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Preservation of ranking order in the expression of human Housekeeping genes.

ABSTRACT: Housekeeping (HK) genes fulfill the basic needs for a cell to survive and function properly. Their ubiquitous expression, originally thought to be constant, can vary from tissue to tissue, but this variation remains largely uncharacterized and it could not be explained by previously identified properties of HK genes such as short gene length and high GC content. By analyzing microarray expression data for human genes, we uncovered a previously unnoted characteristic of HK gene expression, namely that the ranking order of their expression levels tends to be preserved from one tissue to another. Further analysis by tensor product decomposition and pathway stratification identified three main factors of the observed ranking preservation, namely that, compared to those of non-HK (NHK) genes, the expression levels of HK genes show a greater degree of dispersion (less overlap), stableness (a smaller variation in expression between tissues), and correlation of expression. Our results shed light on regulatory mechanisms of HK gene expression that are probably different for different HK genes or pathways, but are consistent and coordinated in different tissues.

SUBMITTER: Shaw GT

PROVIDER: S-EPMC3245260 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Preservation of ranking order in the expression of human Housekeeping genes.

Shaw Grace T W GT Shih Edward S C ES Chen Chun-Houh CH Hwang Ming-Jing MJ

PloS one 20111222 12

Housekeeping (HK) genes fulfill the basic needs for a cell to survive and function properly. Their ubiquitous expression, originally thought to be constant, can vary from tissue to tissue, but this variation remains largely uncharacterized and it could not be explained by previously identified properties of HK genes such as short gene length and high GC content. By analyzing microarray expression data for human genes, we uncovered a previously unnoted characteristic of HK gene expression, namely ...[more]

PMID: 22216246

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Project description:The ideal reference, or control, gene for the study of gene expression in a given organism should be expressed at a medium‑high level for easy detection, should be expressed at a constant/stable level throughout different cell types and within the same cell type undergoing different treatments, and should maintain these features through as many different tissues of the organism. From a biological point of view, these theoretical requirements of an ideal reference gene appear to be best suited to housekeeping (HK) genes. Recent advancements in the quality and completeness of human expression microarray data and in their statistical analysis may provide new clues toward the quantitative standardization of human gene expression studies in biology and medicine, both cross‑ and within‑tissue. The systematic approach used by the present study is based on the Transcriptome Mapper tool and exploits the automated reassignment of probes to corresponding genes, intra‑ and inter‑sample normalization, elaboration and representation of gene expression values in linear form within an indexed and searchable database with a graphical interface recording quantitative levels of expression, expression variability and cross‑tissue width of expression for more than 31,000 transcripts. The present study conducted a meta‑analysis of a pool of 646 expression profile data sets from 54 different human tissues and identified actin γ 1 as the HK gene that best fits the combination of all the traditional criteria to be used as a reference gene for general use; two ribosomal protein genes, RPS18 and RPS27, and one aquaporin gene, POM121 transmembrane nucleporin C, were also identified. The present study provided a list of tissue‑ and organ‑specific genes that may be most suited for the following individual tissues/organs: Adipose tissue, bone marrow, brain, heart, kidney, liver, lung, ovary, skeletal muscle and testis; and also provides in these cases a representative, quantitative portrait of the relative, typical gene‑expression profile in the form of searchable database tables.

Project description:PURPOSE: To identify non-housekeeping genes definitively expressed in the human trabecular meshwork (TM). METHODS: Microarray gene expression data on TM cultured cells from four studies were compared. Genes that were queried in at least three studies and assessed to be expressed in at least three studies were considered definitively expressed genes of the human TM. Housekeeping genes were removed from this set of genes. The non-housekeeping TM gene profile was analyzed for pathway enrichment and microRNA targeting, using bioinformatics tools. The results were compared with results of previous non-array based studies. RESULTS: Nine hundred and sixty-two genes were identified as non-housekeeping TM expressed genes. Analysis of these by Kyoto Encyclopedia of Genes and Genomes led to identification of two enriched biologic pathways that achieved a highly significant Bonferroni p-value (p?0.01): focal adhesion and extracellular matrix (ECM)-receptor interaction. Many of the genes were previously implicated in TM-related functions and the TM-associated disease glaucoma; however, some are novel. MicroRNAs known to be expressed in the trabecular meshwork were predicted to target some of the genes. Ten genes identified here, ALDH1A1 (aldehyde dehydrogenase 1 family, member A1), CDH11 (cadherin 11, type 2, OB-cadherin), CXCR7 (chemokine (C-X-C motif) receptor 7), CHI3L1 (chitinase 3-like 1), FGF2 (fibroblast growth factor 2), GNG11 (guanine nucleotide binding protein [G protein], gamma 11), IGFBP5 (insulin-like growth factor binding protein 5), PTPRM (protein tyrosine phosphatase, receptor type, M), RGS5 (regulator of G-protein signaling 5), and TUSC3 (tumor suppressor candidate 3), were also reported as TM expressed genes in three earlier non-microarray based studies. CONCLUSIONS: A transcriptome consisting of 962 non-housekeeping genes definitively expressed in the human TM was identified. Multiple genes and microRNAs are proposed for further study for a better understanding of TM physiology.

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Preservation of ranking order in the expression of human Housekeeping genes.

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Preservation of ranking order in the expression of human Housekeeping genes.

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