Biology subjects

Lin, A. Y.

Publications and source records attributed to Lin, A. Y..

8 recordsLinked to original sources

bioRxiv2025

VO: The Vaccine Ontology

With the widespread use of vaccines in research and clinical settings, there is an urgent need to standardize vaccine representation, integrate information across diverse vaccine types, and support computer-assisted reasoning. Accordingly, we have since 2007 developed the community-based Vaccine Ontology (VO), which aligns with the Basic Formal Ontology and adheres to OBO Foundry principles. VO models ontologically vaccines, vaccine components, vaccine immune responses, vaccine investigation studies and other vaccine-related topics. VO represents more than 10,000 vaccines targeting 289 infectious pathogens and cancers in humans and over 30 nonhuman animal species. VO provides mappings to external resources such as RxNorm, CVX, FDA, and USDA. Various VO use cases exist. VO facilitates vaccine standardization in resources such as the VIOLIN vaccine database, ImmPort, and the Vaccine Adjuvant Compendium (VAC). Semantic queries can be made to query VO. VO has been shown to enhance experimental and clinical vaccine data analysis and vaccine literature mining. Overall, VO standardizes vaccine modeling and representation and greatly supports vaccine AI research in the Semantic Web era.

bioinformatics↗

bioRxiv2025

Immune Biomarkers, Profiles, and Responses: A Vaccine Ontology Perspective

BackgroundVaccines have the ability to induce a range of immune responses under different conditions, for example stimulating the production of neutralizing antibodies to block pathogen entry or activating cytotoxic T-cells to eliminate infected cells. Many such immune responses have not been thoroughly examined and classified. The Vaccine Ontology (VO) is a community-based ontology in the domain of vaccinology. We here describe how VO is used to represent the variety of immune responses associated with vaccines, together with associated biomarkers and profiles. ResultsThe VO differentiates vaccination and vaccine immunization. The former is a process of administering a vaccine in vivo; the latter is the outcome of vaccine induction of immune response. This distinction is critical for understanding both the procedure of vaccination and the resulting immune effects. VO also models and represents various vaccine-induced responses at multiple biological levels, including population, organism, organ/tissue, cell, and gene/protein levels. Such an approach captures the complexity of vaccine-induced immunity, from population-wide trend (for example: herd immunity) to molecular mechanisms. VO defines immune biomarkers as material entities such as neutralizing antibodies that signify humoral immune response, and IFN-gamma that is indicative of cell-mediated responses. Such biomarkers provide measurable indicators of the immune systems functional state post vaccination, enabling robust evaluation of vaccine efficacy. VO classifies immune response profile and correlated profile (or correlate) of immune protection as process profiles, a class in the Basic Formal Ontology (BFO 2.0). Immune response profiles, such as Th1 (or Th2)- biased profile, can be induced by various vaccines and vaccine adjuvants. Different types of correlated profile of immune protection are also identified, such as mechanistic and non-mechanistic correlates of immune protection. Such distinctions help us to quickly identify biomarkers and associated prediction and measurement of different kinds of vaccine protection. ConclusionThe important immune-related terms for immune biomarkers, profiles, and responses are modeled ontologically in VO together with their interrelations. The results support enhanced classification and analysis of vaccine-induced immune responses and related biomarkers and immune profiles, leading to further understanding of the vaccine immune mechanisms and enhanced vaccine research and development.

