Genome-Wide Analysis of a Wnt1-Regulated Transcriptional Network Implicates Neurodegenerative Pathways

Eric M. Wexler,* Ezra Rosen, Daning Lu, Gregory E. Osborn, Elizabeth Martin, Helen Raybould, Daniel H. Geschwind

*To whom correspondence should be addressed. E-mail: ewexler{at}ucla.edu

This PDF file includes:

• Methods
• References
• Fig. S1. Wnt1 differentially modulates Wnt pathway genes across time.
• Fig. S2. Wnt1 induces significant early enrichment of genes involved in survival signaling, energy metabolism, and biosynthesis (anabolism).
• Fig. S3. Wnt1 induces significant later enrichment of genes involved in blood vessel development, axonogenesis, and Huntington's disease.
• Fig. S4. Dynamic time warping (DTW) sensitivity analysis of simulated expression data.
• Fig. S5. DTW sensitivity analysis of experimental data.
• Fig. S6. DTW identifies Wnt1 effects on cancer-related genes.
• Fig. S7. Demonstration of robust blind source separation using parallel independent component analysis (pICA).
• Fig. S8. Overview of mutual information–based network inference and sensitivity to thresholding effects.
• Fig. S9. Scalable version of Fig. 2: Wnt1 modulates genes implicated in Wnt signaling and Alzheimer's disease (AD).
• Fig. S10. Scalable version of Fig. 3: Unsupervised pICA blindly separates gene expression patterns by biological function.
• Fig. S11. Scalable version of Fig. 4: Combined topological overlap–based clustering and dynamic Bayesian network construction links Wnt1 signaling with changes in dementia-related genes.
• Fig. S12. Scalable version of Fig. 5: Wnt1 induces a gene expression architecture that correlates many well-known dementia genes with Wnt-related signal transduction.

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Other Supplementary Material for this manuscript includes the following:

• Table S1 (Microsoft Excel format). Overlap of gene changes across time.
• Table S2 (Microsoft Excel format). Wnt1-induced immediate changes in known Wnt-related genes.
• Table S3 (Microsoft Excel format). Wnt1-mediated enrichment of GO and KEGG pathways varies across epochs.
• Table S4 (Microsoft Excel format). Wnt-1 induces changes in genes implicated in AD by genetic association studies.
• Table S5 (Microsoft Excel format). GO analysis of whole time series DTW-identified genes.
• Table S6 (Microsoft Excel format). Extended ICA gene list and ontology analysis table.
• Table S7 (Microsoft Excel format). ICA-GO sensitivity analysis.
• Table S8 (Microsoft Excel format). Gene Set Enrichment Analysis of ICA module genes probed against the Broad Institute's Molecular Signatures Database (MSigDB).
• Table S9 (Microsoft Excel format). Unique, independent statistical analyses identify similar Wnt1-mediated changes in gene expression.

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© 2011 American Association for the Advancement of Science