I'm using the latest version of DAVID Knowledgebase (v2021q4, Available at david-d.ncifcrf.gov) for enrichment of a set of genes that I have. Using the Functional Annotation Table tool, I could download the annotations for the entire set of genes. However, the annotations obtained for few genes, particluarly from KEGG PATHWAY seem to be invalid. For instance, there is a gene in my dataset with Entrez Gene ID: 13389684. DAVID returned the following KEGG PATHWAY terms for this gene.
ldo04260:Cardiac muscle contraction,
ldo04932:Non-alcoholic fatty liver disease,
ldo05014:Amyotrophic lateral sclerosis,
ldo05022:Pathways of neurodegeneration - multiple diseases,
While cross-checking these pathways in KEGG, I found that all of these pathways (in fact a lot of pathways obtained for few other genes too!) are invalid. e.g this is what KEGG returns for ldo05208
According to the release notes, DAVID has integrated the October 1, 2021 release of KEGG database (Release 100.0) so technically it shouldn't return obsolete pathways. Is this an anomaly in DAVID or am I doing something wrong?
KEGG pathways in DAVID are mapped based on KEGG Orthologs. It seems that several genes for your species had orthologous genes in pathways that have not yet been annotated in KEGG for your species. KEGG pathways in the DAVID 2021 update have been updated to reflect these cases. Thank you again for bringing the situation to our attention.
Thank you for the clarification. But if a gene from my species has an orthologous gene in some pathway, the Ortholog Table for that pathway should display my species, right? But I can't find my species in that table. For instance, DAVID returned the pathway ldo05016:Huntington disease, for the gene 13389684. I looked at the Ortholog table for map05016 but my species seems to be missing. In fact there is no organism from the family which my gene belongs to. I'm curious to know how DAVID is assigning these pathways to my genes.
Entrez Gene Id 13389684 maps to Kegg Gene ldo:LDBPK_312650, specific for your organism. In that report, you will see that this KEGG Gene is associated with KEGG Ortholog K00416 which in turn is associated with map05016: Huntington Disease. However, there is no KEGG pathway specific to your species for Huntington Disease so thanks to your post, we have adjusted DAVID to not report pathways which fall into this situation.