scholarly journals Predicting tissue-specific gene expression from whole blood transcriptome

2021 ◽  
Vol 7 (14) ◽  
pp. eabd6991
Author(s):  
Mahashweta Basu ◽  
Kun Wang ◽  
Eytan Ruppin ◽  
Sridhar Hannenhalli
Keyword(s):  
Gene Expression ◽  
Whole Blood ◽  
Specific Gene ◽  
Specific Expression ◽  
Tissue Specific ◽  
Complex Disorders ◽  
Tissue Specific Gene ◽  
Tissue Specific Expression ◽  
Specific Gene Expression ◽  
Blood Transcriptome

Complex diseases are mediated via transcriptional dysregulation in multiple tissues. Thus, knowing an individual’s tissue-specific gene expression can provide critical information about her health. Unfortunately, for most tissues, the transcriptome cannot be obtained without invasive procedures. Could we, however, infer an individual’s tissue-specific expression from her whole blood transcriptome? Here, we rigorously address this question. We find that an individual’s whole blood transcriptome can significantly predict tissue-specific expression levels for ~60% of the genes on average across 32 tissues, with up to 81% of the genes in skeletal muscle. The tissue-specific expression inferred from the blood transcriptome is almost as good as the actual measured tissue expression in predicting disease state for six different complex disorders, including hypertension and type 2 diabetes, substantially surpassing the blood transcriptome. The code for tissue-specific gene expression prediction, TEEBoT, is provided, enabling others to study its potential translational value in other indications.

scholarly journals Predicting tissue-specific gene expression from whole blood transcriptome

2020 ◽  
Author(s):  
Mahashweta Basu ◽  
Kun Wang ◽  
Eytan Ruppin ◽  
Sridhar Hannenhalli
Keyword(s):  
Gene Expression ◽  
Whole Blood ◽  
Specific Gene ◽  
Specific Expression ◽  
Tissue Specific ◽  
Complex Disorders ◽  
Tissue Specific Gene ◽  
Tissue Specific Expression ◽  
Specific Gene Expression ◽  
Blood Transcriptome

AbstractComplex diseases are systemic, largely mediated via transcriptional dysregulation in multiple tissues. Thus, knowledge of tissue-specific transcriptome in an individual can provide important information about an individual’s health. Unfortunately, with a few exceptions such as blood, skin, and muscle, an individual’s tissue-specific transcriptome is not accessible through non-invasive means. However, due to shared genetics and regulatory programs between tissues, the transcriptome in blood may be predictive of those in other tissues, at least to some extent. Here, based on GTEx data, we address this question in a rigorous, systematic manner, for the first time. We find that an individual’s whole blood gene expression and splicing profile can predict tissue-specific expression levels in a significant manner (beyond demographic variables) for many genes. On average, across 32 tissues, the expression of about 60% of the genes is predictable from blood expression in a significant manner, with a maximum of 81% of the genes for the musculoskeletal tissue. Remarkably, the tissue-specific expression inferred from the blood transcriptome is almost as good as the actual measured tissue expression in predicting disease state for six different complex disorders, including Hypertension and Type 2 diabetes, substantially surpassing predictors built directly from the blood transcriptome. The code for our pipeline for tissue-specific gene expression prediction – TEEBoT, is provided, enabling others to study its potential translational value in other indications.

scholarly journals Methylation of the Cyclin A1 Promoter Correlates with Gene Silencing in Somatic Cell Lines, while Tissue-Specific Expression of Cyclin A1 Is Methylation Independent

2000 ◽  
Vol 20 (9) ◽  
pp. 3316-3329 ◽  
Author(s):  
Carsten Müller ◽  
Carol Readhead ◽  
Sven Diederichs ◽  
Gregory Idos ◽  
Rong Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Promoter Methylation ◽  
Cpg Island ◽  
Trichostatin A ◽  
Specific Gene ◽  
Cyclin A1 ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression

