Orthologous Clusters of Interferon-Stimulated Genes

One of the key innate immune mechanisms that antagonise virus infection in vertebrates is the interferon (IFN) system. Type I interferons (including IFN-β and IFN-α among others), type-II IFN (IFN-γ) and type III interferons (IFN-λ), are cytokines with immunomodulatory and proinflammatory properties. IFN signalling results in the upregulation of hundreds of interferon stimulated genes (ISGs), collectively referred to as the interferome, that initiate an antiviral state. This database catalogues the interferomes of ten different species, each derived from cells in an antiviral state following stimulation with type-I IFN. In this study an ISG is a gene upregulated with a false discovery rate (FDR) < 0.05, regardless of the extent to which it is upregulated. This can be adjusted in the user parameters.

Search clusters by gene symbol or ENSEMBL ID
* Search using an HGNC approved gene symbol.
Use the HGNC symbol checker to look up approved gene symbols.
Search clusters by presence / expression in specific species

Selected clusters must meet all of the following species criteria:

Ortholog:
Up-regulated gene:
Down-regulated gene:
{{species[speciesCriterion.species].displayName}} Ortholog:
Up-regulated gene:
Down-regulated gene:
Search clusters by presence / expression in a number of species

Selected clusters must meet all of the following criteria:

Orthologs must be present in at least species and at most species
Up-regulated genes must be present in at least species and at most species
Down-regulated genes must be present in at least species and at most species
Differential expression parameters How genes are classified as up-regulated or down-regulated:
Up-regulated genes: log2 FC > and FDR < {{geneRegulationParams.maxFDR}}
Down-regulated genes: log2 FC < and FDR < {{geneRegulationParams.maxFDR}}
False discovery rate: FDR <
User guide

Orthologous clusters

This database groups genes together in orthologous clusters, based on ENSEMBL annotations. Clusters may contain genes from different species i.e. orthologs. In some cases a gene has expanded within the species of a genome producing paralogs, so a cluster may also contain multiple genes from the same species.

For some clusters there was no ENSEMBL-annotated ortholog in the genome of a given species. Some of these absent orthologs have been resolved through a BLAST approach, and others via in silico 'baiting' for reads matching the ortholog of a closely related species. These genes are prefixed with 'CVR-defined gene'.

Within an orthologous cluster, the effect of interferon varies: some genes are up-regulated, others down-regulated, still others are not differentially expressed.

Searching

This web tool allows users to search for orthlogous clusters based on various kinds of search criteria.
Search clusters by gene symbol or ENSEMBL ID
Simply type in a gene symbol or ENSEMBL ID; the web tool will suggest matches from the database and return the cluster containing the specified gene. Approved gene symobls provided by the HUGO Gene Nomenclature Committee (HGNC) are accepted. For example, to search for RIG-I you will need to use DDX58. If you are unsure of the approved gene symbol, the HGNC symbol checker can be used to check.
Search clusters by presence / expression in specific species
Select clusters based on the presence and expression characteristics of genes in particular species. For example: "All clusters which contain orthologs in all the mammal species, including an up-regulated gene in humans and a down-regulated gene in cattle and sheep".
Search clusters by presence / expression in a number of species
Select clusters based on the presence and expression characteristics of genes in a certain number of species. For example: "All clusters which contain an ortholog in at least 5 species, including at least 3 species where there is an up-regulated gene".

Results

All clusters matching the criteria provided will be output. Clusters will specify all the genes within the cluster, grouped by species. Some species may not posess an ortholog within the cluster; these species will be absent.

If a gene's differential expression value is significant, it will have a red (significantly upregulated) or blue (significantly downregulated) arrow in the 'Expression' column, otherwise this column is blank.

Tables of search results can be downloaded in either tab-delimited or CSV format using the 'Download' button.

Differential expression parameters

This controls how genes are classified as up-regulated or down-regulated. Default values are set as any significant level of up-regulation (> 0) or down-regulation (< 0). The default value for significance is set at a false discovery rate (FDR) of 0.05. All these parameters may be edited; changing these values can affect which clusters are selected and how the 'Expression' result column is populated.

Results

No clusters found for this query

Clusters {{firstClusterIndex}} to {{lastClusterIndex}} of {{orthoClusters.length}}

Orthologous cluster ID Species ENSEMBL ID Gene Expression log2 Fold Change FDR
{{resultRow.orthoClusterId}} {{resultRow.species}} {{resultRow.ensemblId}} CVR-defined gene: {{resultRow.ensemblId}} {{resultRow.geneName}} {{resultRow.log2fc}} {{resultRow.fdr}}

Publication

PLOS Biology

Fundamental Properties of the Mammalian Innate Immune System Revealed by Multi-Species Comparison of Type I Interferon Responses

Andrew E. Shaw, Joseph Hughes, Quan Gu, Abdelkader Behdenna, Joshua B. Singer, Tristan Dennis, Richard J. Orton, Mariana Varela, Robert J. Gifford, Sam J. Wilson and Massimo Palmarini

Published December 18, 2017 : https://doi.org/10.1371/journal.pbio.2004086

Feedback

Contact Andrew Shaw with questions about the research or Josh Singer with any feedback on the web tool.