Additional file 1 of Gene regulatory networks reveal sex difference in lung adenocarcinoma
Creators: name: Saha, Enakshi
name: Ben Guebila, Marouen
name: Fanfani, Viola
name: Fischer, Jonas
name: Shutta, Katherine H.
name: Mandros, Panagiotis
name: DeMeo, Dawn L.
name: Quackenbush, John
name: Lopes-Ramos, Camila M.
Publisher: name: figshare
Year: 2024
Subjects: subject: Genetics
subject: FOS: Biological sciences

description: Supplementary Material 1 A. Designing Sex-specific Transcription Factor-Gene Motif Prior. B. Designing Protein-protein Interaction Prior. C. Sex Difference in anti PD-1 and anti PDL-1 Inhibitors in Non-small Cell Lung Cancer. Figure D.6: Defining biological sex based on sex chromosome complement. Scatterplot of first two principal components of Y chromosome gene expression in GTEx (top left), TCGA (top right), LGRC (bottom left) and GSE68465 (bottom right). Figure D.1: Sex difference in LGRC control lung samples within nonsmokers and smokers. Normalized enrichment scores (NES) from GSEA using KEGG pathways are shown for all pathways that have significant (adjusted p-value &lt; 0.05) sex difference among either nonsmokers or smokers in LGRC. Pathways with higher targeting in male are marked blue and pathways with higher targeting in female are marked red. Green boxes highlight pathways associated with cell proliferation and brown boxes highlight pathways associated with environmental carcinogen metabolism. Figure D.2: Sex difference in tumor samples from the validation data GSE68465 within nonsmokers and smokers. Normalized enrichment scores (NES) from GSEA using KEGG pathways are shown for all pathways that have significant (adjusted p-value &lt; 0.05) sex difference among either nonsmokers or smokers (in TCGA). Pathways with higher targeting in male are marked blue and pathways with higher targeting in female are marked red. Green boxes highlight pathways associated with cell proliferation and purple boxes highlight pathways associated with immune response. Figure D.5: Sex difference in immune and stromal cell composition in GTEx samples: nonsmokers (left) and smokers (right). Cell compositions are computed using “xcell”, which derives cell composition proportion of 36 immune and stromal, along with three composite scores: immune score, stroma score and microenvironment score. The bubbleplot shows only those cells that are significantly (p-value &lt; 0.05) different in proportion in male and female samples. Figure D.7: Violinplot representing the distribution of XIST expression in samples from GTEx (left) and TCGA (right), split by smoking history. Figure D.3: Heatmap representing the t-statistics corresponding to the sex differences in the ribosomal pathway from the limma model for the samples from both GTEx and TCGA, split by their smoking history. From the heatmap we observed that the targeting patterns of the 85 ribosomal genes included in our analysis is distinct among GTEx nonsmokers, compared to the other three groups. A positive value of the t-statistics corresponds to higher targeting in females and a negative value corresponds to higher targeting in males. Genes with higher targeting in males are marked blue and genes with higher targeting in females are marked red. Figure D.4: Sex difference in tumor samples from the validation data GIS031 within nonsmokers and smokers. Normalized enrichment scores (NES) from GSEA using KEGG pathways are shown for all pathways that have significant (adjusted p-value &lt; 0.05) sex difference among either nonsmokers or smokers (in TCGA). A positive NES corresponds to higher targeting in females and a negative NES corresponds to higher targeting in males. Pathways with higher targeting in male are marked blue and pathways with higher targeting in female are marked red. Green boxes highlight pathways associated with cell proliferation and purple boxes highlight pathways associated with immune response. Table E.1: Distribution of Clinical Variables by Sex in GTEx. Table E.2: Distribution of Clinical Variables by Sex in TCGA. Table E.3: Distribution of Clinical Variables by Sex in LGRC. Table E.4: Distribution of Clinical Variables by Sex in GSE68465. Table E.5: Distribution of Clinical Variables among individuals who received chemotherapy versus those who did not, in TCGA dataset. F. Understanding Gene Regulatory Sex Differences in LUAD in East Asian Population.