scholarly journals De novo discovery of a tissue-specific gene regulatory module in a chordate

2005 ◽  
Vol 15 (10) ◽  
pp. 1315-1324 ◽  
Author(s):  
D. S. Johnson
Keyword(s):  
De Novo ◽  
Specific Gene ◽  
Tissue Specific ◽  
Tissue Specific Gene ◽  
Regulatory Module ◽  
Gene Regulatory

scholarly journals Gene Networks and Pathways for Plasma Lipid Traits via Multi-tissue Multi-omics Systems Analysis

2020 ◽  
pp. jlr.RA120000713
Author(s):  
Montgomery Blencowe ◽  
In Sook Ahn ◽  
Zara Saleem ◽  
Helen Luk ◽  
Ingrid Cely ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Gene Regulatory Networks ◽  
Lipid Content ◽  
Regulatory Networks ◽  
Plasma Lipid ◽  
Specific Gene ◽  
Tissue Specific ◽  
Tissue Specific Gene ◽  
Gene Regulatory ◽  
Lipid Regulation

Genome-wide association studies (GWAS) have implicated ~380 genetic loci for plasma lipid regulation. However, these loci only explain 17-27% of the trait variance and a comprehensive understanding of the molecular mechanisms has not been achieved. In this study, we utilized an integrative genomics approach leveraging diverse genomic data from human populations to investigate whether genetic variants associated with various plasma lipid traits, namely total cholesterol (TC), high and low density lipoprotein cholesterol (HDL and LDL), and triglycerides (TG), from GWAS were concentrated on specific parts of tissue-specific gene regulatory networks. In addition to the expected lipid metabolism pathways, gene subnetworks involved in ‘interferon signaling’, ‘autoimmune/immune activation’, ‘visual transduction’, and ‘protein catabolism’ were significantly associated with all lipid traits. Additionally, we detected trait-specific subnetworks, including cadherin-associated subnetworks for LDL, glutathione metabolism for HDL, valine, leucine and isoleucine biosynthesis for TC, and insulin signaling and complement pathways for TG. Finally, utilizing gene-gene relations revealed by tissue-specific gene regulatory networks, we detected both known (e.g. APOH, APOA4, and ABCA1) and novel (e.g. F2 in adipose tissue) key regulator genes in these lipid-associated subnetworks. Knockdown of the F2 gene (Coagulation Factor II, Thrombin) in 3T3-L1 and C3H10T1/2 adipocytes reduced gene expression of Abcb11, Apoa5, Apof, Fabp1, Lipc, and Cd36, reduced intracellular adipocyte lipid content, and increased extracellular lipid content, supporting a link between adipose thrombin and lipid regulation. Our results shed light on the complex mechanisms underlying lipid metabolism and highlight potential novel targets for lipid regulation and lipid-associated diseases.

scholarly journals Sharing and specificity of co-expression networks across 35 human tissues

2014 ◽  
Author(s):  
Emma Pierson ◽  
GTEx Consortium ◽  
Daphne Koller ◽  
Alexis Battle ◽  
Sara Mostafavi
Keyword(s):  
Regulatory Networks ◽  
Specific Gene ◽  
Human Tissues ◽  
Expression Data ◽  
Rna Seq ◽  
Web Tool ◽  
Tissue Specific ◽  
Tissue Specific Gene ◽  
Share Data ◽  
Gene Regulatory

