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pmid:32048448

STAT1 and its related molecules as potential biomarkers in Mycobacterium tuberculosis infection.

Xing-Hao Yi · Bo Zhang · Yu-Rong Fu · Zheng-Jun Yi

Journal of cellular and molecular medicine · 2020 doi:10.1111/jcmm.14856

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complete

Experiment

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Data

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Analysis

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title
STAT1 and its related molecules as potential biomarkers in Mycobacterium tuberculosis infection.
doi
10.1111/jcmm.14856
pmid
32048448
authors array · 4 items
[0]
Xing-Hao Yi
[1]
Bo Zhang
[2]
Yu-Rong Fu
[3]
Zheng-Jun Yi
journal
Journal of cellular and molecular medicine
year
2020
abstract
Tuberculosis (TB) is a severe infectious disease that seriously endangers human health. The immune defence mechanism of the body against TB is still unclear. The purpose of this study was to find the key molecules involved in the immune defence response during TB infection, and provide reference for the treatment of TB and further understanding of the immune defence mechanism of the body. Data from GSE83456 were downloaded from GEO data sets for analysis, and a total of 192 differentially expressed genes were screened out. Most of these genes are enriched in the interferon signalling pathway and are defence response-related. We also found that STAT1 plays an important role in the immune defence of TB infection and it is one of the key genes related to interferon signalling pathway. STAT1-related molecules including hsa-miR-448, hsa-miR-223-3p, SAMD8_hsa_circRNA 994 and TWF1_hsa_circRNA 9897 were therefore screened out. Furthermore, expression levels of hsa-miR-448 and hsa-miR-223-3p were then verified by qRT-PCR. Results showed that both hsa-miR-448 and hsa-miR-223-3p were down-regulated in plasma from patients with pulmonary TB. Taken together, our data indicate that an mRNA-miRNA-circRNA interaction chain may play an important role in the infection of MTB, and STAT1 and related molecules including hsa-miR-223-3p, has-miR-448, SAMD8_hsa_circRNA994 and TWF1_hsa_circRNA9897 were identified as potential biomarkers in the development of active TB.
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The original expression matrix was normalized and processed by R. The limma package was used to screen out differentially expressed genes. The P‐value of genes was calculated using t test method, and Benjamini and Hochberg's method was used to calculate the adjusted P‐value. The clinical samples of TB infection were retrieved from the GEO database. A total of 106 blood samples were selected from http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE83456, including 45 pulmonary tuberculosis (PTB) samples and 61 healthy control (HC) samples.
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The limma package was used to screen out differentially expressed genes.
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The P‐value of genes was calculated using t test method, and Benjamini and Hochberg's method was used to calculate the adjusted P‐value.
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sections[3] "Acquisition of RNA information" paragraph 2
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The clinical samples of TB infection were retrieved from the GEO database.
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sections[3] "Acquisition of RNA information" paragraph 2
quote
A total of 106 blood samples were selected from http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE83456, including 45 pulmonary tuberculosis (PTB) samples and 61 healthy control (HC) samples.
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Construction of protein‐protein interaction (PPI) network and further excavation of gene clusters involved in immune system–related biological pathway
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miR‐181a‐2‐3p
[1]
STATl, OAS3
[2]
2
locator
section[14]/table-wrap[1]#jcmm14856-tbl-0004
gaps array · 2 items
[0]
asset:data:geo:GSE83456 not downloaded
[1]
asset:data:geo:GSE83456 licence not read
analysis object · 4 fields
state
complete
methods array · 2 items
[0] object · 10 fields
id
method-1
family
differential_expression
specific
limma_voom
label
Differential expression analysis
dsl_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
missing_operations array · 0 items
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[0]
count_matrix_with_condition
evidence object · 3 fields
score
1
band
reordered
quote
The original expression matrix was normalized and processed by R. The limma package was used to screen out differentially expressed genes. The P‐value of genes was calculated using t test method, and Benjamini and Hochberg's method was used to calculate the adjusted P‐value. The clinical samples of TB infection were retrieved from the GEO database. A total of 106 blood samples were selected from http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE83456, including 45 pulmonary tuberculosis (PTB) samples and 61 healthy control (HC) samples.
