Annotation data sets in FerrDb belong to three categories (Table 1). Genes were annotated as drivers, suppressors and markers. Small molecules were annotated as inducers and inhibitors. Drivers, suppressors, inducers and inhibitors are regulators of ferroptosis: drivers and inducers positively regulate ferroptosis, while suppressors and inhibitors negatively regulate ferroptosis. Markers do not regulate ferroptosis, but they indicate the occurrence of ferroptosis. Ferroptosis affects the development of disease in two ways. Ferroptosis was then annotated to either aggravate or alleviate an illness.
To be annotated as a ferroptosis regulator, genes and small molecules must possess explicit evidence to prove their regulatory role in ferroptosis. This kind of evidence is generally represented by an author statement of the role of the regulator in an original article. Genes that only undergo abundance, modification or stability change or are merely a component of a functional signaling axis or interaction network were annotated as markers. To annotate ferroptosis’ effect on diseases, evidence based on a growth test in cell lines or animal models was required.
In comparison with revealing a small molecule’s role, confirming a gene’s function is more challenging. We therefore dedicated more effort to gene annotation. A confidence level was assigned to each annotation to indicate its reliability (Table 2). Experimental reproducibility is correlated with results consistency, so the number of experiments was used as a score of the accuracy of the regulatory role of annotated genes. Critical cases (e.g. article retraction, conflicting results) that may affect the annotation reliability were highlighted by a caution statement. Other noteworthy information (e.g. inconsistent gene symbols) that seems less likely to impair annotation quality was denoted with a remark.
Free full text: Click here