To understand the regulation of tissue-specific gene expression, the GTEx Consortium generated RNA-seq expression data for more than thirty distinct human tissues. This data provides an opportunity for deriving shared and tissue-specific gene regulatory networks on the basis of co-expression between genes. However, a small number of samples are available for a majority of the tissues, and therefore statistical inference of networks in this setting is highly underpowered. To address this problem, we infer tissue-specific gene co-expression networks for 35 tissues in the GTEx dataset using a novel algorithm, GNAT, that uses a hierarchy of tissues to share data between related tissues. We show that this transfer learning approach increases the accuracy with which networks are learned. Analysis of these networks reveals that tissue-specific transcription factors are hubs that preferentially connect to genes with tissue-specific functions. Additionally, we observe that genes with tissue-specific functions lie at the peripheries of our networks. We identify numerous modules enriched for Gene Ontology functions, and show that modules conserved across tissues are especially likely to have functions common to all tissues, while modules that are upregulated in a particular tissue are often instrumental to tissue-specific function. Finally, we provide a web tool, available at mostafavilab.stat.ubc.ca/GNAT, which allows exploration of gene function and regulation in a tissue-specific manner.

scholarly journals Gene Networks and Pathways for Plasma Lipid Traits via Multi-tissue Multi-omics Systems Analysis

2020 ◽  
Author(s):  
Montgomery Blencowe ◽  
In Sook Ahn ◽  
Zara Saleem ◽  
Helen Luk ◽  
Ingrid Cely ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Gene Regulatory Networks ◽  
Lipid Content ◽  
Regulatory Networks ◽  
Plasma Lipid ◽  
Specific Gene ◽  
Tissue Specific ◽  
Tissue Specific Gene ◽  
Gene Regulatory ◽  
Lipid Regulation

AbstractGenome-wide association studies (GWAS) have implicated ∼380 genetic loci for plasma lipid regulation. However, these loci only explain 17-27% of the trait variance and a comprehensive understanding of the molecular mechanisms has not been achieved. In this study, we utilized an integrative genomics approach leveraging diverse genomic data from human populations to investigate whether genetic variants associated with various plasma lipid traits, namely total cholesterol (TC), high and low density lipoprotein cholesterol (HDL and LDL), and triglycerides (TG), from GWAS were concentrated on specific parts of tissue-specific gene regulatory networks. In addition to the expected lipid metabolism pathways, gene subnetworks involved in ‘interferon signaling’, ‘autoimmune/immune activation’, ‘visual transduction’, and ‘protein catabolism’ were significantly associated with all lipid traits. Additionally, we detected trait-specific subnetworks, including cadherin-associated subnetworks for LDL, glutathione metabolism for HDL, valine, leucine and isoleucine biosynthesis for TC, and insulin signaling and complement pathways for TG. Finally, utilizing gene-gene relations revealed by tissue-specific gene regulatory networks, we detected both known (e.g. APOH, APOA4, and ABCA1) and novel (e.g. F2 in adipose tissue) key regulator genes in these lipid-associated subnetworks. Knockdown of the F2 gene (Coagulation Factor II, Thrombin) in 3T3-L1 and C3H10T1/2 adipocytes reduced gene expression of Abcb11, Apoa5, Apof, Fabp1, Lipc, and Cd36, reduced intracellular adipocyte lipid content, and increased extracellular lipid content, supporting a link between adipose thrombin and lipid regulation. Our results shed light on the complex mechanisms underlying lipid metabolism and highlight potential novel targets for lipid regulation and lipid-associated diseases.

scholarly journals A unique histone 3 lysine 14 chromatin signature underlies tissue-specific gene regulation

2021 ◽  
Author(s):  
Isabel Regadas ◽  
Olle Dahlberg ◽  
Roshan Vaid ◽  
Oanh Ho ◽  
Sergey Belikov ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Specific Gene ◽  
Chromatin Signature ◽  
Tissue Specific ◽  
Tissue Specific Gene ◽  
Histone 3

Histones: genetic diversity and tissue-specific gene expression

1997 ◽  
Vol 107 (1) ◽  
pp. 1-10 ◽  
Author(s):  
D. Doenecke ◽  
W. Albig ◽  
C. Bode ◽  
B. Drabent ◽  
K. Franke ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genetic Diversity ◽  
Specific Gene ◽  
Tissue Specific ◽  
Tissue Specific Gene ◽  
Specific Gene Expression
Sign in / Sign up

Export Citation Format

Share Document