HCV‐GLUE Web Resource

Overview

GLUE can be deployed within a standard web server, exposing its functionality via standard web service protocols for machine-to-machine interaction. By incorporating a web user interface (UI), GLUE projects can power dynamic web interfaces, where users can perform analyses, download data, and visualize results.

The HCV-GLUE project incorporates a web UI and can be deployed as a web application. A web instance of HCV-GLUE is hosted by the University of Glasgow, but is not being actively maintained.

Key Features of the Web Resource

1. Database of HCV Sequences and Metadata:

   • Comprehensive and Up-to-Date: HCV-GLUE maintains a daily updated database of HCV sequences and associated metadata sourced from NCBI, organized into clades by genotypes and subtypes. This data organization enables users to easily access and analyze the vast public sequence data.
   • Clade Assignments: The website provides an interface to HCV-GLUE's likelihood-based genotyping tools. Users can submit sequences and visualise genotyping results in phylogenetic context.

2. Pre-Built Multiple-Sequence Alignments:

   • Customizable Download Options: HCV-GLUE provides pre-built multiple-sequence alignments for all sequences stored in the database. Users can download alignments in sections defined by their specific research needs, making it easy to extract relevant data subsets for further analysis.
   • Alignment Tree Structure: The alignments are integrated into an alignment tree structure, which includes reference sequences for each constrained alignment node. This hierarchical organization supports complex comparative analyses across different HCV clades.

3. Drug Resistance Analysis:

   • Database of DAA-Resistant Polymorphisms: Developed in collaboration with the Virus Reference Department at Public Health England, HCV-GLUE includes a specialized database of polymorphisms associated with resistance to direct-acting antiviral drugs (DAAs). This database is crucial for studying and understanding resistance patterns in HCV.
   • Interactive Resistance Analysis Tool: The web interface offers an analysis tool that enables users to submit FASTA sequences for genotyping, drug resistance analysis, and visualization. The tool applies standardized numbering schemes to identify resistance-associated mutations, helping researchers and clinicians make informed decisions about treatment strategies.

4. Feature Definitions and Sequence Analysis:

   • Standardized Feature Definitions: In HCV-GLUE, the 5' and 3' untranslated regions (UTRs), the open reading frame (ORF) encoding the precursor polyprotein, and the ten mature viral proteins derived from it are defined as GLUE Features. These definitions align with the standardized numbering scheme proposed by Kuiken et al., allowing for precise and consistent analysis across studies.
   • Amino Acid Residue Analysis: HCV-GLUE provides commands for analyzing amino acid residues within sequences, enabling detailed studies of sequence variation and its implications for viral function, immune evasion, and drug resistance.

Advantages of GLUE as a Web Resource Back End

HCV-GLUE exemplifies how GLUE can serve as a robust back end for web applications focused on genomic data:

• Scalability and Flexibility: GLUE's data-centric architecture supports scalable integration of large genomic datasets and complex analyses. The web-based implementation of HCV-GLUE allows users to leverage these resources without needing to install or maintain local copies of the database.

• Daily Data Updates: The ability to integrate daily updates ensures that the HCV-GLUE resource remains current, providing the most up-to-date sequence information and analysis tools to users.

• Comprehensive Access: The entire HCV-GLUE dataset and its analysis functions are downloadable, enabling users to run private instances on local machines if desired. This flexibility supports diverse research needs, from web-based applications to private, offline analysis environments.

Summary

The web implementation of HCV-GLUE demonstrates the potential of GLUE-based resources in providing accessible, comprehensive, and flexible genomic analysis tools through a web interface. By integrating extensive data management capabilities with user-friendly online tools, HCV-GLUE empowers both researchers and clinicians to explore HCV sequence data and resistance patterns. Additionally, the ability to deploy GLUE within a standard web server and expose its functionality via web service protocols illustrates the versatility of GLUE resources for supporting both public-facing and internal computational infrastructure.