immunology↗

bioRxiv2025

Mapping and Harmonization of CVX vaccine terms tothe Vaccine Ontology

BackgroundWith many vaccines developed and used, it is critical to standardize vaccine information. The OHDSI OMOP Common Data Model (CDM), widely used to support EHR data integration and analysis, leverages CVX, RxNorm, and RxNorm Extension codes to standardize vaccine-related records. However, these terminologies lack robust semantic relations, making the vaccine classification ineffective in OMOP CDM. To address this issue, our OHDSI Vaccine Vocabulary Working Group proposes to use the Vaccine Ontology (VO) to map these standards and build up its own semantic relations. As a first study of the work, we performed the mapping and alignment of the Vaccine Administered (CVX) codes with the VO using a combination of semi-automatic and manual mapping methods. ResultsA total of 273 CVX terms were first collected and classified. A high-level VO design pattern and an exact one-to-one mapping strategy were developed to guide the CVX-to-VO term mapping. To facilitate the manual mapping and harmonization process, we also developed and evaluated three semi-automated mapping approaches utilizing lexical and semantic information of vaccine concepts to map CVX to VO. These approaches suggested candidate VO mappings for CVX terms and also indicated CVX terms that were unmappable to VO and required new term additions to VO. The application of the best approach to the 2022-10-05 release of VO achieved an accuracy of 85.55% for its suggestions. The suggestions made by the semi-automated approaches were taken into account to further enhance the mappings, which led to our eventual mapping of all CVX terms to the latest version of VO. We innovatively proposed the inclusion of the passive vaccine branch in VO, which includes 24 immunoglobulins and antitoxins from CVX as passive vaccines. A specific CVX-VO OWL file was developed and added to the VO GitHub. Use case queries were developed to demonstrate its support for computer-assisted queries of vaccine groups based on CVX-VO hierarchies. ConclusionAll CVX terms were mapped to the VO using our combined semi-automatic and manual mapping methods. The mapped results enhanced semantic vaccine classification, providing a basis for further OMOP vaccine classification and EHR data analysis.

bioinformatics↗

bioRxiv2024

Physiologic Regulation of Lipid Oxidation and Ferroptosis By Vitamin E, High-Density Lipoprotein, and Scavenger Receptor Class B Type 1

Ferroptosis is a form of cell death caused by oxidative (-OOH) damage to phospholipids (PL) that comprise the cell membrane. Understanding mechanisms of ferroptosis is important because of the role it plays in human disease, including cancer and neurodegeneration. Previous work has focused on the intracellular antioxidant enzyme glutathione peroxidase 4 (GPx4), which detoxifies PL-peroxides (PL-OOH) and prevents ferroptosis. Studies also show that alpha-tocopherol (-toc), the active form of Vitamin E, is an exogenous lipophilic antioxidant that inhibits ferroptosis in cancer cells in vitro and in neurons and hematopoietic stem cells in vivo. The mechanisms by which -toc engages cells to manipulate PL redox balance and ferroptosis are unknown. Lipoproteins, like high- and low-density lipoproteins (HDL and LDL), carry -toc in the circulation, which compelled our investigation of their role in -toc delivery and ferroptosis. Using cancer and neuronal cell models, here we show that lipoproteins, particularly HDL, deliver -toc by binding the cell membrane receptor scavenger receptor class B type 1 (SR-B1) to prevent ferroptosis. Additionally, we synthesized SR-B1 targeted HDL-like particles that contained -toc to validate data obtained with native lipoproteins. We reveal here a tunable cellular redox axis whereby native and synthetic HDLs containing -toc target SR-B1 to reduce PL-OOH and prevent ferroptosis.

cell biology↗

bioRxiv2023

Quantitative Geometric Modeling of Blood Cells from X-ray Histotomograms of Whole Zebrafish Larvae

Tissue phenotyping is foundational to understanding and assessing the cellular aspects of disease in organismal context and an important adjunct to molecular studies in the dissection of gene function, chemical effects, and disease. As a first step toward computational tissue phenotyping, we explore the potential of cellular phenotyping from 3-Dimensional (3D), 0.74 {micro}m isotropic voxel resolution, whole zebrafish larval images derived from X-ray histotomography, a form of micro-CT customized for histopathology. As proof of principle towards computational tissue phenotyping of cells, we created a semi-automated mechanism for the segmentation of blood cells in the vascular spaces of zebrafish larvae, followed by modeling and extraction of quantitative geometric parameters. Manually segmented cells were used to train a random forest classifier for blood cells, enabling the use of a generalized cellular segmentation algorithm for the accurate segmentation of blood cells. These models were used to create an automated data segmentation and analysis pipeline to guide the steps in a 3D workflow including blood cell region prediction, cell boundary extraction, and statistical characterization of 3D geometric and cytological features. We were able to distinguish blood cells at two stages in development (4- and 5-days-post-fertilization) and wild-type vs. polA2 huli hutu (hht) mutants. The application of geometric modeling across cell types to and across organisms and sample types may comprise a valuable foundation for computational phenotyping that is more open, informative, rapid, objective, and reproducible.

