Structured Expression Dispersion as a Derived Projection of Latent Biological Axes: A Mechanistic Reinterpretation of Survival Signals in TCGA Glioblastoma (v4.0)
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| Format: | Recurso digital |
| Sprache: | Englisch |
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2026
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| _version_ | 1866901412930125824 |
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| author | Mitchell , Thomas S. |
| author_facet | Mitchell , Thomas S. |
| contents | <p>This study evaluates whether gene expression dispersion (coefficient of variation, CV) represents a true survival signal or a projection artifact in high-dimensional transcriptomic data. In TCGA glioblastoma, CV stratifies survival; however, falsification through random gene controls, permutation testing, and cross-cancer analysis demonstrates that the signal is not robust or generalizable. Principal component analysis (PCA) substantially outperforms CV in survival prediction, and CV becomes non-significant when PCA is included. Correlation analysis shows that CV partially overlaps with latent structure, indicating that it represents a degraded projection. Enrichment analysis identifies a biologically coherent axis separating metabolic transport processes from extracellular matrix and angiogenic remodeling. These findings demonstrate that dispersion-based survival signals arise from structured biological programs rather than independent statistical mechanisms.</p> |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_5281_zenodo_19968131 |
| institution | Zenodo |
| language | eng |
| publishDate | 2026 |
| publisher | Zenodo |
| record_format | zenodo |
| spellingShingle | Structured Expression Dispersion as a Derived Projection of Latent Biological Axes: A Mechanistic Reinterpretation of Survival Signals in TCGA Glioblastoma (v4.0) Mitchell , Thomas S. Glioblastoma, TCGA, gene expression, coefficient of variation, PCA, survival analysis, latent structure, high-dimensional biology, tumor microenvironment, angiogenesis <p>This study evaluates whether gene expression dispersion (coefficient of variation, CV) represents a true survival signal or a projection artifact in high-dimensional transcriptomic data. In TCGA glioblastoma, CV stratifies survival; however, falsification through random gene controls, permutation testing, and cross-cancer analysis demonstrates that the signal is not robust or generalizable. Principal component analysis (PCA) substantially outperforms CV in survival prediction, and CV becomes non-significant when PCA is included. Correlation analysis shows that CV partially overlaps with latent structure, indicating that it represents a degraded projection. Enrichment analysis identifies a biologically coherent axis separating metabolic transport processes from extracellular matrix and angiogenic remodeling. These findings demonstrate that dispersion-based survival signals arise from structured biological programs rather than independent statistical mechanisms.</p> |
| title | Structured Expression Dispersion as a Derived Projection of Latent Biological Axes: A Mechanistic Reinterpretation of Survival Signals in TCGA Glioblastoma (v4.0) |
| topic | Glioblastoma, TCGA, gene expression, coefficient of variation, PCA, survival analysis, latent structure, high-dimensional biology, tumor microenvironment, angiogenesis |
| url | https://doi.org/10.5281/zenodo.19968131 |