Fluoxetine in H460 Lung Cancer
Multi-level analysis across 16 mechanisms reveals that fluoxetine's master transcriptomic program in H460 cells is SREBF1/2-driven lipid biosynthesis + MYC post-translational suppression. The original paper's ATF4-AKT-mTOR axis model is only partially supported - ATF4 acts post-translationally and is not a master transcriptional regulator.
Pharmacogenomic Drug Screen in Mouse Cerebrocortical Cultures
The original paper's all-sample z-score approach creates a ~4:1 upregulation bias that DESeq2 vehicle-only comparison reverses for many drugs. Only 50% directional agreement between methods across drugs with detectable DEGs in both — the single most impactful analytical decision in the pipeline.
ATG7 Deficiency Reshapes Microglia Biology in Alzheimer's Disease
Microglia-specific ATG7 deletion triggers a cascading failure across multiple biological systems. The primary mechanism is UPR impairment (especially the ATF6 arm), which creates a 'double vulnerability': cells simultaneously lose proteostasis protection AND gain ferroptotic susceptibility. In DAM cells, this manifests as a 'signaling desert' where 8 growth/survival pathways shut down, leaving only p53 and TNFa active — consistent with cells transitioning toward death rather than productive activation.
Atopic Dermatitis Transcriptome Under Dupilumab and Cyclosporine
Dupilumab and cyclosporine suppress distinct gene programs yet converge onto shared biological modules. A multi-level treatment hierarchy emerges from gene-level divergence (r = 0.56, only 6% gene overlap) to near-perfect module-level agreement (r = 0.95). This monotonic increase reveals that different gene targets feed into shared biological programs at progressively higher organizational levels.
IL-4, IL-13, and IL-33 Transcriptional Responses in Human Eosinophils and Mast Cells
IL-4, IL-13, and IL-33 activate largely non-overlapping transcriptional programs in human eosinophils and mast cells (>90% DEGs cell-type-specific, Spearman rho≈0). IL-33 drives the broadest response via NF-κB/AP-1 (NFKB1 as master regulator), including massive induction of IL-13 and IL-5 in mast cells — the very targets of downstream biologics.
Genome-wide Dissection of IL-33 and IL-4Rα Blockade in HDM-driven Airway Inflammation
Combination IL-33/IL-4Rα blockade yields 2,924 DEGs versus 284 from monotherapy sum (262 + 22), with 91.4% unique genes — unlocking an entirely distinct transcriptomic program rather than amplifying monotherapy effects.
How Genetic Ancestry Shapes Breast Cancer Biology
Genetic ancestry shapes breast cancer biology across transcriptomic (11,424 DEGs), immune (Th2 most robust, TReg challenged), pathway (78 enriched, IFNa top novel), genomic (CNA-driven, not mutation-driven), and prognostic (98.8% non-overlapping signatures) layers — but the total survival effect is null after adjusting for subtype, age, and stage.