systems biology↗

bioRxiv2022

Web-based Histology Reference Atlas for the Freshwater Crustacean Daphnia magna

Daphnia are keystone species of freshwater habitats used as model organisms in ecology and evolutionary biology. Their small size, wide geographic distribution, and sensitivity to chemicals make them useful as environmental sentinels in regulatory toxicology and chemical risk assessment. Biomolecular (-omic) assessments of responses to chemical toxicity, which reveal detailed molecular signatures, become more powerful when correlated with other phenotypic outcomes (such as behavioral, physiological, or histopathological) for comparative validation and regulatory relevance. However, the lack of histopathology or tissue phenotype characterization of this species presently limits our ability to access cellular mechanisms of toxicity. Here, we address the central concept that interpreting aberrant tissue phenotypes requires a basic understanding of species normal microanatomy. We introduce the female and male Daphnia Histology Reference Atlas (DaHRA) for the baseline knowledge of Daphnia magna microanatomy. Additionally, we also included developmental stages of female Daphnia in this current atlas. This interactive web-based resource of adult Daphnia features overlaid vectorized demarcation of anatomical structures whose labels comply with an anatomical ontology created for this atlas. We demonstrate the potential utility of DaHRA for toxicological investigations by presenting aberrant phenotypes of acetaminophen-exposed D. magna. We envision DaHRA to facilitate the effort of integrating molecular and phenotypic data from the scientific community as we seek to understand how genes, chemicals, and environment interactions determine organismal phenotype.

zoology↗

bioRxiv2021

Whole-organism 3D Quantitative Characterization of Zebrafish Melanin by Silver Deposition Micro-CT

Melanin-rich zebrafish melanophores are used to study pigment development, human skin color, and as a large-scale screening phenotype. To facilitate more detailed whole-body, computational analyses of melanin content and morphology, we have combined X-ray microtomography (micro-CT), a non-destructive, full-volume imaging modality, with a novel application of ionic silver staining to characterize melanin distribution in whole zebrafish larvae. Normalized micro-CT reconstructions of silver-stained fish consistently reproduced pigment patterns seen by light microscopy, and allowed direct quantitative comparisons of melanin content across wild-type and mutant samples, for both dramatic and subtle phenotypes not previously described. Silver staining of melanin for micro-CT provides proof-of-principle for whole-body, three-dimensional computational phenomic analysis of a particular cell type at cellular resolution, with potential applications in other model organisms and human melanoma biopsies. Whole-organism, high-resolution phenotyping is a challenging ideal, but provides superior context for functional studies of mutations, diseases, and environmental influences.

pathology↗

bioRxiv2018

Three-Dimensional Histology of Whole Zebrafish by Sub-Micron Synchrotron X-ray Micro-Tomography

Histological studies providing cellular insights into tissue architecture have been central to biological discovery and remain clinically invaluable today. Extending histology to three dimensions would be transformational for research and diagnostics. However, three-dimensional histology is impractical using current techniques. We have customized sample preparation, synchrotron X-ray tomographic parameters, and three-dimensional image analysis to allow for complete histological phenotyping using whole larval and juvenile zebrafish. The resulting digital zebrafish can be virtually sectioned and visualized in any plane. Whole-animal reconstructions at subcellular resolution also enable computational characterization of the zebrafish nervous system by region-specific detection of cell nuclei and quantitative assessment of individual phenotypic variation. Three-dimensional histological phenotyping has potential use in genetic and chemical screens, and in clinical and toxicological tissue diagnostics.\n\nOne Sentence SummarySynchrotron X-ray micro-tomography can be used to rapidly create 3-dimensional images of fixed and stained specimens without sectioning, enabling computational histological phenotyping at cellular resolution.

pathology↗