Empirical Gene Set Significance Test

To calculate the significance of differential expression of any given gene set M of size N, empirical distribution was determined. Specifically, differential expression of the set M was calculated as the average of the differential expression of genes of the set M, where the differential expression of each gene was quantified as: , which accounts for both fold change and P value of the differential expression. Then, a random gene set R of size N was sampled, and (i.e., average differential expression of genes in the set R) was calculated. Repeating this procedure 1E7 times, we constructed the empirical distribution of . P value of the significance of upregulation of M was calculated as , and significance of downregulation of M was calculated as
We compared cells of lymphoid lineage (i.e., CD4⁺ T, CD8⁺ T, B, and NK cells) between ESRRAi treatment and control (vehicle). The significance of the differential expression of a marker set is determined by the empirical distribution procedure described above.

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Sahu A., Wang X., Munson P., Klomp J.P., Wang X., Gu S.S., Han Y., Qian G., Nicol P., Zeng Z., Wang C., Tokheim C., Zhang W., Fu J., Wang J., Nair N.U., Rens J.A., Bourajjaj M., Jansen B., Leenders I., Lemmers J., Musters M., van Zanten S., van Zelst L., Worthington J., Liu J.S., Juric D., Meyer C.A., Oubrie A., Liu X.S., Fisher D.E, & Flaherty K.T. (2023). Discovery of Targets for Immune–Metabolic Antitumor Drugs Identifies Estrogen-Related Receptor Alpha. Cancer Discovery, 13(3), 672-701.

Publication 2023

Downregulation Expression genes Gene Lymphoid cells Nk cells Upregulation

Corresponding Organization : Massachusetts General Hospital

Other organizations : Chinese Academy of Medical Sciences & Peking Union Medical College, Shanghai Jiao Tong University, Shanghai Sixth People's Hospital, Tongji University, National Institutes of Health, National Cancer Institute

Top 5 similar protocols

Variable analysis

independent variables

ESRRAi treatment

dependent variables

Differential expression of genes in the set M
Empirical distribution of average differential expression of random gene set R

control variables

Vehicle (control)

controls

Vehicle (control)

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