HIVed, a knowledgebase for differentially expressed human genes and proteins during HIV infection, replication and latency

Abstract

Measuring the altered gene expression level and identifying differentially expressed genes/proteins during HIV infection, replication and latency is fundamental for broadening our understanding of the mechanisms of HIV infection and T-cell dysfunction. Such studies are crucial for developing effective strategies for virus eradication from the body. Inspired by the availability and enrichment of gene expression data during HIV infection, replication and latency, in this study, we proposed a novel compendium termed HIVed (HIV expression database; http://hivlatency.erc.monash.edu/) that harbours comprehensive functional annotations of proteins, whose genes have been shown to be dysregulated during HIV infection, replication and latency using different experimental designs and measurements. We manually curated a variety of third-party databases for structural and functional annotations of the protein entries in HIVed. With the goal of benefiting HIV related research, we collected a number of biological annotations for all the entries in HIVed besides their expression profile, including basic protein information, Gene Ontology terms, secondary structure, HIV-1 interaction and pathway information. We hope this comprehensive protein-centric knowledgebase can bridge the gap between the understanding of differentially expressed genes and the functions of their protein products, facilitating the generation of novel hypotheses and treatment strategies to fight against the HIV pandemic.

Figure 1. The framework for constructing HIVed including curated gene expression and proteomics datasets, cross-referenced databases and technical support.

Figure 2. An overview of convenient functionalities provided by HIVed.

(a) Short paths provided on the home page. (b) A snapshot of the database statistics page. (c) Online documentation for database guidance. (d) User submission page.

Figure 3. Direct retrieval of database entries involved in the significantly enriched pathways using the pathway term ‘Epstein-Barr virus infection’ as an example.

Figure 4. Search functions provided in HIVed.

(a) Database ID search using UniProt ID. (b) Entry search using gene expression keywords.

Figure 5. A series of screenshots showing the detailed structural and functional annotations of a particular entry in the HIVed database.

(a) Overview of the webpage. (b) Protein basic information panel. (c) Gene expression panel. (d) Overview of protein functional site/domain using the Protein Feature View plug-in. (e) Drug-protein interaction panel. (f) Protein secondary structure panel with detailed portrait via the PV plug-in. (g) HIV-1 protein interaction panel. (h) Signalling/metabolic pathway panel.