Distribution of miRNA expression across human tissues

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Abstract

We present a human miRNA tissue atlas by determining the abundance of 1997 miRNAs in 61 tissue biopsies of different organs from two individuals collected post-mortem. One thousand three hundred sixty-four miRNAs were discovered in at least one tissue, 143 were present in each tissue. To define the distribution of miRNAs, we utilized a tissue specificity index (TSI). The majority of miRNAs (82.9%) fell in a middle TSI range i.e. were neither specific for single tissues (TSI > 0.85) nor housekeeping miRNAs (TSI < 0.5). Nonetheless, we observed many different miRNAs and miRNA families that were predominantly expressed in certain tissues. Clustering of miRNA abundances revealed that tissues like several areas of the brain clustered together. Considering -3p and -5p mature forms we observed miR-150 with different tissue specificity. Analysis of additional lung and prostate biopsies indicated that inter-organism variability was significantly lower than inter-organ variability. Tissue-specific differences between the miRNA patterns appeared not to be significantly altered by storage as shown for heart and lung tissue. MiRNAs TSI values of human tissues were significantly ( P = 10 ⁻⁸) correlated with those of rats; miRNAs that were highly abundant in certain human tissues were likewise abundant in according rat tissues. We implemented a web-based repository enabling scientists to access and browse the data ( https://ccb-web.cs.uni-saarland.de/tissueatlas).

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Variance stabilization applied to microarray data calibration and to the quantification of differential expression.

Wolfgang Huber, Anja von Heydebreck, Holger Sültmann … (2002)

We introduce a statistical model for microarray gene expression data that comprises data calibration, the quantification of differential expression, and the quantification of measurement error. In particular, we derive a transformation h for intensity measurements, and a difference statistic Deltah whose variance is approximately constant along the whole intensity range. This forms a basis for statistical inference from microarray data, and provides a rational data pre-processing strategy for multivariate analyses. For the transformation h, the parametric form h(x)=arsinh(a+bx) is derived from a model of the variance-versus-mean dependence for microarray intensity data, using the method of variance stabilizing transformations. For large intensities, h coincides with the logarithmic transformation, and Deltah with the log-ratio. The parameters of h together with those of the calibration between experiments are estimated with a robust variant of maximum-likelihood estimation. We demonstrate our approach on data sets from different experimental platforms, including two-colour cDNA arrays and a series of Affymetrix oligonucleotide arrays.

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Genome-wide midrange transcription profiles reveal expression level relationships in human tissue specification.

Itai Yanai, Hila Benjamin, Michael Shmoish … (2005)

Genes are often characterized dichotomously as either housekeeping or single-tissue specific. We conjectured that crucial functional information resides in genes with midrange profiles of expression. To obtain such novel information genome-wide, we have determined the mRNA expression levels for one of the largest hitherto analyzed set of 62 839 probesets in 12 representative normal human tissues. Indeed, when using a newly defined graded tissue specificity index tau, valued between 0 for housekeeping genes and 1 for tissue-specific genes, genes with midrange profiles having 0.15 50% of all expression patterns. We developed a binary classification, indicating for every gene the I(B) tissues in which it is overly expressed, and the 12-I(B) tissues in which it shows low expression. The 85 dominant midrange patterns with I(B)=2-11 were found to be bimodally distributed, and to contribute most significantly to the definition of tissue specification dendrograms. Our analyses provide a novel route to infer expression profiles for presumed ancestral nodes in the tissue dendrogram. Such definition has uncovered an unsuspected correlation, whereby de novo enhancement and diminution of gene expression go hand in hand. These findings highlight the importance of gene suppression events, with implications to the course of tissue specification in ontogeny and phylogeny. All data and analyses are publically available at the GeneNote website, http://genecards.weizmann.ac.il/genenote/ and, GEO accession GSE803. doron.lancet@weizmann.ac.il Four tables available at the above site.

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Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis.