[1] object · 10 fields
id
method-2
family
network_analysis
specific
pathway_enrichment
label
Network / pathway analysis
dsl_operations array · 1 item
[0]
pathway_enrich
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
edge_list
evidence object · 3 fields
score
0.8
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high
quote
pathway enrichment
targets array · 0 items
gaps array · 0 items
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
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true
required_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
missing_operations array · 0 items
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom.
capability object · 4 fields
tier
R1
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
reachable
true
accessions array · 1 item
[0]
GSE83456
resolved_accessions array · 1 item
[0]
GSE83456
statements array · 1 item
[0]
Data sets used and analysed during the current study are available from the corresponding author on reasonable request.
basis
The paper names GSE83456 in NCBI 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
dsl_operations array · 3 items
[0]
normalise_counts
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differential_expression_fit
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fdr_bh
assets array · 6 items
[0]
source:pmid:32048448
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data:geo:GSE83456
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asset:table:pmid:32048448:1
[3]
asset:table:pmid:32048448:2
[4]
asset:table:pmid:32048448:3
[5]
asset:table:pmid:32048448:4
steps array · 1 item
[0]
run_analysis
must_build object · 5 fields
dsl_operations array · 0 items
converters array · 0 items
readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
[0]
data:geo:GSE83456
gaps array · 0 items
review object · 5 fields
state
partial
machine_critique object · 5 fields
kind
extraction_review
reader object · 5 fields
model
MiniMax-M3.1-Flash
provider
minimax
provider_family
minimax
read_at
2026-10-31T18:18:12Z
independence
single_reader
evidence_check object · 2 fields
method
reordered
availability
verbatim
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3
usage object · 3 fields
prompt_tokens
34399
completion_tokens
990
cached_tokens
792
stages array · 1 item
[0] object · 4 fields
id
extraction
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complete
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MiniMax-M3.1-Flash
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minimax
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review.independent_reader
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review.machine_critique
[2]
review.human_critique
execution object · 5 fields
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absent
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not_run
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null
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gaps array · 1 item
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provenance object · 7 fields
entities array · 3 items
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id
pmid:32048448
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paper
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pmid:32048448
[1] object · 3 fields
id
source:pmid:32048448
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manuscript
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PMID 32048448 full text
[2] object · 3 fields
id
data:geo:GSE83456
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dataset
label
GEO GSE83456
activities array · 3 items
[0] object · 4 fields
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activity-reading-sci-2026-11-01
type
classification
used array · 3 items
[0] object · 3 fields
id
pmid:32048448
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paper
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pmid:32048448
[1] object · 3 fields
id
source:pmid:32048448
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manuscript
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PMID 32048448 full text
[2] object · 3 fields
id
data:geo:GSE83456
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dataset
label
GEO GSE83456
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agent:corpus-assay-engine
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source:pmid:32048448
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agent:minimax-reader
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id
activity-resolve-GSE83456
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accession_resolution
used array · 1 item
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data:geo:GSE83456
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agent:corpus-assay-engine
