Integrated Transcriptomic and CRISPR Dependency Analysis Prioritizes a CDK1-AURKB Mitotic Vulnerability Axis in Diffuse Intrinsic Pontine Glioma
- 1Austin Community College
Abstract
Diffuse intrinsic pontine glioma (DIPG), now classified within diffuse midline glioma, H3K27-altered, remains a lethal pediatric brainstem tumor with limited therapeutic options. Here, we integrated public DIPG transcriptomic datasets, protein-protein interaction modeling, functional enrichment, immune deconvolution, survival analysis, and DepMap CRISPR dependency data to nominate candidate mitotic vulnerabilities. Differential expression analysis comparing 27 DIPG tumors with 6 brainstem low-grade glioma comparator samples identified a proliferative transcriptional program enriched for chromosome segregation, nuclear division, and cell-cycle pathways. Network analysis prioritized a compact mitotic hub module containing CDK1, AURKB, TOP2A, CDC20, CDCA8, and related G2/M regulators. CIBERSORT analysis of an independent DIPG cohort inferred low cytotoxic T-cell signal, consistent with an immune-cold phenotype, although immune-cell fractions require orthogonal validation. Survival analysis showed that neither inferred immune scores nor a composite mitotic hub score significantly stratified overall survival. DepMap CRISPR gene-effect data nominated CDK1, AURKB, TOP2A, and BIRC5 as candidate dependencies across brain tumor models. These findings provide a computational framework for prioritizing mitotic vulnerabilities in DIPG and support experimental validation in disease-relevant models.
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BibTeX
@misc{rajeev2026integrated,
title = {{Integrated Transcriptomic and CRISPR Dependency Analysis Prioritizes a CDK1-AURKB Mitotic Vulnerability Axis in Diffuse Intrinsic Pontine Glioma}},
author = {A. Rajeev and S. Veeragoni and A. Sundar},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.30.748149},
url = {https://www.biorxiv.org/content/10.64898/2026.08.30.748149v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Integrated Transcriptomic and CRISPR Dependency Analysis Prioritizes a CDK1-AURKB Mitotic Vulnerability Axis in Diffuse Intrinsic Pontine Glioma
AU - A. Rajeev
AU - S. Veeragoni
AU - A. Sundar
PY - 2026
DA - 2026/08/30
PB - bioRxiv
DO - 10.64898/2026.08.30.748149
UR - https://www.biorxiv.org/content/10.64898/2026.08.30.748149v1
AB - Diffuse intrinsic pontine glioma (DIPG), now classified within diffuse midline glioma, H3K27-altered, remains a lethal pediatric brainstem tumor with limited therapeutic options. Here, we integrated public DIPG transcriptomic datasets, protein-protein interaction modeling, functional enrichment, immune deconvolution, survival analysis, and DepMap CRISPR dependency data to nominate candidate mitotic vulnerabilities. Differential expression analysis comparing 27 DIPG tumors with 6 brainstem low-grade glioma comparator samples identified a proliferative transcriptional program enriched for chromosome segregation, nuclear division, and cell-cycle pathways. Network analysis prioritized a compact mitotic hub module containing CDK1, AURKB, TOP2A, CDC20, CDCA8, and related G2/M regulators. CIBERSORT analysis of an independent DIPG cohort inferred low cytotoxic T-cell signal, consistent with an immune-cold phenotype, although immune-cell fractions require orthogonal validation. Survival analysis showed that neither inferred immune scores nor a composite mitotic hub score significantly stratified overall survival. DepMap CRISPR gene-effect data nominated CDK1, AURKB, TOP2A, and BIRC5 as candidate dependencies across brain tumor models. These findings provide a computational framework for prioritizing mitotic vulnerabilities in DIPG and support experimental validation in disease-relevant models.
ER -