Mitochondrial Genes and Annotations missing from EnrichGO

[Dragonmasterx87]

Hi Great tool thanks for maintaining it.

i have a question that relates to the lack of mitochondrial genome encoded genes and their corresponding ontologies.

In the following code:

hgnc <- c("MT-ATP6", "MT-ATP8", "MT-CO1", "MT-CO2", "MT-CO3", "MT-CYB", "MT-ND1", "MT-ND2", "MT-ND3", "MT-ND4", "MT-ND4L", "MT-ND5", "MT-ND6", "MT-RNR1", "MT-RNR2")
  
  # Run GO enrichment analysis genes up
  GO.up <- enrichGO(gene = hgnc , 
                    universe = all_genes, 
                    keyType = "SYMBOL", #keytypes(org.Hs.eg.db)
                    OrgDb = org.Hs.eg.db, 
                    ont = c("ALL"), 
                    pAdjustMethod = "BH", 
                    pvalueCutoff = 1, 
                    qvalueCutoff = 1, #if not set default is at 0.05
                    readable = TRUE)

I get a NULL, which is impossible because all these terms are part of multiple mitochondrial/ETC component annotations. I noticed that this could be a symbol issue, but upon using shorthand symbols (which is incorrect they should be HNGC) like ATP6, ATP8 etc, I found that the answer was still NULL.

However this could be a GO 2023 problem. If so, can one utilize older GO like from 2019 or 2018? If so how?

Thanks a lot.!

🐉

[guidohooiveld]

I believe the issue is that the hgnc symbols are not recognized c.q. compatible with the org.Hs.eg.db annotation, which is NCBI-based.

If the corresponding ENTREZID are used, GO terms are returned...

> library(org.Hs.eg.db)
> 
> hgnc <- c("MT-ATP6", "MT-ATP8", "MT-CO1", "MT-CO2", "MT-CO3", "MT-CYB", "MT-ND1", "MT-ND2",
+           "MT-ND3", "MT-ND4", "MT-ND4L", "MT-ND5", "MT-ND6", "MT-RNR1", "MT-RNR2")
> 
> ## nothing is found
> AnnotationDbi:::select(org.Hs.eg.db, keys = hgnc, keytype = "SYMBOL",
+                columns = c("ENTREZID", "SYMBOL", "GENENAME") )
Error in .testForValidKeys(x, keys, keytype, fks) : 
  None of the keys entered are valid keys for 'SYMBOL'. Please use the keys method to see a listing of valid arguments.
> 
> ## try ALIAS
> ## almost nothing is found
> AnnotationDbi:::select(org.Hs.eg.db, keys = hgnc, keytype = "ALIAS",
+                columns = c("ENTREZID", "SYMBOL", "GENENAME") )
'select()' returned 1:1 mapping between keys and columns
     ALIAS  ENTREZID   SYMBOL             GENENAME
1  MT-ATP6      <NA>     <NA>                 <NA>
2  MT-ATP8      <NA>     <NA>                 <NA>
3   MT-CO1      <NA>     <NA>                 <NA>
4   MT-CO2 107075310 MTCO2P12 MT-CO2 pseudogene 12
5   MT-CO3      <NA>     <NA>                 <NA>
6   MT-CYB      <NA>     <NA>                 <NA>
7   MT-ND1      <NA>     <NA>                 <NA>
8   MT-ND2      <NA>     <NA>                 <NA>
9   MT-ND3      <NA>     <NA>                 <NA>
10  MT-ND4      <NA>     <NA>                 <NA>
11 MT-ND4L      <NA>     <NA>                 <NA>
12  MT-ND5      <NA>     <NA>                 <NA>
13  MT-ND6      <NA>     <NA>                 <NA>
14 MT-RNR1      <NA>     <NA>                 <NA>
15 MT-RNR2      <NA>     <NA>                 <NA>
> 
> 
> ## manually look up your first 2 entries:
> ## MT-ATP6 has ENTREZID 4508 (https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7414)
> ## MT-ATP8 has ENTREZID 4509 (https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7415)
> 
> 
> AnnotationDbi:::select(org.Hs.eg.db, keys = c("4508","4509"), keytype = "ENTREZID",
+                columns = c("ENTREZID", "SYMBOL", "ALIAS", "GENENAME", "GOALL") ) [c(1:4, 1808:1812) ,]
'select()' returned 1:many mapping between keys and columns
     ENTREZID SYMBOL   ALIAS                  GENENAME      GOALL EVIDENCEALL
1        4508   ATP6 ATPase6 ATP synthase F0 subunit 6 GO:0003674         IBA
2        4508   ATP6 ATPase6 ATP synthase F0 subunit 6 GO:0003674         IDA
3        4508   ATP6 ATPase6 ATP synthase F0 subunit 6 GO:0003674         IPI
4        4508   ATP6 ATPase6 ATP synthase F0 subunit 6 GO:0003824         IBA
1808     4509   ATP8    ATP8 ATP synthase F0 subunit 8 GO:1902600         IEA
1809     4509   ATP8    ATP8 ATP synthase F0 subunit 8 GO:1904949         IBA
1810     4509   ATP8    ATP8 ATP synthase F0 subunit 8 GO:1904949         IDA
1811     4509   ATP8    ATP8 ATP synthase F0 subunit 8 GO:1904949         IEA
1812     4509   ATP8    ATP8 ATP synthase F0 subunit 8 GO:1904949         NAS
     ONTOLOGYALL
1             MF
2             MF
3             MF
4             MF
1808          BP
1809          CC
1810          CC
1811          CC
1812          CC
> 
> 
> packageVersion("org.Hs.eg.db")
[1] ‘3.19.1’
> 

LATER ADDED:
Yet, when you check the NCBI gene page for the first entry (4508) (here) the official symbol is MT-ATP6!

Mmm...?? Maybe something to report on the Bioconductor support forum?