Related Experiment Video
Updated: Jul 16, 2026

Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
Published on: June 21, 2016
Extending the pathway analysis framework with a test for transcriptional variance implicates novel pathway modulation
Daniel M Kemp1, N R Nirmala, Joseph D Szustakowski
1Diabetes and Metabolism Disease Area, Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
Motivation:
We describe an extension of the pathway-based enrichment approach for analyzing microarray data via a robust test for transcriptional variance. The use of a variance test is intended to identify additional patterns of transcriptional regulation in which many genes in a pathway are up- and down-regulated. Such patterns may be indicative of the reciprocal regulation of pathway activators and inhibitors or of the differential regulation of separate biological sub-processes and should extend the number of detectable patterns of transcriptional modulation.
Results:
We validated this new statistical approach on a microarray experiment that captures the temporal transcriptional profile of muscle differentiation in mouse C2C12 cells. Comparisons of the transcriptional state of myoblasts and differentiated myotubes via a robust variance test implicated several novel pathways in muscle cell differentiation previously overlooked by a standard enrichment analysis. Specifically, pathways involved in cell structure, calcium-mediated signaling and muscle-specific signaling were identified as differentially modulated based on their increased transcriptional variance. These biologically relevant results validate this approach and demonstrate the flexible nature of pathway-based methods of data analysis.
Availability:
The software is available as Supplementary Material.
More Related Videos
08:51Applying an Inducible Expression System to Study Interference of Bacterial Virulence Factors with Intracellular Signaling
Published on: June 25, 2015
12:54Real-time Analysis of Transcription Factor Binding, Transcription, Translation, and Turnover to Display Global Events During Cellular Activation
Published on: March 7, 2018
Related Concept Videos
Master Transcription Regulators
Regulation of Expression at Multiple Steps
Diversity in Cell Signaling Responses
Graded and Abrupt Responses
Some signaling systems generate...
Regulation of Expression Occurs at Multiple Steps
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Regulation of Expression Occurs at Multiple Steps
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...