{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T11:25:42Z","timestamp":1773055542135,"version":"3.50.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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.<\/jats:p><jats:p>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.<\/jats:p><jats:p>Availability: The software is available as Supplementary Material.<\/jats:p><jats:p>Contact: joseph.szustakowski@novartis.com<\/jats:p><jats:p>Supplementary information: Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btm116","type":"journal-article","created":{"date-parts":[[2007,3,29]],"date-time":"2007-03-29T00:32:41Z","timestamp":1175128361000},"page":"1356-1362","source":"Crossref","is-referenced-by-count":7,"title":["Extending the pathway analysis framework with a test for transcriptional variance implicates novel pathway modulation during myogenic differentiation"],"prefix":"10.1093","volume":"23","author":[{"given":"Daniel M.","family":"Kemp","sequence":"first","affiliation":[{"name":"1 Diabetes and Metabolism Disease Area and 2Genome and Proteome Sciences, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA 02139, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. 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