Biology subjects

Phan, H.

Publications and source records attributed to Phan, H..

10 recordsLinked to original sources

bioRxiv2026

A data model for longitudinal multi-modal biomedical cohorts

Longitudinal multimodal cohort studies require data models that can integrate heterogeneous molecular, phenotypic, and contextual data while preserving relationships across participants, biospecimens, study visits, and computational transformations. Here, we present the data model developed for the Multi-Omics for Health and Disease (MOHD) Consortium, a modality-agnostic, provenance-driven framework designed to support an evolving longitudinal biomedical resource. The model uses a compact set of linked entities and a central dataset abstraction to represent experimental, phenotypic and contextual, and computational data within a common framework. Stable identifiers, explicit provenance relationships, and flexible grouping structures enable data to be tracked across biological sources, processing workflows, and releases without requiring modality-specific restructuring of the core model. To address the complexity of participant context, we developed a harmonization framework that transforms branched REDCap survey data into a longitudinal, machine-readable representation with normalized variables and explicit response status. Interoperability with external data models and ontologies is supported through reproducible translation workflows while maintaining a stable canonical representation. We demonstrate the model through its implementation in the first production-scale MOHD data release, encompassing 956 participants, nearly 7,000 datasets, and more than 40,000 files across multiple molecular modalities and study visits. This implementation demonstrates the ability of the model to accommodate heterogeneous and longitudinal data, evolving computational products, participant withdrawal, and distinct data-access environments. Together, the MOHD implementation provides a practical framework and generalizable design principles for building longitudinal multimodal biomedical resources that remain traceable, interoperable, and adaptable as data and analytical requirements evolve.

bioinformatics↗

bioRxiv2025

Evidence of a distinct Blumeria graminis f. sp. tritici pathotype structure in Australian wheat powdery mildew: implications for resistance breeding.

The obligate biotrophic fungus Blumeria graminis f. sp. tritici (Bgt) is the causal agent of wheat powdery mildew. To investigate virulence diversity, 30 Australian Bgt isolates collected between 2020 and 2024 were screened against a panel of 24 wheat lines carrying defined resistance (R) genes. Pathotyping analysis indicated that the Australian Bgt population is diverse in its virulence profile. Non-metric multidimensional scaling analysis of disease phenotyping revealed evidence of six distinct Bgt pathotype groups. In addition, we identified wheat varieties carrying defined R genes and their combinations that remain effective against the contemporary Australian Bgt. Notably, wheat cvs Khapli and Tabasco, possessing Pm4a and Pm2, respectively, in addition to unknown R gene(s), were highly resistant to all the isolates tested. Furthermore, elite European varieties that possess durable resistance, such as Alchemy and Cordiale, display complete to moderate resistance against all selected isolates representing the Australian pathotype groups.

microbiology↗

bioRxiv2025

PathogenSurveillance: an automated pipeline for population genomic analyses and pathogen identification

Whole genome sequencing (WGS) offers a comprehensive, organism-agnostic method that effectively meets the need for efficient, reliable, and standardized responses to emerging threats from pathogens and pests. Here, we present PathogenSurveillance, an open-source and automated Nextflow pipeline for population genomic analyses of WGS data. It is designed with features tailored for biosurveillance and is suitable for in-field or point-of-care diagnostics. PathogenSurveillance is flexible, accommodating short- and long-read datasets and mixed samples of prokaryotes and/or eukaryotes. It automates all steps, including reference identification and retrieval from the NCBI Assembly database, and produces customizable interactive reports with summaries, phylogenetic trees, and minimum spanning networks that enable species and subspecies level identification. It also outputs quality control metrics and carefully names and organizes output files to facilitate downstream analyses. The pipeline runs on any Linux-based system and minimizes the need for advanced computational expertise. Source code is available on GitHub under the open-source MIT license. The pipeline expands the toolkit for real-time biosurveillance, enabling rapid detection and monitoring of pathogens and pests for rapid response to novel variants.

