Single-cell geometry of drug responses across malignant glioma states

Response direction to drugs is highly coherent across malignant glioma transcriptional states, with C showing strong reproducibility (r=0.931) across 43 treatment–vehicle comparisons.

• Why it matters: Drug response is often reduced to a single score, masking whether AC-, OPC-, NPC-, and MES-like states shift together or diverge within the same tumor slice.
• What they did: A reanalysis of a public single-cell RNA-seq dataset of drug-treated glioma slice cultures (391,444 cells; 252,106 transformed cells) tested coherence (C) and state-separation change (K) across 43 comparisons from 19 TissueID-defined units.
• The result: C exceeded two null models in 41 of 43 comparisons and was positive in all 19 units (P=3.8e-6), while within-drug coherence surpassed between-drug coherence in all 52 drug pairs (P=0.000488).

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