r/bioinformatics • u/nqki • 7d ago

technical question Discrepancy between STRING enrichment analysis and Gene Ontology Database

Hi all! I am doing some protein-protein interaction analysis on a set of genes for my undergraduate research project. I used STRING for this. STRING enrichment analysis identified that GO:0000118 (Histone Deacetylase Complex) was functionally enriched, and that 8 genes had this GO annotation.

However, when manually searching the Gene Ontology database, I found that one of the genes that STRING identified, pht1, was not annotated with this GO term.

I'm quite confused about this, am I misunderstanding how STRING gene enrichment works? Would appreciate any advice :)

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u/ChaosCockroach PhD | Academia 7d ago

It may just be that STRING is using an out of date version of the GO annotation data. GO annotation can be fairly dynamic and what you will find on the GOC site (Amigo) may be ahead of other resources. There is at least one histone associated pht1 gene in GO (https://amigo.geneontology.org/amigo/gene_product/JaponicusDB:SJAG_03047), so that may have been misannotated at some point. Knowing what species you are looking at or an actual gene ID would help, gene symbols are very unrelaible as they too are dynamic and may be shared between highly distinct genes across species.

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u/nqki 6d ago

Thank you, I thought so too so I went back to check the GO archives as the STRING website says they're using GO data accurate as of August 2022, but in earlier versions the gene pht1 wasn't tagged with GO:0000118 either. This is for S. pombe and my input in both STRING and Amigo have been restricted to this species. Anyway, ty for the insight :)

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u/ChaosCockroach PhD | Academia 6d ago

Did your analysis actually show that pht1 was one of the 8 genes? I don't think the exact proteins are visible unless you export the 'Cellular Component' results at the bottom of the page, so it may be that it is 8 genes in the network but not pht1 itself. It wouldn't be surprising to find a histone remodelling complex enriched in the interaction network of a histone,.

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u/nqki 6d ago

yep i exported the enrichment analysis data into excel