bioinformatics↗

bioRxiv2024

Residual Partial Least Squares Learning: Brain Cortical Thickness Simultaneously Predicts Eight Non-pairwise-correlated Behavioural and Disease Outcomes in Alzheimer's Disease

Alzheimers Disease (AD) is the leading cause of dementia, affecting brain structure, function, cognition, and behaviour. While previous studies have linked brain regions to univariate outcomes (e.g., disease status), the relationship between brain-wide changes and multiple disease and behavioural outcomes of AD is still not well understood. Here, we propose Residual Partial Least Squares (re-PLS) Learning, an explainable and generalisable framework that models high-dimensional brain features and multivariate outcomes, accounting for confounders. Using re-PLS, we map the many-to-many pathways between cortical thickness and multivariate AD outcomes; identify neural biomarkers that simultaneously predict multiple outcomes; control for confounding variables; conduct longitudinal AD prediction; and perform cross-cohort AD prediction. To evaluate its efficacy, we first carry out within-cohort cross-subject validation using ADNI data, and further examine its reproducibility via between-cohort cross-validation using ADNI and OASIS data. Together, our results unveil brain regions jointly but differentially predictive of distinctive cognitive-behavioural scores in AD.

neuroscience↗

bioRxiv2023

Exercise Mitigates Flow Recirculation and Activates Mechanosensitive Transcriptome to Uncover Endothelial SCD1-Catalyzed Anti-Inflammatory Metabolites

Exercise modulates vascular plasticity in multiple organ systems; however, the metabolomic transducers underlying exercise and vascular protection in the disturbed flow-prone vasculature remain under-investigated. We simulated exercise-augmented pulsatile shear stress (PSS) to mitigate flow recirculation in the lesser curvature of the aortic arch. When human aortic endothelial cells (HAECs) were subjected to PSS ({tau}ave = 50 dyne{middle dot}cm-2, {partial}{tau}/{partial}t = 71 dyne{middle dot}cm-2{middle dot}s-1, 1 Hz), untargeted metabolomic analysis revealed that Stearoyl-CoA Desaturase (SCD1) in the endoplasmic reticulum (ER) catalyzed the fatty acid metabolite, oleic acid (OA), to mitigate inflammatory mediators. Following 24 hours of exercise, wild-type C57BL/6J mice developed elevated SCD1-catalyzed lipid metabolites in the plasma, including OA and palmitoleic acid (PA). Exercise over a 2-week period increased endothelial SCD1 in the ER. Exercise further modulated the time-averaged wall shear stress (TAWSS or{tau} ave) and oscillatory shear index (OSIave), upregulated Scd1 and attenuated VCAM1 expression in the disturbed flow-prone aortic arch in Ldlr-/- mice on high-fat diet but not in Ldlr-/-Scd1EC-/- mice. Scd1 overexpression via recombinant adenovirus also mitigated ER stress. Single cell transcriptomic analysis of the mouse aorta revealed interconnection of Scd1 with mechanosensitive genes, namely Irs2, Acox1 and Adipor2 that modulate lipid metabolism pathways. Taken together, exercise modulates PSS ({tau}ave and OSIave) to activate SCD1 as a metabolomic transducer to ameliorate inflammation in the disturbed flow-prone vasculature.

physiology↗

bioRxiv2022

Sensing Echoes: Temporal misalignment as the Earliest Marker of Neurodevelopmental Derail

