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bioRxiv · 10.64898/2026.08.30.748149

Integrated Transcriptomic and CRISPR Dependency Analysis Prioritizes a CDK1-AURKB Mitotic Vulnerability Axis in Diffuse Intrinsic Pontine Glioma

Rajeev, A.·Veeragoni, S.·Sundar, A.
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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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Rajeev, A., Veeragoni, S., Sundar, A.. 2026-09-01. Integrated Transcriptomic and CRISPR Dependency Analysis Prioritizes a CDK1-AURKB Mitotic Vulnerability Axis in Diffuse Intrinsic Pontine Glioma. https://doi.org/10.64898/2026.08.30.748149

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