Trajectory inference of epithelial-centered neighborhood profiles reconstructs a pseudo-temporal continuum in idiopathic pulmonary fibrosis
Abstract
Idiopathic pulmonary fibrosis (IPF) is characterized by complex lung architecture and spatially heterogeneous remodeling, which have hindered integrated analysis of cell-intrinsic activity and intercellular communication during disease progression. Here we profiled six IPF lung specimens comprising more than 630,000 cells using the Xenium 5k panel and developed an epithelial-centered neighborhood profiling framework based on the local cellular composition around each epithelial cell. This approach captured fibrosis-associated variation in epithelial niches without requiring predefined histological regions. Pseudo-temporal continuum inference of these profiles reconstructed a continuous axis that reflected the spatial progression of fibrotic remodeling from relatively preserved alveolar regions to fibrotic and airway-like remodeled regions. Within this spatial dataset, we mapped coordinated changes in epithelial states, local microenvironments, epithelial intracellular pathway activities, and directional interactions with neighboring cell types along the same axis. Our findings provide a spatial framework that generates testable hypotheses for progressive epithelial niche remodeling in IPF.
Full-text reasoning
From the deep-tier full-text analysis of this preprint.
Reasoning review — 5 key claims, 0 well-supported, 5 with gaps
- partial The Xenium dataset was effectively filtered to remove low-quality cells. gap: No data is presented to demonstrate the effectiveness or justification of the chosen filtering thresholds.
- partial Sample-level batch effects were successfully mitigated during data integration. gap: No data is presented to demonstrate the successful mitigation of batch effects (e.g., pre/post-integration visualizations or metrics).
- partial Reliable cell-type annotations were achieved, even for genes not in the Xenium panel, through a robust imputation strategy. gap: No validation or evidence of the accuracy of the imputed cell-type annotations is provided in the text.
- partial Transcriptional programs associated with inferred cell-cell interaction signals can be accurately assessed using their described methodology. gap: The methodology and validity of inferring the initial 'incoming interaction signals' are not described or supported.
- unsupported Immunofluorescence staining provided valid validation data for the study. gap: No validation data or results from immunofluorescence are presented in the text to support this claim.
Claims and gaps are read from the full text by a language model, shown for transparency; they do not affect ranking or selection.
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- biorxiv v1 2026-06-18 source ↗
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bioRxiv Bioinfo @biorxiv-bioinfo.bsky.social · 4920 followers neutral
Trajectory inference of epithelial-centered neighborhood profiles reconstructs a pseudo-temporal continuum in idiopathic pulmonary fibrosis https://www.biorxiv.org/content/10.64898/2026.06.15.732243v1
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bioRxivpreprint @biorxivpreprint.bsky.social · 8895 followers neutral
Trajectory inference of epithelial-centered neighborhood profiles reconstructs a pseudo-temporal continuum in idiopathic pulmonary fibrosis https://www.biorxiv.org/content/10.64898/2026.06.15.732243v1