Salvato in:
| Autori principali: | , |
|---|---|
| Natura: | Recurso digital |
| Lingua: | inglese |
| Pubblicazione: |
Zenodo
2026
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| Soggetti: | |
| Accesso online: | https://doi.org/10.5281/zenodo.19737247 |
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Sommario:
- <h2><span>Abstract</span></h2> <p><span>We report the results of a pre-registered confirmatory analysis (OSF osf.io/C6u3t) that failed. The hypothesis — that mesoscale spatial autocorrelation (ρ_meso) would be consistently higher in tumour tissue than matched normal tissue across four signalling channels in NSCLC — was not confirmed at the pre-registered significance threshold across the full 7-patient cohort from E-MTAB-13530.</span></p> <p> </p> <p><span>The pre-registered verdict is </span><span>failure to replicate</span><span> (0/4 channels reaching Bonferroni-corrected significance for ρ_meso; 4/7 patients showing ≥3/4 channels with tumour > normal).</span></p> <p> </p> <p><span>However, the data reveal three findings that survive the failed hypothesis. First, the proliferation channel shows unanimously higher spatial autocorrelation in tumour tissue (7/7 patients, Global Moran's I p=0.0078 — reaching Bonferroni-corrected significance in this cohort, subject to the UMI depth limitation noted below), suggesting that proliferative fronts create detectable mesoscale gradients absent in normal lung. Second, the four signalling channels behave differently in biologically interpretable ways: immune and proliferation channels consistently show tumour > normal, while EMT and hypoxia do not. Third, the two patients (P17, P24) who deviate most strongly from the majority pattern are clinically distinct — P17 is the only histologically unclassifiable (NSCLC-NOS) patient with the smallest tumour, and P24 is the youngest patient in the cohort. These observations generate testable hypotheses about the relationship between histological subtype, tumour size, molecular driver, and spatial organisation, but they do not confirm any framework prediction. The outlier analysis is post-hoc and hypothesis-generating, not confirmatory.</span></p> <p> </p> <p><span>The scale mismatch finding from SIP-ONC-01A is replicated: standard-resolution spatial transcriptomics (Visium, 55 μm) measures pathophysiological organisation, not developmental coordination, across the full cohort.</span></p>