Dataset Information

Cross-tissue Analysis of Gene and Protein Expression in Normal and Cancer Tissues.

ABSTRACT: The central dogma of molecular biology describes the translation of genetic information from mRNA to protein, but does not specify the quantitation or timing of this process across the genome. We have analyzed protein and gene expression in a diverse set of human tissues. To study concordance and discordance of gene and protein expression, we integrated mass spectrometry data from the Human Proteome Map project and RNA-Seq measurements from the Genotype-Tissue Expression project. We analyzed 16,561 genes and the corresponding proteins in 14 tissue types across nearly 200 samples. A comprehensive tissue- and gene-specific analysis revealed that across the 14 tissues, correlation between mRNA and protein expression was positive and ranged from 0.36 to 0.5. We also identified 1,012 genes whose RNA and protein expression was correlated across all the tissues and examined genes and proteins that were concordantly and discordantly expressed for each tissue of interest. We extended our analysis to look for genes and proteins that were differentially correlated in cancer compared to normal tissues, showing higher levels of correlation in normal tissues. Finally, we explored the implications of these findings in the context of biomarker and drug target discovery.

SUBMITTER: Kosti I

PROVIDER: S-EPMC4855174 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Publications

Cross-tissue Analysis of Gene and Protein Expression in Normal and Cancer Tissues.

Kosti Idit I Jain Nishant N Aran Dvir D Butte Atul J AJ Sirota Marina M

Scientific reports 20160504

The central dogma of molecular biology describes the translation of genetic information from mRNA to protein, but does not specify the quantitation or timing of this process across the genome. We have analyzed protein and gene expression in a diverse set of human tissues. To study concordance and discordance of gene and protein expression, we integrated mass spectrometry data from the Human Proteome Map project and RNA-Seq measurements from the Genotype-Tissue Expression project. We analyzed 16, ...[more]

PMID: 27142790

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Project description:The genetic alterations that underlie cancer development are highly tissue-specific with the majority of driving alterations occurring in only a few cancer types and with alterations common to multiple cancer types often showing a tissue-specific functional impact. This tissue-specificity means that the biology of normal tissues carries important information regarding the pathophysiology of the associated cancers, information that can be leveraged to improve the power and accuracy of cancer genomic analyses. Research exploring the use of normal tissue data for the analysis of cancer genomics has primarily focused on the paired analysis of tumor and adjacent normal samples. Efforts to leverage the general characteristics of normal tissue for cancer analysis has received less attention with most investigations focusing on understanding the tissue-specific factors that lead to individual genomic alterations or dysregulated pathways within a single cancer type. To address this gap and support scenarios where adjacent normal tissue samples are not available, we explored the genome-wide association between the transcriptomes of 21 solid human cancers and their associated normal tissues as profiled in healthy individuals. While the average gene expression profiles of normal and cancerous tissue may appear distinct, with normal tissues more similar to other normal tissues than to the associated cancer types, when transformed into relative expression values, i.e., the ratio of expression in one tissue or cancer relative to the mean in other tissues or cancers, the close association between gene activity in normal tissues and related cancers is revealed. As we demonstrate through an analysis of tumor data from The Cancer Genome Atlas and normal tissue data from the Human Protein Atlas, this association between tissue-specific and cancer-specific expression values can be leveraged to improve the prognostic modeling of cancer, the comparative analysis of different cancer types, and the analysis of cancer and normal tissue pairs.

Dataset Information

Cross-tissue Analysis of Gene and Protein Expression in Normal and Cancer Tissues.

Publications

Cross-tissue Analysis of Gene and Protein Expression in Normal and Cancer Tissues.

Similar Datasets

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