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agent:corpus-assay-engine
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agent:minimax-reader
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MiniMax literature reader
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343fb30756ba6ec3
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lineage object · 4 fields
parent_id
pmid:32048448
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sha256:b816cdf4c0e87e2ab866aa8456b4574035b2e4409a0a0b91c034b144361d83b0
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null
gaps array · 6 items
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execution.not_run
[3]
review.human_critique
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review.independent_reader
[5]
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assays array · 1 item
[0] object · 11 fields
role
analysis
definition_id
differential_expression
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f2132e96ae6c7a4e
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normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
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source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
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The original expression matrix was normalized and processed by R. The limma package was used to screen out differentially expressed genes. The P‐value of genes was calculated using t test method, and Benjamini and Hochberg's method was used to calculate the adjusted P‐value. The clinical samples of TB infection were retrieved from the GEO database. A total of 106 blood samples were selected from http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE83456, including 45 pulmonary tuberculosis (PTB) samples and 61 healthy control (HC) samples.
order_basis
analysis_only
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assay:1
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32048448", "kind": "science-record", "revision": 8, "content_hash": "sha256:689025db70ad61f4235affd84077ecb6c14877814a6377ee457ee97293b991b0", "created_at": "2026-11-01T15:40:56Z", "updated_at": "2026-11-01T22:44:34Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "STAT1 and its related molecules as potential biomarkers in Mycobacterium tuberculosis infection.", "doi": "10.1111/jcmm.14856", "pmid": "32048448", "authors": ["Xing-Hao Yi", "Bo Zhang", "Yu-Rong Fu", "Zheng-Jun Yi"], "journal": "Journal of cellular and molecular medicine", "year": 2020, "abstract": "Tuberculosis (TB) is a severe infectious disease that seriously endangers human health. The immune defence mechanism of the body against TB is still unclear. The purpose of this study was to find the key molecules involved in the immune defence response during TB infection, and provide reference for the treatment of TB and further understanding of the immune defence mechanism of the body. Data from GSE83456 were downloaded from GEO data sets for analysis, and a total of 192 differentially expressed genes were screened out. Most of these genes are enriched in the interferon signalling pathway and are defence response-related. We also found that STAT1 plays an important role in the immune defence of TB infection and it is one of the key genes related to interferon signalling pathway. STAT1-related molecules including hsa-miR-448, hsa-miR-223-3p, SAMD8_hsa_circRNA 994 and TWF1_hsa_circRNA 9897 were therefore screened out. Furthermore, expression levels of hsa-miR-448 and hsa-miR-223-3p were then verified by qRT-PCR. Results showed that both hsa-miR-448 and hsa-miR-223-3p were down-regulated in plasma from patients with pulmonary TB. Taken together, our data indicate that an mRNA-miRNA-circRNA interaction chain may play an important role in the infection of MTB, and STAT1 and related molecules including hsa-miR-223-3p, has-miR-448, SAMD8_hsa_circRNA994 and TWF1_hsa_circRNA9897 were identified as potential biomarkers in the development of active TB.", "claims": [{"id": "claim-method", "statement": "The original expression matrix was normalized and processed by R. The limma package was used to screen out differentially expressed genes. The P‐value of genes was calculated using t test method, and Benjamini and Hochberg's method was used to calculate the adjusted P‐value. The clinical samples of TB infection were retrieved from the GEO database. 