Identification of interactive gene networks: A novel approach in gene array profiling of myometrial events during guinea pig pregnancy

doi:10.1016/j.ajog.2005.12.044

American Journal of Obstetrics and Gynecology

Volume 194, Issue 6, June 2006, Pages 1513-1523

https://doi.org/10.1016/j.ajog.2005.12.044 Get rights and content

Objective

The transition from myometrial quiescence to activation is poorly understood, and the analysis of array data is limited by the available data mining tools. We applied functional analysis and logical operations along regulatory gene networks to identify molecular processes and pathways underlying quiescence and activation.

Study design

We analyzed some 18,400 transcripts and variants in guinea pig myometrium at stages corresponding to quiescence and activation, and compared them to the nonpregnant (control) counterpart using a functional mapping tool, MetaCore (GeneGo, St Joseph, MI) to identify novel gene networks composed of biological pathways during mid (MP) and late (LP) pregnancy.

Results

Genes altered during quiescence and or activation were identified following gene specific comparisons with myometrium from nonpregnant animals, and then linked to curated pathways and formulated networks. The MP and LP networks were subtracted from each other to identify unique genomic events during those periods. For example, changes 2-fold or greater in genes mediating protein biosynthesis, programmed cell death, microtubule polymerization, and microtubule based movement were noted during the transition to LP.

Conclusion

We describe a novel approach combining microarrays and genetic data to identify networks associated with normal myometrial events. The resulting insights help identify potential biomarkers and permit future targeted investigations of these pathways or networks to confirm or refute their importance.

Section snippets

Tissue preparation

This protocol was approved by the Animal Use Committee at the University of Maryland. Guinea pigs obtained from commercial breeders were sacrificed and the myometrium harvested from the contraplacental wall of midpregnant (MP, 0.67 gestation, quiescent myometrium, n = 3), late pregnant (LP, 0.96 gestation, active myometrium, n = 3), and nonpregnant (NP, n = 3) guinea pigs. The tissue was first washed in phosphate-buffered saline (PBS) and then immediately frozen in liquid nitrogen and stored at

Gene expression profiles of guinea pig myometrium during mid and late gestation

Complete listing and categorization of all genes up- and down-regulated by a least a factor of 2 during MP and LP are provided in Table I, Table II. A cursory review of the findings reveals a greater distribution of genes significantly altered during LP than MP when both are compared with NP. Moreover, a higher number of genes appear to be up-regulated than down-regulated at MP, whereas at LP there appears to be more down-regulation than up-regulation.

Only 6% of the probe set IDs corresponding

Comment

We applied a 2-tiered approach to microarray analysis to move outside the traditional but introspective cluster analysis approach. First, we used conventional gene array technology to screen and identify target genes and gene products that were temporally regulated in the myometrium during pregnancy. Second, we generated ‘functional gene networks’ using Metacore™ to integrate reactions and interactions around the identified genes of interest. The result is a global and comprehensive analysis of

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It includes a curated database of human protein interactions and metabolism; hence, it is useful for analyzing a cluster of genes in the context of regulatory networks and signaling pathways. For the network analysis of a group of genes, MetaCore can be used to calculate the statistical significance (p value) based on the probability of assembly from a random set of nodes (genes) of the same size as the input list [19]. Maternal ages in the CS group were greater than those in the preeclampsia group.
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: Supported by the following grants from the United States Public Health Service: HL49041 (C.P.W.), U01-DP000187 (C.P.W.), and HD049185 (C.P.W.).

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Editors' ChoiceIdentification of interactive gene networks: A novel approach in gene array profiling of myometrial events during guinea pig pregnancy

Objective

Study design

Results

Conclusion

Section snippets

Tissue preparation

Gene expression profiles of guinea pig myometrium during mid and late gestation

Comment

Trends Pharmacol Sci

Toxicol Lett

J Biol Chem

Biochim Biophys Acta

Cell Calcium

Biochem Biophys Res Commun

J Biol Chem

Mutat Res

Curr Opin Cell Biol

Obstet Gynecol

J Steroid Biochem Mol Biol

Myometrial maturation and labour

Ann Med

The control of labor

N Engl J Med

Mechansims of labour-biochemical aspects

BJOG

Human myometrial gene expression before and during parturition

Biol Reprod

A functional genomic study to identify differential gene expression in the preterm and term human myometrium

Biol Reprod

Microarray analysis of uterine gene expression in mouse and human pregnancy

Mol Endocrinol

Application of a functional genomics approach to identify differentially expressed genes in human myometrium during pregnancy and labour

Mol Hum Reprod

Editors' Choice
Identification of interactive gene networks: A novel approach in gene array profiling of myometrial events during guinea pig pregnancy