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pmid:39433868

Landscape of the immune infiltration and identification of molecular diagnostic markers associated with immune cells in patients with kidney transplantation.

Zhangxiao Xu · Xun Sun · Xiaobo Ma · Bo Tao · Jian Wu · Yunpeng He · Yuan Zhao · Hexiang Mao · Jie Yang · Dehui Jiang · Lijun Wang · Chao Song

Scientific reports · 2024 doi:10.1038/s41598-024-75052-6

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Experiment

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Data

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title
Landscape of the immune infiltration and identification of molecular diagnostic markers associated with immune cells in patients with kidney transplantation.
doi
10.1038/s41598-024-75052-6
pmid
39433868
authors array · 12 items
[0]
Zhangxiao Xu
[1]
Xun Sun
[2]
Xiaobo Ma
[3]
Bo Tao
[4]
Jian Wu
[5]
Yunpeng He
[6]
Yuan Zhao
[7]
Hexiang Mao
[8]
Jie Yang
[9]
Dehui Jiang
[10]
Lijun Wang
[11]
Chao Song
journal
Scientific reports
year
2024
abstract
Rejection seriously affects the success of kidney transplantations. However, the molecular mechanisms underlying this rejection remain unclear. The GSE21374 and GSE36059 datasets were downloaded from the Gene Expression Omnibus (GEO) database. Next, the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm was used to infer the proportions of 22 immune cells. Moreover, infiltrating immune cell-related genes were identified using weighted gene co-expression network analysis (WGCNA), and enrichment analysis was conducted to observe their biological functions. Extreme Gradient Boosting (XGBoost) and Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression algorithms were used to screen hub genes. Quantitative real-time PCR was conducted to verify the number of immune cells and hub gene expression levels. The rejection and non-rejection groups showed significantly different distributions (P < 0.05) of eight immune cells (B cell memory, Plasma cells, mast cells, follicular helper T cells, T CD8 cells, Macrophages M1, T Cells CD4 memory activated, and gamma delta T cells). Subsequently, CD8A, CRTAM, GBP2, WARS, and VAMP5 were screened as hub genes using the XGBoost and LASSO algorithms and could be used as diagnostic biomarkers. Finally, differential analysis and quantitative real-time PCR suggested that CD8A, CRTAM, GBP2, WARS, and VAMP5 were upregulated in rejection samples compared to non-rejection samples. The present study identified five key infiltrating immune cell-related genes (CD8A, CRTAM, GBP2,WARS, and VAMP5) involved in kidney transplant rejection, which may explain the molecular mechanism of rejection in kidney transplantation development.
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To distinguish hub genes from prognostic genes, extreme gradient boosting (XGBoost)53 and least absolute shrinkage and selection operator (LASSO) logistic regression algorithms54 were applied to the GSE21374 dataset.
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To distinguish hub genes from prognostic genes, extreme gradient boosting (XGBoost)53 and least absolute shrinkage and selection operator (LASSO) logistic regression algorithms54 were applied to the GSE21374 dataset.
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The data analyzed in this study were obtained from public databases with the following relevant links: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21374, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE36059.
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The data analyzed in this study were obtained from public databases with the following relevant links: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21374, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE36059.
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Using the publicly downloaded GSE21374 and GSE36059 datasets, the study applied CIBERSORT, WGCNA, Kaplan–Meier survival analysis, XGBoost, and LASSO logistic regression to identify five diagnostic biomarkers—CD8A, CRTAM, GBP2, WARS, and VAMP5—that were upregulated in kidney transplant rejection samples.
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The GSE21374 and GSE36059 datasets were downloaded from the Gene Expression Omnibus (GEO) database.
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Extreme Gradient Boosting (XGBoost) and Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression algorithms were used to screen hub genes.
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Finally, by overlapping genes obtained by the XGBoost and LASSO algorithms, a total of five hub genes, including WARS, CD8A, CRTAM, GBP2, and VAMP5, were identified (Fig. 5G).
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sections[0] "Abstract" paragraph 1
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Finally, differential analysis and quantitative real-time PCR suggested that CD8A, CRTAM, GBP2, WARS, and VAMP5 were upregulated in rejection samples compared to non-rejection samples.
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Using the publicly downloaded GSE21374 and GSE36059 datasets, the study applied CIBERSORT, WGCNA, Kaplan–Meier survival analysis, XGBoost, and LASSO logistic regression to identify five diagnostic biomarkers—CD8A, CRTAM, GBP2, WARS, and VAMP5—that were upregulated in kidney transplant rejection samples.
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[217]
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[220]
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[221]
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[222]
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[223]
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[226]
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[228]
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[243]
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[246]
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[248]
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[250]
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[252]
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[259]
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[260]
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[278]
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[279]
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[284]
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[285]
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[288]
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[289]
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[290]
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[292]
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[293]
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[294]
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[295]
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[296]
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[299]
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[300]
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[303]
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[304]
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[318]
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[324]
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sample_count
411
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null
group_sizes_basis
null
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570
taxon
Homo sapiens
title
Molecular diagnosis of T cell-mediated rejection in human kidney transplant biopsies; Molecular diagnosis of antibody-mediated rejection in human kidney transplants
