Error Report: Incorrect Annotation of Gene Sets FOSTER_TOLERANT_MACROPHAGE_DN and FOSTER_TOLERANT_MACROPHAGE_UP in GSEA

[钟恺]

Dear GSEA Administrator,I am writing to report an annotation error in the GSEA/MSigDB database for the human gene sets "FOSTER_TOLERANT_MACROPHAGE_DN" and "FOSTER_TOLERANT_MACROPHAGE_UP". These gene sets are derived from the literature: Foster et al., 2007, "Gene-specific control of inflammation by TLR-induced chromatin modifications" (Nature, DOI: 10.1038/nature05836).Issue Description:​The current "Brief description" for these gene sets in GSEA is inconsistent with the original article. Specifically:

• The gene set "FOSTER_TOLERANT_MACROPHAGE_DN"​ is incorrectly described as corresponding to Class NT (non-tolerizable) genes.
• According to the article, Class NT genes are defined as genes induced during the first LPS stimulation and expressed at equal or higher levels in tolerant macrophages (i.e., (N+L)/(T+L) ≤ 1). These genes should be associated with an "UP" suffix, indicating up-regulation.
• However, the gene set "FOSTER_TOLERANT_MACROPHAGE_DN"​ (with "DN" suffix) should correctly correspond to Class T (tolerizable) genes, which are defined as genes induced during the first LPS stimulation and downregulated more than 3-fold in tolerant macrophages (i.e., (N+L)/(T+L) > 3). This is explicitly stated in the article's Methods section.

Evidence from Literature:​The article defines:

• Class T genes: "genes induced in naive macrophages stimulated with LPS and downregulated more than 3-fold in tolerant macrophages stimulated with LPS (that is, (N+L)/(T+L) > 3)."
• Class NT genes: "genes induced in naive macrophages stimulated with LPS and expressed at equal or higher levels in tolerant macrophages stimulated with LPS (that is, (N+L)/(T+L) ≤ 1)."This is supported by experimental results in Fig. 1e of the article, which shows qPCR validation of gene expression differences.

Suggested Corrections:​To align with the original literature, I recommend updating the "Brief description" in GSEA as follows:

• For "FOSTER_TOLERANT_MACROPHAGE_DN":Correct the description to: "Class T (tolerizable) genes: induced during the first LPS stimulation and not re-induced or induced to a much lesser degree in tolerant macrophages (as defined by (N+L)/(T+L) > 3)."
• For "FOSTER_TOLERANT_MACROPHAGE_UP":Correct the description to: "Class NT (non-tolerizable) genes: induced during the first LPS stimulation and induced at equal or greater degree in tolerant macrophages (as defined by (N+L)/(T+L) ≤ 1)."

This correction will ensure the database accurately reflects the scientific findings and improves reliability for users. I have attached relevant screenshots from the article and GSEA for your reference.Thank you for your attention to this matter. I am available to provide additional details if needed.
Best regards,​Kai Zhong