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This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE83456"], "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:GSE83456"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32048448", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1111/jcmm.14856", "sha256": 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Specific data of gene clusters were exported and presented in a tabular form", "structure": {"pmcid": "PMC7077527", "section_index": 13, "section_title": "Construction of protein‐protein interaction (PPI) network and further excavation of gene clusters involved in immune system–related biological pathway", "row_count": 8, "column_count": 5}, "table": {"label": "Table 2", "caption": "MCODE was used to process the data downloaded from the STRING to further mining gene clusters. Specific data of gene clusters were exported and presented in a tabular form", "rows": [["Cluster", "Score (Density*#Nodes)", "Nodes", "Edges", "Node IDs"], ["1", "34.973", "38", "647", "RTP4, UBE2L6, IFI44L, PLSCRl, DDX60, IFI6, SAMD9L, OAS2, IFI44, XAFI, IFITM3, PARP9, EPSTil, IFITMl, IRF7, HERC5, GBP2, GBPl, IFIT2, TRIM22, STAT2, OASl, IFI27, RSAD2, IFIT5, IFI35, CMPK2, ISG15, DDX58, STATl, LY6E, IFIHl, IFITl,IFIT3, CXCLlO, OASL, MXl, OAS3"], ["2", "4", "4", "6", "FCGRlA, FCGRlB, MT2A, GBP6"], ["3", "4", "4", "6", "PLAUR, CLEC4D, GPR84, CEACAMl"], ["4", "4", "4", "6", "SERPINGl, C2, CIQB, CIQC"], ["5", "3.333", "4", "5", "CCR7, CCRL2, CD27, CD38"], ["6", "3", "3", "3", "SlPRl, GPR183, P2RY14"], ["7", "3", "3", "3", "CASP5, CARD16, CARD17"]], "row_count": 8, "column_count": 5, "numeric_cells": 33, "header_rows": 1, "locator": "section[13]/table-wrap[1]#jcmm14856-tbl-0002"}}, {"id": "asset:table:pmid:32048448:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7bb4b7dd4148b262230f2503d38c775a7d282ff9399250afe1536573083c7c26", "bytes": 783, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[2]#jcmm14856-tbl-0003", "version": null, "note": "Top 10 biological processes enriched in cluster 1", "structure": {"pmcid": "PMC7077527", "section_index": 13, "section_title": "Construction of protein‐protein interaction (PPI) network and further excavation of gene clusters involved in immune system–related biological pathway", "row_count": 11, "column_count": 3}, "table": {"label": "Table 3", "caption": "Top 10 biological processes enriched in cluster 1", "rows": [["Biological process", "Gene count", "False discovery rate"], ["Defence response to virus", "29", "8.03 × 10−45"], ["Response to virus", "30", "1.44 × 10−42"], ["Type I interferon signalling pathway", "21", "8.30 × 10−37"], ["Innate immune response", "31", "1.67 × 10−33"], ["Response to other organism", "32", "1.40 × 10−32"], ["Defence response", "35", "1.6 × 10−32"], ["Immune response", "32", "2.0 × 10−24"], ["Cytokine‐mediated signalling pathway", "25", "5.8 × 10−24"], ["Immune system process", "35", "4.2 × 10−23"], ["Response to stress", "37", "3.00 × 10−21"]], "row_count": 11, "column_count": 3, "numeric_cells": 20, "header_rows": 1, "locator": "section[13]/table-wrap[2]#jcmm14856-tbl-0003"}}, {"id": "asset:table:pmid:32048448:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:19d9c6f07c233e7fdc1819e6b45c3ec98b9465bef01e22cacf461076a326107e", "bytes": 556, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#jcmm14856-tbl-0004", "version": null, "note": "miRNAs and its target genes", "structure": {"pmcid": "PMC7077527", "section_index": 14, "section_title": "Further miRNA mining and interaction network analysis", "row_count": 10, "column_count": 3}, "table": {"label": "Table 4", "caption": "miRNAs and its target genes", "rows": [["miRNA", "Genes targeted By miRNA", "Gene count"], ["miR‐130a‐5p", "GBP1, IFIT2", "2"], ["miR‐605‐5p", "GBP1, 0AS3", "2"], ["miR‐223‐3p", "MX1, STAT1", "2"], ["miR‐1231", "OAS3, STAT1", "2"], ["miR‐3915", "IFIT2, MX1", "2"], ["miR‐3918", "OAS2, DDX58", "2"], ["miR‐448", "STAT1, 0AS2", "2"], ["miR‐936", "DDX58, IFIT2", "2"], ["miR‐181a‐2‐3p", "STATl, OAS3", "2"]], "row_count": 10, "column_count": 3, "numeric_cells": 22, "header_rows": 1, "locator": "section[14]/table-wrap[1]#jcmm14856-tbl-0004"}}], "gaps": ["asset:data:geo:GSE83456 not downloaded", "asset:data:geo:GSE83456 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "reordered", "quote": "The original expression matrix was normalized and processed by R. The limma package was used to screen out differentially expressed genes. The P‐value of genes was calculated using t test method, and Benjamini and Hochberg's method was used to calculate the adjusted P‐value. The clinical samples of TB infection were retrieved from the GEO database. A total of 106 blood samples were selected from http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE83456, including 45 pulmonary tuberculosis (PTB) samples and 61 healthy control (HC) samples."}}, {"id": "method-2", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "pathway enrichment"}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "capability": {"tier": "R1", "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": {"tier": "R1", "reachable": true, "accessions": ["GSE83456"], "resolved_accessions": ["GSE83456"], "statements": ["Data sets used and analysed during the current study are available from the corresponding author on reasonable request."], "basis": "The paper names GSE83456 in NCBI Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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