ABSTRACT Gene expression in mammalian organisms is regulated at multiple levels, including DNA accessibility for transcription factors and chromatin structure. Methylation of CpG dinucleotides is thought to be involved in imprinting and in the pathogenesis of cancer. However, the relevance of methylation for directing tissue-specific gene expression is highly controversial. The cyclin A1 gene is expressed in very few tissues, with high levels restricted to spermatogenesis and leukemic blasts. Here, we show that methylation of the CpG island of the human cyclin A1 promoter was correlated with nonexpression in cell lines, and the methyl-CpG binding protein MeCP2 suppressed transcription from the methylated cyclin A1 promoter. Repression could be relieved by trichostatin A. Silencing of a cyclin A1 promoter-enhanced green fluorescent protein (EGFP) transgene in stable transfected MG63 osteosarcoma cells was also closely associated with de novo promoter methylation. Cyclin A1 could be strongly induced in nonexpressing cell lines by trichostatin A but not by 5-aza-cytidine. The cyclin A1 promoter-EGFP construct directed tissue-specific expression in male germ cells of transgenic mice. Expression in the testes of these mice was independent of promoter methylation, and even strong promoter methylation did not suppress promoter activity. MeCP2 expression was notably absent in EGFP-expressing cells. Transcription from the transgenic cyclin A1 promoter was repressed in most organs outside the testis, even when the promoter was not methylated. These data show the association of methylation with silencing of the cyclin A1 gene in cancer cell lines. However, appropriate tissue-specific repression of the cyclin A1 promoter occurs independently of CpG methylation.

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

Food Shortage Causes Differential Effects on Body Composition and Tissue-Specific Gene Expression in Salmon Modified for Increased Growth Hormone Production

2015 ◽  
Vol 17 (6) ◽  
pp. 753-767 ◽  
Author(s):  
Jason Abernathy ◽  
Stéphane Panserat ◽  
Thomas Welker ◽  
Elisabeth Plagne-Juan ◽  
Dionne Sakhrani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Body Composition ◽  
Food Shortage ◽  
Specific Gene ◽  
Hormone Production ◽  
Tissue Specific ◽  
Differential Effects ◽  
Tissue Specific Gene ◽  
Specific Gene Expression

scholarly journals Blood—Brain Barrier Genomics

2001 ◽  
Vol 21 (1) ◽  
pp. 61-68 ◽  
Author(s):  
Jian Yi Li ◽  
Ruben J. Boado ◽  
William M. Pardridge
Keyword(s):  
Gene Expression ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Specific Gene ◽  
Microvascular Endothelium ◽  
Tissue Specific ◽  
Tissue Specific Gene ◽  
Specific Gene Expression ◽  
Blood Brain ◽  
Tester Cdna

The blood–brain barrier (BBB) is formed by the brain microvascular endothelium, and the unique transport properties of the BBB are derived from tissue-specific gene expression within this cell. The current studies developed a gene microarray approach specific for the BBB by purifying the initial mRNA from isolated rat brain capillaries to generate tester cDNA. A polymerase chain reaction–based subtraction cloning method, suppression subtractive hybridization (SSH), was used, and the BBB cDNA was subtracted with driver cDNA produced from mRNA isolated from rat liver and kidney. Screening 5% of the subtracted tester cDNA resulted in identification of 50 gene products and more than 80% of those were selectively expressed at the BBB; these included novel gene sequences not found in existing databases, ESTs, and known genes that were not known to be selectively expressed at the BBB. Genes in the latter category include tissue plasminogen activator, insulin-like growth factor-2, PC-3 gene product, myelin basic protein, regulator of G protein signaling 5, utrophin, IκB, connexin-45, the class I major histocompatibility complex, the rat homologue of the transcription factors hbrm or EZH1, and organic anion transporting polypeptide type 2. Knowledge of tissue-specific gene expression at the BBB could lead to new targets for brain drug delivery and could elucidate mechanisms of brain pathology at the microvascular level.

scholarly journals A new function for methyl CpG: Creating a C/EBPα binding site & mediating tissue‐specific gene expression

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Raghunath Chatterjee ◽  
Vikas Rishi ◽  
Julian Rozenberg ◽  
Paramita Bhattacharya ◽  
Kimberly Glass ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Site ◽  
Specific Gene ◽  
Tissue Specific ◽  
Tissue Specific Gene ◽  
Specific Gene Expression

scholarly journals Tissue-specific Gene Expression in Rat Hearts and Aortas in a Model of Vascular Nitrate Tolerance

2015 ◽  
Vol 65 (5) ◽  
pp. 485-493 ◽  
Author(s):  
Tamás Csont ◽  
Zsolt Murlasits ◽  
Dalma Ménesi ◽  
János Z. Kelemen ◽  
Péter Bencsik ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitrate Tolerance ◽  
Specific Gene ◽  
Tissue Specific ◽  
Tissue Specific Gene ◽  
Specific Gene Expression ◽  
Rat Hearts
Sign in / Sign up

Export Citation Format

Share Document