Jian Xu, Chen Wu, Xu Che … (2011)

Numerous studies have shown that aberrant microRNA (miRNA) expression is associated with the development and progression of various types of human cancer and serum miRNAs are potential biomarkers. This study examined whether some commonly deregulated miRNAs in hepatocellular carcinoma (HCC) are presented in serum of patients with HCC and can serve as diagnostic markers. Serum miRNAs (miR-21, miR-122, and miR-223) were quantified by real-time quantitative RT-PCR in 101 patients with HCC and 89 healthy controls. In addition, 48 patients with chronic type B hepatitis were also analyzed for comparison. We found that the median levels of miR-21, miR-122, and miR-223 were significantly higher in patients with HCC than those in healthy controls (P = 7.48 x 10⁻¹³, P = 6.93 x 10⁻⁹, and P = 3.90 x 10⁻¹², respectively). However, these elevated serum miRNAs were also detected in patients with chronic hepatitis (P = 2.05 x 10⁻¹², P = 4.52 x 10⁻¹⁶, and P = 1.65 x 10⁻¹¹, respectively). Moreover, serum miR-21 and miR-122 in patients with chronic hepatitis were higher than in patients with HCC (P = 3.99 x 10⁻⁴ and P = 4.97 x 10⁻⁸), although no such significant difference was found for miR-223. Receiver-operator characteristic (ROC) curve analyses suggest that these serum miRNAs may be useful markers for discriminating patients with HCC or chronic hepatitis from healthy controls, but not patients with HCC from patients with chronic hepatitis. Our results indicate that serum miR-21, miR-122 and miR-223 are elevated in patients with HCC or chronic hepatitis and these miRNAs have strong potential to serve as novel biomarkers for liver injury but not specifically for HCC. Copyright © 2010 Wiley-Liss, Inc.

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Author and article information

Journal

Journal ID (nlm-ta): Nucleic Acids Res

Journal ID (iso-abbrev): Nucleic Acids Res

Journal ID (hwp): nar

Journal ID (publisher-id): nar

Title: Nucleic Acids Research

Publisher: Oxford University Press

ISSN (Print): 0305-1048

ISSN (Electronic): 1362-4962

Publication date (Print): 05 May 2016

Publication date (Electronic): 25 February 2016

Publication date PMC-release: 25 February 2016

Volume: 44

Issue: 8

Pages: 3865-3877

Affiliations

[1 ]Institute of Human Genetics, Saarland University, Medical School, Homburg, Germany

[2 ]Institute of Anatomy and Cell Biology, Saarland University, Medical School, Homburg, Germany

[3 ]Chair for Clinical Bioinformatics, Saarland University, Saarbruecken, Germany

[4 ]Department I of Internal Medicine and Center of Integrated Oncology, University Hospital of Cologne, Cologne, Germany

[5 ]Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany

[6 ]Department of Internal Medicine III, University Hospital Heidelberg, 69120 Heidelberg, Germany

[7 ]German Center for Cardiovascular Research (DZHK), 69120 Heidelberg, Germany

[8 ]Klaus Tschira Institute for Integrative Computational Cardiology, D-69118 Heidelberg, Germany

[9 ]Siemens Healthcare, Hartmannstrasse 16, 91052 Erlangen, Germany

Author notes

[* ]To whom correspondence should be addressed. Tel: +49 681 302 68611; Fax: +49 681 302 58094; Email: andreas.keller@ 123456ccb.uni-saarland.de

Article

DOI: 10.1093/nar/gkw116

PMC ID: 4856985

PubMed ID: 26921406

SO-VID: 63c733ef-e4f0-4eec-b1f3-e25b9d006ac7

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

History

Date accepted : 17 February 2016

Date revision received : 17 February 2016

Date received : 06 May 2015

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Pages: 13

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cover-date 05 May 2016

ScienceOpen disciplines: Genetics

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ScienceOpen disciplines: Genetics

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Distribution of miRNA expression across human tissues

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RNA drug delivery

Most cited references 19

Variance stabilization applied to microarray data calibration and to the quantification of differential expression.

Genome-wide midrange transcription profiles reveal expression level relationships in human tissue specification.

Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis.

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Cited by 429

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