Neurodevelopmental disorders are on the rise worldwide, with diagnoses that detect derailment from typical milestones by 3-4.5 years of age. By then, the circuitry in the brain has already reached some level of maturation that inevitably takes neurodevelopment through a different course. There is a critical need then to develop analytical methods that detect problems much earlier and identify targets for treatment. We integrate data from multiple sources, including neonatal auditory brainstem responses (ABR), clinical criteria detecting autism years later in those neonates, and similar ABR information for young infants and children who also received a diagnosis of autism spectrum disorders, to produce the earliest known digital screening biomarker to flag neurodevelopmental derailment in neonates. This work also defines concrete targets for treatment and offers a new statistical approach to aid in guiding a personalized course of maturation in line with the highly nonlinear, accelerated neurodevelopmental rates of change in early infancy. Significance StatementAutism is currently detected on average after 4.5 years of age, based on differences in social interactions. Yet basic building blocks that develop to scaffold social interactions are present at birth and quantifiable at clinics. Auditory Brainstem Response tests, routinely given to neonates, infants, and young children, contain information about delays in signal transmission important for sensory integration. Although currently discarded as gross data under traditional statistical approaches, new analytics reveal unambiguous differences in ABR signals fluctuations between typically developing neonates and those who received an autism diagnosis. With very little effort and cost, these new analytics could be added to the clinical routine testing of neonates to create a universal screening tool for neurodevelopmental derailment and prodrome of autism.

neuroscience↗

bioRxiv2021

A two-component protein condensate of EGFR and Grb2 regulates Ras activation at the membrane

We reconstitute a phosphotyrosine-mediated protein condensation phase transition of the [~]200 residue cytoplasmic tail of the epidermal growth factor receptor (EGFR) and the adaptor protein, Grb2, on a membrane surface. The phase transition depends on phosphorylation of the EGFR tail, which recruits Grb2, and the dimerization of Grb2, which provides the crosslinking element for condensation with EGFR. The Grb2 Y160 residue plays a structurally critical role in dimer formation, and phosphorylation or mutation of Y160 prevents EGFR:Grb2 condensation. By extending the reconstitution experiment to include the guanine nucleotide exchange factor, SOS, and its substrate Ras, we further find that EGFR condensation controls the ability of SOS to activate Ras. These results identify an EGFR:Grb2 protein condensation phase transition as a regulator of signal propagation from EGFR to the MAPK pathway.

biophysics↗

bioRxiv2021

Variability in an effector gene promoter of a necrotrophic fungal pathogen dictates epistasis and effector-triggered susceptibility in wheat

The fungus Parastagonospora nodorum uses proteinaceous necrotrophic effectors (NEs) to induce tissue necrosis on wheat leaves during infection, leading to the symptoms of septoria nodorum blotch (SNB). The NEs Tox1 and Tox3 induce necrosis on wheat possessing the dominant susceptibility genes Snn1 and Snn3B1/Snn3D1, respectively. We previously observed that Tox1 is epistatic to the expression of Tox3 and a quantitative trait locus (QTL) on chromosome 2A that contributes to SNB resistance/susceptibility. The expression of Tox1 is significantly higher in the Australian strain SN15 compared to the American strain SN4. Inspection of the Tox1 promoter region revealed a 401 bp promoter genetic element in SN4 positioned 267 bp upstream of the start codon that is absent in SN15, called PE401. Analysis of the world-wide P. nodorum population revealed that a high proportion of Northern Hemisphere isolates possess PE401 whereas the opposite was observed in the Southern Hemisphere. The presence of PE401 ablates the epistatic effect of Tox1 on the contribution of the SNB 2A QTL but not Tox3. PE401 was introduced into the Tox1 promoter regulatory region in SN15 to test for direct regulatory roles. Tox1 expression was markedly reduced in the presence of PE401. This suggests a repressor molecule(s) binds PE401 and inhibits Tox1 transcription. Infection assays also demonstrated that P. nodorum which lacks PE401 is more pathogenic on Snn1 wheat varieties than P. nodorum carrying PE401. An infection competition assay between P. nodorum isogenic strains with and without PE401 indicated that the higher Tox1-expressing strain rescued the reduced virulence of the lower Tox1-expressing strain on Snn1 wheat. Our study demonstrated that Tox1 exhibits both selfish and altruistic characteristics. This offers an insight into a NE arms race that is occurring within the P. nodorum population. The importance of PE401 in breeding for SNB resistance in wheat is discussed. Author summaryBreeding for durable resistance to fungal diseases in crops is a continual challenge for crop breeders. Fungal pathogens evolve ways to overcome host resistance by masking themselves through effector evolution and evasion of broad-spectrum defense responses. Association studies on mapping populations infected by isolate mixtures are often used by researchers to seek out novel sources of genetic resistance. Disease resistance quantitative trait loci (QTL) are often minor or inconsistent across environments. This is a particular problem with septoria diseases of cereals such as septoria nodorum blotch (SNB) of wheat caused by Parastagonospora nodorum. The fungus uses a suite of necrotrophic effectors (NEs) to cause SNB. We characterised a genetic element, called PE401, in the promoter of the major NE gene Tox1, which is present in some P. nodorum isolates. PE401 functions as a transcriptional repressor of Tox1 and exerts epistatic control on another major SNB resistance QTL in the host. In the context of crop protection, constant surveillance of the pathogen population for the frequency of PE401 in conjunction with NE diversity will enable agronomists to provide the best advice to growers on which wheat varieties can be tailored to provide optimal SNB resistance to regional pathogen population genotypes.