resolution_checked_at
2026-11-01T18:06:44Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
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false
licence_read
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[3] object · 15 fields
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data:geo:GSE36096
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https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE36096
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null
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null
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resolved
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null
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null
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The data analyzed in this study were obtained from public databases with the following relevant links: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21374, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE36059.
structure object · 15 fields
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GEO
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The data analyzed in this study were obtained from public databases with the following relevant links: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21374, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE36059.
access_statement_kind
data_availability_statement
sample_accessions array · 6 items
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sample_count
6
group_sizes
null
group_sizes_basis
null
platform
6246
taxon
Mus musculus
title
Gene expression profiling in BCR-ABL expressing LSCs and BCR-ABL-BLK expressing LSCs
resolution_checked_at
2026-11-01T20:16:08Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
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[0]
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[2]
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[3]
asset:data:geo:GSE36059 licence not read
[4]
asset:data:geo:GSE36096 not downloaded
[5]
asset:data:geo:GSE36096 licence not read
analysis object · 4 fields
state
partial
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[0] object · 10 fields
id
method-1
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machine_learning
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gradient_boosting
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train_classifier
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cross_validate
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roc_auc
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[0]
labelled_feature_matrix
evidence object · 3 fields
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quote
To distinguish hub genes from prognostic genes, extreme gradient boosting (XGBoost)53 and least absolute shrinkage and selection operator (LASSO) logistic regression algorithms54 were applied to the GSE21374 dataset.
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evidence object · 3 fields
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Wilcoxon
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method-3
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regression_modelling
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logistic
label
Regression modelling
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[0]
glm_logit_fit
missing_operations array · 0 items
parameters object · 0 fields
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[0]
predictors_and_outcome
evidence object · 3 fields
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0.7
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medium
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logistic regression
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gaps array · 1 item
[0]
method.reader_differs_from_extractor
capability object · 3 fields
state
complete
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[0] object · 6 fields
capability_id
capability:computational_analysis
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[0]
meta_analysis
[1]
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[7]
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[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
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readiness object · 8 fields
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complete
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R1
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nothing:replicable_now
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train_classifier
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roc_auc
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basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: gradient_boosting.
capability object · 4 fields
tier
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capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
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true
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[0]
GSE21374
[1]
GSE36059
[2]
GSE36096
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[0]
GSE21374
[1]
GSE36059
[2]
GSE36096
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[0]
The data analyzed in this study were obtained from public databases with the following relevant links: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21374, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE36059.
basis
The paper names GSE21374, GSE36059, GSE36096 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
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train_classifier
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[2]
roc_auc
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[0]
source:pmid:39433868
[1]
data:geo:GSE21374
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[0]
run_analysis
must_build object · 5 fields
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readers array · 0 items
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[0]
data:geo:GSE21374
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review object · 5 fields
state
partial
machine_critique object · 5 fields
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extraction_review
reader object · 5 fields
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MiniMax-M3.1-Flash
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minimax
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minimax
read_at
2026-11-01T19:36:18Z
independence
single_reader
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verbatim
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verbatim
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5
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10829
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264
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[0] object · 4 fields
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extraction
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MiniMax-M3.1-Flash
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minimax
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review.human_critique
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absent
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not_run
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execution.not_run
provenance object · 7 fields
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pmid:39433868
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paper
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pmid:39433868
