Coupling of MAPK output and lineage identity defines archetypal modes of TKI resistance in EGFR-mutant lung adenocarcinoma

Rendered analysis notebooks for:

Zatzman, M., Quintanal-Villalonga, A. et al, Coupling of MAPK output and lineage identity defines archetypal modes of TKI resistance in EGFR-mutant lung adenocarcinoma.

Overview

One notebook per main figure, each carrying the supplementary figures its legend points to, executed end to end against the deposited data. Code is folded by default — open any block to see what produced the panel above it.

Source, setup instructions, and the processing notebooks that document how the deposited objects were built are in the code repository: https://github.com/shahcompbio/egfr_nucseq.

Figure notebooks

In paper order:

figure notebook
Fig 1 — cohort and timeline 01_cohort_metadata
Fig S2 — MSK-IMPACT panel sequencing 31_impact_analysis
Fig 2, S3–S5 — phenotypic shifts 90_figure2
Fig 3, S6–S8 — LUAD deprogramming 91_figure3
Fig 4, S9 — MAPK coupling 92_figure4
Fig 4C–D, S7C, S9C — Lung Cancer Cell Atlas 33_luca_analysis
Fig S9D, S9G — published transformation cohorts 34_bulk_transformation
Fig 5, S10 — lineage plasticity 93_figure5
Fig 6, S11–S13 — Xenium spatial cohort xenium/99_xenium_plots

Data

deposit holds
GEO GSE292469 — single-nucleus RNA-seq FASTQs and raw per-library count matrices for all 74 sequencing libraries, plus Series-level GSE292469_counts.h5 and GSE292469_cell_metadata.tsv.gz
GEO GSE342824 — Xenium in situ per-section XeniumRanger output for all ten sections — counts, cell and nucleus boundaries, decoded transcripts, morphology images — plus xenium_cell_metadata.tsv.gz and the 389-target gene_panel.json
Zenodo — DOI at publication the figure-reproduction bundle these notebooks run off: the three single-nucleus Seurat objects, the Xenium spatial object, and the derived result tables the notebooks read
CELLxGENE — link at publication the cohort, epithelial and tumor histotime objects, for interactive browsing and download

Every notebook here reads only from the Zenodo bundle.