AUTHOR=Mai Hans-Jörg , Baby Dibin , Bauer Petra 

TITLE=Black sheep, dark horses, and colorful dogs: a review on the current state of the Gene Ontology with respect to iron homeostasis in Arabidopsis thaliana

JOURNAL=Frontiers in Plant Science

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/plant-science/articles/10.3389/fpls.2023.1204723

DOI=10.3389/fpls.2023.1204723

ISSN=1664-462X

ABSTRACT=Cellular homeostasis of the micronutrient iron is highly regulated in plants and responsive to nutri�on, stress and developmental signals. Genes for iron management encode metal and other transporters, enzymes synthesizing chelators and reducing substances, transcrip�on factors and several types of regulators. In transcriptome or proteome datasets, such iron homeostasis-related genes are frequently found to be differen�ally regulated. A common method to detect whether a specific cellular pathway is affected in the transcriptome data set is to perform Gene Ontology (GO) enrichment analysis. Hence, the GO database is a widely used resource for annota�ng genes and iden�fying enriched biological pathways in Arabidopsis thaliana. However, iron homeostasis-related GO terms do not consistently reflect gene associa�ons and levels of evidence in iron homeostasis. Some genes of the exis�ng iron homeostasis GO terms lack direct evidence of involvement in iron homeostasis. In other aspects, the exis�ng GO terms of iron homeostasis are incomplete and do not reflect the known biological func�ons associated with iron homeostasis. This can lead to poten�al errors in automa�c annota�on and interpreta�on of GO term enrichment analyses. We suggest that applicable evidence codes should be used to add missing genes and their respec�ve ortholog/paralog groups to make the iron homeostasisrelated GO terms more complete, and reliable. There is high likelihood of finding new iron homeostasisrelevant members in gene groups and families like the ZIP, ZIF, ZIFL, MTP, OPT, MATE, ABCG, PDR, HMA, and HMP. Hence, we compiled comprehensive lists of genes involved in iron homeostasis that can be used for custom enrichment analysis in transcriptomic or proteomic studies, including genes with direct experimental evidence, those regulated by central transcrip�on factors, and missing members of small gene families or ortholog/paralog groups. As we provide gene annota�on and literature alongside, the gene lists can serve in mul�ple computa�onal approaches. In summary, these gene lists provide a valuable resource for researchers studying iron homeostasis in A. thaliana, while they also emphasize the importance of improving the accuracy and comprehensiveness of the Gene Ontology.