Shared and distinct pathways and networks genetically linked to coronary artery disease between human and mouse
- Department of Integrative Biology and Physiology, University of California, Los Angeles, United States
- The Information School at the University of Sheffield, United Kingdom
- Interdepartmental Program of Molecular, Cellular and Integrative Physiology, University of California, Los Angeles, United States
- Department of Medicine, Division of Cardiology, University of California, Los Angeles, United States
- Department of Genetics & Genomic Sciences, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, United States
- Department of Medicine, (Huddinge), Karolinska Institutet, Sweden
- Departments of Human Genetics & Microbiology, Immunology, and Molecular Genetics, UCLA, United States
- Cardiovascular Research Laboratory, David Geffen School of Medicine, UCLA, United States
- Interdepartmental Program of Bioinformatics, University of California, Los Angeles, United States
- Department of Molecular and Medical Pharmacology, University of California, Los Angeles, United States
Figures
Figure 1
Overview of Study.
Figure 2
Shared and species-specific biological pathways.
(A) Bar plot highlighting the number of significant pathways shared and unique between mouse and human in vascular tissue (FDR<0.05). (B) Venn diagram highlighting the top shared and unique significant pathways between mouse and human in vascular tissue. (C) Bar plot highlighting the number of significant pathways shared and unique between mouse and human in non-vascular tissue (liver) (FDR<0.05). (D) Venn diagram highlighting the top shared and unique significant pathways between mouse and human in non-vascular tissue (liver).
Figure 3
Shared networks between mice and humans.
(A) Vascular tissue gene regulatory network shared between mice and humans (B) Non-vascular gene regulatory network shared between mice and humans. Each node is color coded based on the pathway/module that the genes are derived from with larger nodes signifying key driver genes. Red border diamonds represent CAD GWAS hits uncovered after the CARDIOGRAM+C4D GWAS (2016 onwards) and pink border diamonds represent CAD GWAS hits prior to the CARDIOGRAM+C4D GWAS.
Figure 4
Species-specific networks.
(A) Human vascular gene regulatory network, (B) Human non-vascular gene regulatory network, (C) Mouse vascular gene regulatory network, (D) Mouse non-vascular gene regulatory network. Each node is color coded based on the pathway/module that the genes are derived from with larger nodes signifying key driver genes. Red border diamonds represent CAD GWAS hits uncovered after the CARDIOGRAM+C4D GWAS (2016 onwards) and pink border diamonds represent CAD GWAS hits prior to the CARDIOGRAM+C4D GWAS.
Figure 5
In silico validation of select KDs using single cell RNA-sequencing data.
(A-D) Aorta KDs and subnetwork genes, where AvgLog2(FC) is representing gene expression change between atherogenic diet and chow diet groups. (E-H) Liver OIT3 KD and subnetwork genes, where AvgLog2(FC) is representing gene expression changes between NASH and control. The last 5 genes in each plot are randomly selected negative control genes. We utilized a Wilcoxon rank sum test with bonferroni correction to derive significance for each gene. * represents a p<0.05.
Additional files
-
Supplementary file 1
Co-expression module numbers, MSEA pathway results and KD correlations with CAD clinical traits.
(A) The number of modules derived from WGCNA and MEGENA from vascular and non-vascular tissues. (B) Marker Set Enrichment Analysis (MSEA) results with an FDR <5% for Human CAD GWAS and Mouse atherosclerosis GWAS in vascular and non-vascular tissue. (C) Second round of MSEA results for the independent supersets with an FDR <5% and cross-species comparison. (D) Key driver correlations in vascular tissue with clinical traits relevant to CAD. (E) Key driver correlations in non-vascular tissue with clinical traits relevant to CAD.
- https://cdn.elifesciences.org/articles/88266/elife-88266-supp1-v1.xlsx
-
MDAR checklist
- https://cdn.elifesciences.org/articles/88266/elife-88266-mdarchecklist1-v1.docx
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Shared and distinct pathways and networks genetically linked to coronary artery disease between human and mouse
eLife 12:RP88266.
https://doi.org/10.7554/eLife.88266.3