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source:pmid:39433868
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PMID 39433868 full text
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data:geo:GSE21374
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dataset
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GEO GSE21374
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[0] object · 4 fields
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classification
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pmid:39433868
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PMID 39433868 full text
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dataset
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GEO GSE21374
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agent:corpus-assay-engine
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agent:minimax-reader
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lineage object · 4 fields
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[0]
were used to screen hub genes. Quantitative real-time PCR was conducted to verify the number of immune
[1]
ally, differential analysis and quantitative real-time PCR suggested that CD8A, CRTAM, GBP2, WARS, and
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paper_text_order:892
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assay:1
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machine_learning
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[0]
To distinguish hub genes from prognostic genes, extreme gradient boosting (XGBoost)53 and least absolute shrinkage and selection operator (LASSO) logistic regression algorithms54 were applied to the GSE21374 dataset.
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consumes_earlier_output
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39433868", "kind": "science-record", "revision": 4, "content_hash": "sha256:4b5079d80c0c6aa800e044e607c260bcdbdde4e8da93111a34856ec4251aed11", "created_at": "2026-11-01T20:29:41Z", "updated_at": "2026-11-01T22:55:28Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Landscape of the immune infiltration and identification of molecular diagnostic markers associated with immune cells in patients with kidney transplantation.", "doi": "10.1038/s41598-024-75052-6", "pmid": "39433868", "authors": ["Zhangxiao Xu", "Xun Sun", "Xiaobo Ma", "Bo Tao", "Jian Wu", "Yunpeng He", "Yuan Zhao", "Hexiang Mao", "Jie Yang", "Dehui Jiang", "Lijun Wang", "Chao Song"], "journal": "Scientific reports", "year": 2024, "abstract": "Rejection seriously affects the success of kidney transplantations. However, the molecular mechanisms underlying this rejection remain unclear. The GSE21374 and GSE36059 datasets were downloaded from the Gene Expression Omnibus (GEO) database. Next, the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm was used to infer the proportions of 22 immune cells. Moreover, infiltrating immune cell-related genes were identified using weighted gene co-expression network analysis (WGCNA), and enrichment analysis was conducted to observe their biological functions. Extreme Gradient Boosting (XGBoost) and Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression algorithms were used to screen hub genes. Quantitative real-time PCR was conducted to verify the number of immune cells and hub gene expression levels. The rejection and non-rejection groups showed significantly different distributions (P < 0.05) of eight immune cells (B cell memory, Plasma cells, mast cells, follicular helper T cells, T CD8 cells, Macrophages M1, T Cells CD4 memory activated, and gamma delta T cells). Subsequently, CD8A, CRTAM, GBP2, WARS, and VAMP5 were screened as hub genes using the XGBoost and LASSO algorithms and could be used as diagnostic biomarkers. Finally, differential analysis and quantitative real-time PCR suggested that CD8A, CRTAM, GBP2, WARS, and VAMP5 were upregulated in rejection samples compared to non-rejection samples. The present study identified five key infiltrating immune cell-related genes (CD8A, CRTAM, GBP2,WARS, and VAMP5) involved in kidney transplant rejection, which may explain the molecular mechanism of rejection in kidney transplantation development.", "claims": [{"id": "claim-method", "statement": "To distinguish hub genes from prognostic genes, extreme gradient boosting (XGBoost)53 and least absolute shrinkage and selection operator (LASSO) logistic regression algorithms54 were applied to the GSE21374 dataset.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39433868", "locator": "sections[20] \"Identification of hub genes by machine learning algorithms\" paragraph 2", "quote": "To distinguish hub genes from prognostic genes, extreme gradient boosting (XGBoost)53 and least absolute shrinkage and selection operator (LASSO) logistic regression algorithms54 were applied to the GSE21374 dataset."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data analyzed in this study were obtained from public databases with the following relevant links: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21374, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE36059.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39433868", "locator": "sections[32] \"notes\" paragraph 1", "quote": "The data analyzed in this study were obtained from public databases with the following relevant links: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21374, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE36059."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using the publicly downloaded GSE21374 and GSE36059 datasets, the study applied CIBERSORT, WGCNA, Kaplan–Meier survival analysis, XGBoost, and LASSO logistic regression to identify five diagnostic biomarkers—CD8A, CRTAM, GBP2, WARS, and VAMP5—that were upregulated in kidney transplant rejection samples.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39433868", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The GSE21374 and GSE36059 datasets were downloaded from the Gene Expression Omnibus (GEO) database."}, {"asset": "source:pmid:39433868", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Extreme Gradient Boosting (XGBoost) and Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression algorithms were used to screen hub genes."}, {"asset": "source:pmid:39433868", "locator": "sections[7] \"Identification of hub genes by machine learning algorithms\" paragraph 2", "quote": "Finally, by overlapping genes obtained by the XGBoost and LASSO algorithms, a total of five hub genes, including WARS, CD8A, CRTAM, GBP2, and VAMP5, were identified (Fig. 5G)."}, {"asset": "source:pmid:39433868", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Finally, differential analysis and quantitative real-time PCR suggested that CD8A, CRTAM, GBP2, WARS, and VAMP5 were upregulated in rejection samples compared to non-rejection samples."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using the publicly downloaded GSE21374 and GSE36059 datasets, the study applied CIBERSORT, WGCNA, Kaplan–Meier survival analysis, XGBoost, and LASSO logistic regression to identify five diagnostic biomarkers—CD8A, CRTAM, GBP2, WARS, and VAMP5—that were upregulated in kidney transplant rejection samples.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:39433868"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE21374"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE21374"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39433868", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1038/s41598-024-75052-6", "sha256": 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