Li et al., 2019 ). The numbers of genes that fulfill each or several of these criteria are listed in the Venn diagram. (D) Heatmap listing the genes under the plasma TUDCA QTL at T30 on chromosome 8 reveals the potential modulators of TUDCA. Only genes fulfilling at least 2 criteria were included in the heatmap. The first block of the heatmap represents whether the genes have high-impact variants or cis -eQTLs in liver transcriptome datasets of the BXDs. The second block (Corr) indicates the correlations between the liver expression of these genes and plasma TUDCA levels at T30 in CD or HFD. The third block shows the association between these genes and the primary BA biosynthesis pathway predicted by GMAD (
Li et al., 2019 ) in human, mouse, and rat. The last block shows the enrichment of the expression of these genes in the liver, retrieved from the Human Protein Atlas ( https://www.proteinatlas.org/ ) (
Uhlén et al., 2015 ). r , Pearson correlation coefficient. GMAS, gene-module association score. Asterisk ( ∗ p < 0.05) and hash (#) indicate statistical significance in correlation and GMAD, respectively. The 3 selected candidates are in bold and underlined. Full list of the 191 genes under the TUDCA QTL on chromosome 8 is in
Table S7 . (E) Zonation protein (left) or mRNA (right) profiles of key BA synthesis and transport genes, as well as candidate TUDCA modulators in the mouse liver. Protein or mRNA expression of each gene was scaled to 0–1. See also
Figure S6 and
Tables S1 , , and . " width="100%" height="100%">
Journal: Cell Metabolism
Article Title: Integrative systems analysis identifies genetic and dietary modulators of bile acid homeostasis
doi: 10.1016/j.cmet.2022.08.015
Figure Lengend Snippet: Genetic mapping of BA modulators and the identification of Ces1c as a potential regulator of plasma TUDCA levels (A) The genetic effects of the TUDCA QTL on chromosome 8 on plasma TUDCA levels of the BXD animals at 30 min after a test meal. Plasma TUDCA concentrations (log 2 transformed data) were compared between strains inheriting the genetic allele from the reference C57BL/6J strain at the QTL (indicated as B/B) and those inheriting from the DBA/2J strain (indicated as D/D). ∗∗∗ p < 0.001 by two-tailed Student’s t test. (B) Heatmap presenting the correlations between the TUDCA levels across different biological compartments and phenotypic traits. ∗ p < 0.05, ∗∗ p < 0.01, and ∗∗∗ p < 0.001, for Pearson correlation coefficient. (C) Systems genetics pipeline applied to filter for genes responsible for the plasma TUDCA QTL at T30 by integrating 3 major criteria, that is, (1) whether genes have high-impact genetic variants or cis -eQTLs in the liver, (2) whether their liver expression level correlates with plasma TUDCA levels at T30, and (3) whether they associate with the primary BA biosynthesis (KEGG 0120) pathway in GMAD ( Li et al., 2019 ). The numbers of genes that fulfill each or several of these criteria are listed in the Venn diagram. (D) Heatmap listing the genes under the plasma TUDCA QTL at T30 on chromosome 8 reveals the potential modulators of TUDCA. Only genes fulfilling at least 2 criteria were included in the heatmap. The first block of the heatmap represents whether the genes have high-impact variants or cis -eQTLs in liver transcriptome datasets of the BXDs. The second block (Corr) indicates the correlations between the liver expression of these genes and plasma TUDCA levels at T30 in CD or HFD. The third block shows the association between these genes and the primary BA biosynthesis pathway predicted by GMAD ( Li et al., 2019 ) in human, mouse, and rat. The last block shows the enrichment of the expression of these genes in the liver, retrieved from the Human Protein Atlas ( https://www.proteinatlas.org/ ) ( Uhlén et al., 2015 ). r , Pearson correlation coefficient. GMAS, gene-module association score. Asterisk ( ∗ p < 0.05) and hash (#) indicate statistical significance in correlation and GMAD, respectively. The 3 selected candidates are in bold and underlined. Full list of the 191 genes under the TUDCA QTL on chromosome 8 is in Table S7 . (E) Zonation protein (left) or mRNA (right) profiles of key BA synthesis and transport genes, as well as candidate TUDCA modulators in the mouse liver. Protein or mRNA expression of each gene was scaled to 0–1. See also Figure S6 and Tables S1 , , and .
Article Snippet: The tissue specificity gene expression data was downloaded from the Human Protein Atlas ( https://proteinatlas.org/humanproteome/tissue/liver ) ( ) on 2019.12.18.
Techniques: Clinical Proteomics, Transformation Assay, Two Tailed Test, Expressing, Blocking Assay