microbiology↗

bioRxiv2021

A palmitoylation code controls PI4KIIIα complex formation and PI(4,5)P2 homeostasis at the plasma membrane

PI4KIII is the major enzyme responsible for generating the phosphoinositide PI(4)P at the plasma membrane. This lipid kinase forms two multicomponent complexes, both including a palmitoylated anchor, EFR3. Whereas both PI4KIII complexes support production of PI(4)P, the distinct functions of each complex and mechanisms underlying the interplay between them remain unknown. Here, we present roles for differential palmitoylation patterns within a tri-Cys motif in EFR3B (Cys5/Cys7/Cys8) in controlling the distribution of PI4KIII between these two complexes at the plasma membrane and corresponding functions in phosphoinositide homeostasis. Spacing of palmitoyl groups within three doubly palmitoylated EFR3B "lipoforms" affects both its interactions with TMEM150A, a transmembrane protein governing formation of a PI4KIII complex functioning in rapid PI(4,5)P2 resynthesis following PLC signaling, and its partitioning within liquid-ordered and -disordered regions of the plasma membrane. This work identifies a palmitoylation code in controlling protein-protein and protein-lipid interactions affecting a plasma membrane-resident lipid biosynthetic pathway. SUMMARY STATEMENTDifferent palmitoylation patterns on a lipid kinase adaptor protein control partitioning of the kinase between two spatiotemporally and functionally distinct complexes within the plasma membrane.

cell biology↗

bioRxiv2020

Identifying Neural Signatures Mediating Behavioral Symptoms and Psychosis Onset: High-Dimensional Whole Brain Functional Mediation Analysis

Along the pathway from behavioral symptoms to the development of psychotic disorders sits the multivariate mediating brain. The functional organization and structural topography of large-scale neural mediators among patients with brain disorders, however, are not well understood. Here, we design a high-dimensional brain-wide functional mediation framework to investigate brain regions that intermediate between baseline behavioral symptoms and future conversion to full psychosis among individuals at clinical high risk (CHR). Using resting-state functional magnetic resonance imaging (fMRI) data from 263 CHR subjects, we extract an brain atlas and a {beta} brain atlas: the former underlines brain areas associated with prodromal symptoms and the latter highlights brain areas associated with disease onset. In parallel, we identify the P mediators and the N mediators that respectively facilitate or protect against developing brain disorders among subjects with more severe behavioral symptoms and quantify the effect of each neural mediator on disease development. Taken together, the -{beta} atlases and the P-N mediators paint a brain-wide picture of neural markers that are potentially regulating behavioral symptoms and the development of psychotic disorders and highlight a statistical framework that is useful to uncover large-scale intermediating variables in a regulatory biological organization.

bioinformatics↗