Evidence map›Paper›PMID 42749447›Full record

ArticleJournal, genetic engineering & biotechnology2026

Explainable machine learning and multimodal single cell analysis link NR4A2 to CD8

Shah Faisal, Abdul Sammad, Muhammad Adeel Ejaz, Zhen-Bo Wang

Abstract read
In one paragraph

Article in Journal, genetic engineering & biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Shah FaisalCenter for Cell Lineage Technology and Engineering, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: shahfaisal11495@gmail.com.
Abdul SammadDepartment of General Practice, The Fifth Affiliated Hospital of Southern Medical University, Guangzhou 510900, China.
Muhammad Adeel EjazCenter for Cell Lineage Technology and Engineering, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Zhen-Bo WangDepartment of General Practice, The Fifth Affiliated Hospital of Southern Medical University, Guangzhou 510900, China. Electronic address: wzboy2172@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTerminal exhaustion of CD8

methodsWe reanalysed publicly available human HCC datasets spanning four modalities: single-cell RNA sequencing (scRNA-seq; GSE149614, GSE98638, GSE151530, GSE125449), single-cell ATAC sequencing (scATAC-seq; GSE227265), imaging-based spatial transcriptomics (10× Xenium human liver-cancer section) and bulk RNA sequencing with overall-survival annotation (TCGA-LIHC). NR4A2 was profiled across cell compartments and, at higher resolution, across CD8

resultsNR4A2 was broadly expressed across HCC compartments and was highest in myeloid cells rather than being T-cell restricted; at whole-compartment and bulk-tumour resolution it was not a clean exhaustion marker. At the resolution of CD8

conclusionsA NR4A2 co-expression regulon was most active in exhausted cells; explainable modelling linked NR4A2-high status to an immediate-early/AP-1 activation programme; the programme marked immune-hot tumours; and although bulk NR4A2 was non-prognostic, a CD8-infiltration-adjusted exhaustion score was independently associated with worse overall survival (HR 1.42 per SD, p < 0.001). Across four independent data modalities, NR4A2 behaves as a resolution-dependent marker of the terminal-exhaustion programme in HCC CD8

Indexed as

CD8(+) T-cell exhaustionExplainable machine learning (SHAP)Hepatocellular carcinomaImmune checkpoint blockadeNR4A2Prognostic signatureSingle-cell RNA sequencingSpatial transcriptomicsTumour microenvironment

Identifiers

PMID42749447
PMCPMC13427649

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.