Functional categories associated with clusters of genes that are co-expressed across the NCI-60 cancer cell lines
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Published on: October 11, 2019
Barry R Zeeberg1, William Reinhold, René Snajder
1Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America. zeebergb@mail.nih.gov
Background:
The NCI-60 is a panel of 60 diverse human cancer cell lines used by the U.S. National Cancer Institute to screen compounds for anticancer activity. In the current study, gene expression levels from five platforms were integrated to yield a single composite transcriptome profile. The comprehensive and reliable nature of that dataset allows us to study gene co-expression across cancer cell lines.
Methodology/Principal Findings:
Hierarchical clustering revealed numerous clusters of genes in which the genes co-vary across the NCI-60. To determine functional categorization associated with each cluster, we used the Gene Ontology (GO) Consortium database and the GoMiner tool. GO maps genes to hierarchically-organized biological process categories. GoMiner can leverage GO to perform ontological analyses of gene expression studies, generating a list of significant functional categories.
Conclusions/Significance:
GoMiner analysis revealed many clusters of coregulated genes that are associated with functional groupings of GO biological process categories. Notably, those categories arising from coherent co-expression groupings reflect cancer-related themes such as adhesion, cell migration, RNA splicing, immune response and signal transduction. Thus, these clusters demonstrate transcriptional coregulation of functionally-related genes.
Insights
This study integrated gene expression data from the NCI-60 cancer cell lines. GoMiner analysis revealed coregulated genes linked to cancer-related functions like cell migration and immune response.
Area of Science:
- Genomics
- Bioinformatics
- Cancer Biology
Background:
- The National Cancer Institute-60 (NCI-60) is a diverse panel of 60 human cancer cell lines.
- It is utilized for screening anticancer compounds.
- Gene expression data from five platforms were integrated into a composite transcriptome profile.
Purpose of the Study:
- To study gene co-expression patterns across the NCI-60 cancer cell lines.
- To identify functional categories associated with co-expressed genes.
Main Methods:
- Integrated gene expression data from five platforms to create a composite transcriptome profile.
- Applied hierarchical clustering to identify co-varying gene clusters.
- Utilized the Gene Ontology (GO) Consortium database and GoMiner tool for functional categorization.
Main Results:
- Hierarchical clustering identified numerous gene clusters exhibiting co-variation across the NCI-60 panel.
- GoMiner analysis revealed significant functional categories associated with these gene clusters.
- Identified cancer-related themes including adhesion, cell migration, RNA splicing, immune response, and signal transduction.
Conclusions:
- GoMiner analysis successfully identified clusters of coregulated genes linked to functional groupings within GO biological process categories.
- These findings demonstrate the transcriptional coregulation of functionally related genes.
- The identified clusters highlight key biological processes relevant to cancer progression and response.
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