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Respiratory Virus Projects

Robert J. Gifford edited this page Nov 11, 2024 · 40 revisions

Overview

Respiratory viruses are a diverse group of pathogens that primarily infect the respiratory tract, leading to a range of diseases from mild upper respiratory infections to severe pneumonia. Key respiratory viruses include influenza viruses, respiratory syncytial virus (RSV), coronaviruses (such as SARS-CoV-2), rhinoviruses, and adenoviruses. These viruses are typically transmitted through respiratory droplets, aerosols, or direct contact with contaminated surfaces. The burden of respiratory viral infections is significant, particularly among vulnerable populations, including young children, the elderly, and individuals with underlying health conditions. Seasonal outbreaks and pandemics, such as the COVID-19 pandemic caused by SARS-CoV-2, highlight the potential for respiratory viruses to pose major public health challenges and strain healthcare systems globally.

Effective surveillance, prevention, and treatment strategies are essential for managing respiratory viral infections, while ongoing research is critical to enhance our understanding of respiratory viruses, including their transmission dynamics, pathogenic mechanisms, and the development of novel therapeutics and vaccines. Genomic data has an important role to play in addressing these issues, toward the goal of reducing the impact of respiratory viruses impact on global health.

GLUE projects have been developed for both influenza viruses and SARS-CoV-2, though each with distinct motivations. The SARS-CoV-2 resource was created in response to the urgent need for rapid deployment of tools during the COVID-19 pandemic. It provided researchers and public health agencies with critical genomic analysis capabilities to track the virus's spread and evolution in real time. In contrast, Flu-GLUE addresses a long-standing need in the influenza virus research community, where existing resources are built around a centralized "hub and spoke" model of data sharing. Flu-GLUE aims to shift toward a more decentralized approach, empowering researchers to share and analyze influenza genomic data more independently, fostering greater collaboration and accessibility across global research networks.



Contents

GLUE projects developed for respiratory viruses in the Gifford Lab:



Flu-GLUE

Background

Influenza viruses are known for causing seasonal epidemics of respiratory disease worldwide. Their ongoing evolution presents a significant public health challenge due to the emergence of new strains capable of causing seasonal outbreaks or even pandemics.

Scope & History

Flu-GLUE is an open resource supporting the comparative genomic analysis of influenza viruses. This resource facilitates the study of influenza A virus (IAV), influenza B virus (IBV), influenza C virus (ICV), and influenza D virus (IDV), emphasizing collaborative research through decentralized data sharing.

Flu-GLUE promotes a decentralized model where users can share data, tools, and insights directly with one another. This approach encourages a more dynamic exchange of knowledge, accelerating discoveries and improving responses to influenza outbreaks.

Through decentralized governance, Flu-GLUE facilitates direct interaction among researchers, allowing for shared tool development, data refinement, and the establishment of common standards and best practices. This ensures consistency and accuracy in genomic analysis across different projects. By enabling researchers to build on each other's work, Flu-GLUE strengthens collaboration, enhances reproducibility, and drives innovation in influenza research.

Features

  • Comprehensive Database: Flu-GLUE integrates influenza genome feature definitions, genome-length reference sequences, multiple sequence alignments, and standardized metadata for all major influenza lineages (IAV, IBV, ICV, IDV).

  • GLUE Framework Integration: Built on the GLUE software framework, Flu-GLUE offers an extensible platform for efficient, standardized, and reproducible genomic analysis of influenza viruses.

  • Phylogenetic Structure: Flu-GLUE organizes influenza virus sequence data in a phylogenetically structured manner, enabling easy exploration of evolutionary relationships among different virus strains.

  • Rich Annotations: Annotated reference sequences provide rigorous comparative genomic analysis capabilities related to conservation, viral adaptation, structural context, and genotype-to-phenotype associations.

  • Automated Genotyping: Flu-GLUE supports automated genotyping of influenza virus sequences (including subgenomic sequences) via GLUE's maximum likelihood clade assignment (MLCA) algorithm.

  • Collaborative and Decentralized: Flu-GLUE fosters direct collaboration between researchers, moving beyond the traditional hub-and-spoke model by promoting a decentralized system for data sharing and tool development.

