Biology subjects

Davydov, A.

Publications and source records attributed to Davydov, A..

6 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

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↗

bioRxiv2023

Ultrasensitive allele inference from immune repertoire sequencing data with MiXCR

Allelic variability in the adaptive immune receptor loci, which harbor the gene segments that encode B cell and T cell receptors (BCR/TCR), has been shown to be of critical importance for immune responses to pathogens and vaccines. In recent years, B cell and T cell receptor repertoire sequencing (Rep-Seq) has become widespread in immunology research making it the most readily available source of information about allelic diversity in immunoglobulin (IG) and T cell receptor (TR) loci in different populations. Here we present a novel algorithm for extra-sensitive and specific variable (V) and joining (J) gene allele inference and genotyping allowing reconstruction of individual high-quality gene segment libraries. The approach can be applied for inferring allelic variants from peripheral blood lymphocyte BCR and TCR repertoire sequencing data, including hypermutated isotype-switched BCR sequences, thus allowing high-throughput genotyping and novel allele discovery from a wide variety of existing datasets. The developed algorithm is a part of the MiXCR software (https://mixcr.com) and can be incorporated into any pipeline utilizing upstream processing with MiXCR. We demonstrate the accuracy of this approach using Rep-Seq paired with long-read genomic sequencing data, comparing it to a widely used algorithm, TIgGER. We applied the algorithm to a large set of IG heavy chain (IGH) Rep-Seq data from 450 donors of ancestrally diverse population groups, and to the largest reported full-length TCR alpha and beta chain (TRA; TRB) Rep-Seq dataset, representing 134 individuals. This allowed us to assess the genetic diversity of genes within the IGH, TRA and TRB loci in different populations and demonstrate the connection between antibody repertoire gene usage and the number of allelic variants present in the population. Finally we established a database of allelic variants of V and J genes inferred from Rep-Seq data and their population frequencies with free public access at https://vdj.online.

immunology↗

bioRxiv2023

3D reconstructions of parasite development and the intracellular niche of the microsporidian pathogen E. intestinalis

Microsporidia are an early-diverging group of fungal pathogens that infect a wide range of hosts. Several microsporidian species infect humans, and infections can lead to fatal disease in immunocompromised individuals. As obligate intracellular parasites with highly reduced genomes, microsporidia are dependent on metabolites from their hosts for successful replication and development. Our knowledge of how microsporidian parasites develop inside the host remains rudimentary, and our understanding of the intracellular niche occupied by microsporidia has thus far relied largely on 2D TEM images and light microscopy. Here, we use serial block face scanning electron microscopy (SBF-SEM) to capture 3D snapshots of the human-infecting microsporidian, Encephalitozoon intestinalis, within host cells. We track the development of E. intestinalis through its life cycle, which allows us to propose a model for how its infection organelle, the polar tube, is assembled de novo in each developing spore. 3D reconstructions of parasite-infected cells provide insights into the physical interactions between host cell organelles and parasitophorous vacuoles, which contain the developing parasites. The host cell mitochondrial network is substantially remodeled during E. intestinalis infection, leading to mitochondrial fragmentation. SBF-SEM analysis shows changes in mitochondrial morphology in infected cells, and live-cell imaging provides insights into mitochondrial dynamics during infection. Together, our data provide insights into parasite development, polar tube assembly, and microsporidia-induced mitochondrial remodeling in the host cell.

microbiology↗

bioRxiv2023

Energetics of the Microsporidian Polar Tube Invasion Machinery

Microsporidia are eukaryotic, obligate intracellular parasites that infect a wide range of hosts, leading to health and economic burdens worldwide. Microsporidia use an unusual invasion organelle called the polar tube (PT), which is ejected from a dormant spore at ultra-fast speeds, to infect host cells. The mechanics of PT ejection are impressive. Anncaliia algerae microsporidia spores (3-4 {micro}m in size) shoot out a 100-nm-wide PT at a speed of 300 {micro}m/sec, creating a shear rate of 3000 sec-1. The infectious cargo, which contains two nuclei, is shot through this narrow tube for a distance of [~]60-140 {micro}m (Jaroenlak et al., 2020) and into the host cell. Considering the large hydraulic resistance in an extremely thin tube and the low-Reynolds-number nature of the process, it is not known how microsporidia can achieve this ultrafast event. In this study, we use Serial Block-Face Scanning Electron Microscopy to capture 3-dimensional snapshots of A. algerae spores in different states of the PT ejection process. Grounded in these data, we propose a theoretical framework starting with a systematic exploration of possible topological connectivity amongst organelles, and assess the energy requirements of the resulting models. We perform PT ring experiments in media of varying viscosity, and use the results to rank our proposed hypotheses based on their predicted energy requirement. We also present a possible mechanism for cargo translocation, and quantitatively compare our predictions to experimental observations. Our study provides a comprehensive biophysical analysis of the energy dissipation of microsporidian infection process and demonstrates the extreme limits of cellular hydraulics. Statement of SignicanceMicrosporidia are a group of spore-forming, intracellular parasites that infect a wide range of hosts (including humans). Once triggered, microsporidian spores (3-4 {micro}m in size) shoot out a specialized organelle called the polar tube (PT) (60-140 {micro}m long, 100 nm wide) at ultrafast speed (300 {micro}m/sec), penetrating host cells and acting as a conduit for the transport of infectious cargo. Although this process has fascinated biologists for a century, the biophysical mechanisms underlying PT extrusion are not understood. We thus take a data-driven approach to generate models for the physical basis of PT ring and cargo transport through the PT. Our approach here demonstrates the extreme limits of cellular hydraulics and the potential applications of biophysical approaches to other cellular architectures.

biophysics↗

bioRxiv2020

3-Dimensional Organization and Dynamics of the Microsporidian Polar Tube Invasion Machinery

Microsporidia, a divergent group of single-celled eukaryotic parasites, harness a specialized harpoon-like invasion apparatus called the polar tube (PT) to gain entry into host cells. The PT is tightly coiled within the transmissible extracellular spore, and is about 20 times the length of the spore. Once triggered, the PT is rapidly ejected and is thought to penetrate the host cell, acting as a conduit for the transfer of infectious cargo into the host. The organization of this specialized infection apparatus in the spore, how it is deployed, and how the nucleus and other large cargo are transported through the narrow PT are not well understood. Here we use serial block-face scanning electron microscopy to reveal the 3-dimensional architecture of the PT and its relative spatial orientation to other organelles within the spore. Using high-speed optical microscopy, we also capture and quantify the entire PT germination process in vitro. Our results show that the emerging PT experiences very high accelerating forces to reach velocities exceeding 300 m.s-1, and that firing kinetics differ markedly between species. Live-cell imaging reveals that the nucleus, which is approximately 7 times larger than the diameter of the PT, undergoes extreme deformation to fit through the narrow tube, and moves at speeds comparable to PT extension. Our study sheds new light on the 3-dimensional organization, dynamics, and mechanism of PT extrusion, and shows how infectious cargo moves through the tube to initiate infection.

microbiology↗