ArticleFrontiers in cell and developmental biology2026
Multi-omics mapping of PSC genetic risk to a high TWAS-active JAML+ lipid-associated macrophage program: bridging single-cell heterogeneity, spatial fibrotic niches, and machine learning selection.
Article in Frontiers in cell and developmental biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease with progressive peribiliary inflammation and fibrosis. Disease-modifying therapies are lacking, and the cell-type-specific mechanisms linking genetic susceptibility to pathogenic immune states remain incompletely understood. Methods: We performed a transcriptome-wide association study (TWAS) using PSC GWAS summary statistics and GTEx v8 liver eQTL weights. TWAS-prioritized genes were mapped onto a PSC liver single-cell RNA-seq atlas (GSE247128) using integrated gene set scoring (irGSEA). Monocyte/macrophage subsets were re-clustered and lipid-associated macrophages (LAMs) were stratified by TWAS activity. Core genes distinguishing high-versus low-activity LAMs were identified using seven machine-learning feature selection algorithms. JAML was validated in bulk transcriptomic cohorts (GSE119600, GSE177044), evaluated by immune infiltration analysis, examined by cell-cell communication inference (CellChat), assessed by virtual knockout (scTenifoldKnk), and spatially localized using Visium FFPE spatial transcriptomics (PSC: GSE245620; control: GSE240429), and validated at the protein level using Western blot and ELISA in an Results: TWAS activity was predominantly enriched in the monocyte/macrophage lineage. Within this lineage, LAMs (TREM2+ GPNMB+ APOC1+) showed the highest TWAS activity and occupied late pseudotime states. High-activity LAMs were enriched in fibrosis-related pathways (e.g., TGF-β, NOTCH, WNT/β-catenin) and innate immune pathways (e.g., TLR2/4-MAPK, NLRP3 inflammasome). Multi-algorithm feature selection identified JAML (AMICA1) as a core discriminator of high-versus low-activity LAMs. JAML was upregulated in PSC in bulk cohorts, associated with higher macrophage and lower activated CD8 Conclusion: Integrating TWAS with single-cell and spatial transcriptomics highlights a genetically linked, highly active LAM state in PSC and nominates JAML + LAMs as a testable effector population potentially connecting genetic susceptibility to peribiliary fibrosis, with
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.