  • GenBank Filtering Tools Integration: The inclusion of GenBank filtering tools enhances data quality and consistency, facilitating more accurate and reliable analyses.

  • Extensible Resource: The core Flu-GLUE project can be extended with additional layers, openly available via GitHub, enabling customized analyses and further project-specific developments.

Core Project Overview

Property Description
Scope Influenzaviruses (Genus Influenzavirus)
Development Period 2020-Present
Lead Developer Robert J. Gifford
Main Objectives Comparative Genomics, Epidemiological Monitoring, Variation Analysis
Data Sources NCBI
Associated Tools BLAST+, MAFFT, RAXML
Offline Project GitHub
Status Beta Version. Ongoing development 2024
User Guide GitHub Wiki

Extension Layers

  • Flu-GLUE-Reporter: Set-up for a IAV and IBV processing pipeine suitable for use for processing of clinical samples.
  • Flu-GLUE-Sentinel: An extension focused on sentinel surveillance.
  • Flu-GLUE-Architect: An extension focused on protein sequence and structure variants.


CoV-GLUE

Background

Scope & History

CoV-GLUE was developed and implemented quickly in response to the COVID-19 pandemic, going live on February 5, 2020. Hosted by the University of Glasgow Centre for Virus Research, it served as a key resource for analyzing SARS-CoV-2 genome sequences with a focus on tracking amino acid replacements and coding region indels. Users could submit their own sequences to receive interactive reports, which included visualizations of phylogenetic classification and highlighted potentially significant genomic variations, such as primer mismatches. CoV-GLUE also maintained a browsable database of observed amino acid variations across SARS-CoV-2 sequences from the pandemic.

Integrated with the COVID-19 Genomics UK (COG-UK) infrastructure, CoV-GLUE allowed broader access to GISAID and COG-UK datasets through a command-line interface on CLIMB, enabling scriptable analysis. In the earlier stages of the pandemic, CoV-GLUE was heavily utilized for tracking mutations and aiding molecular epidemiology efforts. However, as the pandemic progressed and millions of sequences became available, CoV-GLUE’s architecture could not scale to meet the growing demand.

The discontinuation of CoV-GLUE's development was closely tied to the departure of Josh Singer from the CVR, after which the project was no longer actively maintained. Despite its limitations in the later stages of the pandemic, CoV-GLUE played a critical role in early COVID-19 genomic research, especially for managing and analyzing SARS-CoV-2 sequences in the initial stages of the global response.

Key Features

  • Comprehensive database of amino acid replacements and coding region indels from SARS-CoV-2 sequences, continuously updated with data from GISAID and COG-UK.
  • Allows users to submit their own SARS-CoV-2 sequences for analysis, generating detailed, interactive reports with visualizations of phylogenetic classification, lineage assignment, and detection of significant genomic variations (e.g., primer mismatches, drug resistance mutations).
  • Tracks genetic variation across all viral proteins and regions, enabling real-time monitoring of mutations with potential implications for viral transmission, vaccine escape, and antiviral resistance.
  • Supports high-resolution queries, allowing users to filter sequence variations by protein, codon position, geographic region, collection date, or phylogenetic lineage.
  • Integrated with global data repositories (GISAID, COG-UK), enabling large-scale, comparative genomic analyses across a vast number of viral sequences.
  • Provides a robust command-line interface on CLIMB infrastructure for advanced, scriptable analysis of SARS-CoV-2 sequences, expanding its functionality beyond the web interface.
  • Facilitates molecular epidemiology studies by helping to identify emerging lineages, assess regional and temporal patterns in sequence variation, and track the global spread of mutations.

Core Project Overview

Property Description
Scope SARS coronavirus 2 (SARS-COV2)
Development Period 2019-2022
Lead Developer Josh Singer
Main Objectives Variation Analysis
Data Sources NCBI
Associated Tools BLAST+, MAFFT, RAXML
Offline Project GitHub Link
Online Access University of Glasgow CVR, (Discontinued)
Status Mature. Discontinued & not currently being developed
User Guide None available or planned


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