondorX and VINIPT with a z-score threshold of 3.3 were able to detect all non-mosaic samples with T13, T18, and T21 aberrations (i.e., the sensitivity of 100%). Using a lower z-score threshold of 2.58 when analyzing mosaic samples, both WisecondorX and VINIPT have the overall sensitivity of 99.7% on detecting T13, T18, and T21 aberrations from mosaic samples. WisecondorX has the specificity of 98.5% for the non-mosaic analysis, but a considerably lower specificity of 95% for the mosaic analysis. VINIPT has a much better specificity than WisecondorX, i.e., 99.9% for the non-mosaic analysis, and 98.2% for the mosaic analysis. The results suggest that VINIPT can play as a powerful NIPT tool for the low coverage data.

bioinformatics↗

bioRxiv2023

Video Diffusion models for the apoptosis forcasting

Reliable and early prediction of cell death (apoptosis) is critically important in various areas of biology, particularly in characterizing the effectiveness of cell-based infusion products utilized for cancer immunotherapy. While deep Convolutional Neural Networks (CNNs) are often used in state-of-the-art approaches for apoptosis classification, they typically focus solely on individual cells and ignore cell-cell interaction. To address this limitation, we propose a novel generative approach based on a video diffusion model, which predicts future cellular behaviors for early detection of apoptosis events, even before molecular markers like Annexin-V or visual indications like membrane blebbing become apparent. Our approach accounts for the interactions of multiple target cells and their spatial and temporal relationships at each time frame. We condition our generative model on two starting frames and utilize an auto-regressive framework to predict the subsequent five frames. Our model achieves a 0.88 F1 score on the cell death event classification and 2.11 mean absolute death-time error, significantly outperforming state-of-the-art methods.

cell biology↗

bioRxiv2023

Nuclear localization of HD-Zip IV transcription factor GLABRA2 is driven byImportin α

GLABRA2 (GL2), a class IV homeodomain leucine-zipper (HD-Zip IV) transcription factor (TF) from Arabidopsis, is a developmental regulator of specialized cell types in the epidermis. GL2 contains a putative monopartite nuclear localization sequence (NLS) partially overlapping with its homeodomain (HD). We demonstrate that NLS deletion or alanine substitution of its basic residues (KRKRKK) affects nuclear localization and results in a loss-of-function phenotype. Fusion of the predicted NLS (GTNKRKRKKYHRH) to the fluorescent protein EYFP is sufficient for its nuclear localization in roots and trichomes. The functional NLS is evolutionarily conserved in a distinct subset of HD-Zip IV members including PROTODERMAL FACTOR2 (PDF2). Despite partial overlap of the NLS with the HD, genetic dissection of the NLS from PDF2 indicates that nuclear localization and DNA binding are separable functions. Affinity purification of GL2 from plant tissues followed by mass spectrometry-based proteomics identified Importin (IMP) isoforms as potential GL2 interactors. NLS structural prediction and molecular docking studies with IMP-3 revealed major interacting residues. Split-ubiquitin cytosolic yeast two-hybrid assays suggest interaction between GL2 and four IMP isoforms from Arabidopsis. Direct interactions were verified in vitro by co-immunoprecipitation with recombinant proteins. IMP triple mutants (imp- 1,2,3) exhibit defects in EYFP:GL2 nuclear localization in trichomes but not in roots, consistent with tissue-specific and redundant functions of IMP isoforms in Arabidopsis. Taken together, our findings provide mechanistic evidence for IMP-dependent nuclear localization of GL2 and other HD-Zip IV TFs in plants. One sentence summaryGLABRA2, a representative HD-Zip IV transcription factor from Arabidopsis, contains an evolutionarily conserved monopartite nuclear localization sequence that is recognized by Importin for translocation to the nucleus, a process that is necessary for cell-type differentiation of the epidermis.

plant biology↗

bioRxiv2023

A Novel Subtype of Myeloproliferative Neoplasms Driven by a MYC-Alarmin Axis

Despite advances in understanding the genetic abnormalities in myeloproliferative neoplasms (MPNs) and the development of JAK2 inhibitors, there is an urgent need to devise new treatment strategies, particularly for triple negative myelofibrosis (MF) patients whose MPNs lack mutations in the JAK2 kinase pathway and have very poor clinical outcomes. Here we report that MYC copy number gain and increased MYC expression frequently occur in triple negative MF, and that MYC-directed activation of S100A9, an alarmin protein that plays pivotal roles in inflammation and innate immunity, is necessary and sufficient to drive development and progression of MF. Notably, the MYC-S100A9 circuit provokes a complex network of inflammatory signaling that involves various hematopoietic cell types in the bone marrow microenvironment. Accordingly, genetic ablation of S100A9 or treatment with small molecules targeting the MYC-S100A9 pathway effectively ameliorates MF phenotypes, highlighting the MYC-alarmin axis as a novel therapeutic vulnerability for this subgroup of MPNs. SIGNIFICANCEThis study establishes that MYC expression is increased in triple negative MPNs via trisomy 8, that a MYC-S100A9 circuit manifest in these cases is sufficient to provoke myelofibrosis and inflammation in diverse hematopoietic cell types in the BM niche, and that the MYC-S100A9 circuit is targetable in triple negative MPN.

cancer biology↗

bioRxiv2020

Discovery of new genetic determinants controlling the morphological plasticity in rice root and shoot under phosphate starvation using GWAS

Phosphorus is an essential nutrient for plants that is often in short supply. In rice (Oryza sativa L.), phosphate (Pi) deficiency leads to various physiological disorders that consequently affect plant productivity. In this study, a large-scale phenotyping experiment of a set of 160 Vietnamese rice landraces was performed under greenhouse conditions by employing an alpha lattice design with three replicates to identify quantitative trait loci (QTLs) associated with plant growth inhibition by Pi deficiency. Rice plantlets were grown for six weeks in the PVC sand column (16 cm diameter x 80 cm height) supplied with Pi-deficient (10 {micro}M P) medium or full Pi Yoshida (320 {micro}M P) medium. The effects of Pi deficiency on the number of crown roots, root length, shoot length, root weight, shoot weight and total weight were studied. From 36 significant markers identified by using Genome-wide association study, a total of 21 QTLs associated with plant growth inhibition under Pi starvation conditions were defined. A list of 158 candidate genes co-located with defined QTLs was found. Interestingly, a QTL namely qRST9.14 were detected found common across three weight-traits. The co-located gene GLYCEROPHOSPHODIESTER PHOSPHODIESTERASE 13 was found potentially involved in Pi transport. Understanding the molecular mechanisms of Pi starvation responses, and identifying potential QTLs responsible for low-Pi stress tolerance will provide valuable information for developing new varieties tolerant to low-Pi conditions.

plant biology↗

bioRxiv2020

Development of a Synthetic Poxvirus-Based SARS-CoV-2 Vaccine

Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we used this novel vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a novel vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.Competing Interest StatementThe authors have declared no competing interest.View Full Text

immunology↗