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pmid:39108890

Analysis of machine learning based integration to identify the crosslink between inflammation and immune response in non-alcoholic fatty liver disease through bioinformatic analysis.

Runzhi Yu · Yiqin Huang · Xiaona Hu · Jie Chen

Heliyon · 2024 doi:10.1016/j.heliyon.2024.e32783

Paper

complete

Experiment

complete

Data

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title
Analysis of machine learning based integration to identify the crosslink between inflammation and immune response in non-alcoholic fatty liver disease through bioinformatic analysis.
doi
10.1016/j.heliyon.2024.e32783
pmid
39108890
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[0]
Runzhi Yu
[1]
Yiqin Huang
[2]
Xiaona Hu
[3]
Jie Chen
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Heliyon
year
2024
abstract
Background: The prevalence of nonalcoholic fatty liver disease (NAFLD) is a major form of chronic liver disease. This study aimed to scrutinize the diagnostic biomarkers of NAFLD and their correlation with the immune microenvironment through bioinformatic analysis. Methods: To identify genes associated with nonalcoholic fatty liver disease (NAFLD), we obtained microarray datasets (GSE63067 and GSE89632) from the Gene Expression Omnibus (GEO) database. Machine learning techniques such as Support Vector Machine (SVM), Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest (RF) were used to identify key genes. We performed gene ontology analysis to identify the driver pathways of NAFLD. External datasets (merging GSE48452, GSE66676 and GSE135251) were used to validate the identified genes and confirm protein levels by Western blotting. The CIBERSORT algorithm and immune-related techniques, such as ssGSEA, were used to assess the level of infiltration of different immune cell types and their functions. Finally, Spearman's analysis confirmed the relationship between pivotal genes and immune cells. Results: Hub genes (BBOX1, FOSB, NR4A2, RAB26 and SOCS2) were identified as potential biomarkers. This study demonstrates that these hub genes are significantly dysregulated in NAFLD, suggesting that they may be useful as diagnostic indicators and possible targets for treatment. Also covered are their possible effects on inflammation, immune cell activation, and liver damage in NAFLD. A better understanding of the intricate relationship between metabolic inefficiency, immunological response, and liver pathology in NAFLD may be gained from this work, which can lead to the development of new diagnostic tools and clinical treatments. Conclusion: The current study identified BBOX1, FOSB, NR4A2, RAB26 and SOCS2 as important diagnostic biomarkers for NAFLD. The study highlights the important function of immune cell infiltration in developing NAFLD. Their findings provide valuable molecular biological insights into the development of NAFLD and may lead to novel therapeutic strategies for treating this disease.
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To determine the differential expression (DEGs) between NAFLD samples and control samples, we performed differential expression analysis using the R package “limma” with set criteria of | logFC| > 0.5 and p-value <0.05.
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To determine the differential expression (DEGs) between NAFLD samples and control samples, we performed differential expression analysis using the R package “limma” with set criteria of | logFC| > 0.5 and p-value <0.05.
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This study utilized publicly available datasets, which can be accessed at the following link: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE63067 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE89632 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE135251 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE48452 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66676.
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This study utilized publicly available datasets, which can be accessed at the following link: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE63067 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE89632 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE135251 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE48452 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66676.
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Subsequently, 596 DEGs were identified, including 346 down-regulated genes and 250 up-regulated genes.
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Subsequently, 596 DEGs were identified (Supplementary Table 2), including 346 down-regulated genes and 250 up-regulated genes, shown in the heat map (Fig. 1B).
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TRANSCRIPTOMIC PROFILING ACROSS THE SPECTRUM OF NON-ALCOHOLIC FATTY LIVER DISEASE
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https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66676
sha256
null
bytes
null
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resolved
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null
reader_status
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identifier
GSE66676
version
null
note
This study utilized publicly available datasets, which can be accessed at the following link: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE63067 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE89632 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE135251 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE48452 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66676.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
This study utilized publicly available datasets, which can be accessed at the following link: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE63067 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE89632 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE135251 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE48452 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66676.
access_statement_kind
data_availability_statement
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GSM1627740
[1]
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[21]
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[23]
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[26]
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[28]
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[29]
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[31]
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[32]
GSM1627772
[33]
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[34]
GSM1627774
[35]
GSM1627775
[36]
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[37]
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[38]
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[39]
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[40]
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[41]
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[42]
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[43]
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[44]
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[45]
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[46]
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[47]
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[48]
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[49]
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[50]
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[51]
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[52]
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[53]
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[54]
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[55]
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[56]
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[57]
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[58]
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[59]
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[60]
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[61]
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[62]
GSM1627802
[63]
GSM1627803
[64]
GSM1627804
[65]
GSM1627805
[66]
GSM1627806
sample_count
67
group_sizes
null
group_sizes_basis
null
platform
6244
taxon
Homo sapiens
title
Nonalcoholic steatohepatitis in adolescents undergoing bariatric surgery
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[5] object · 15 fields
id
data:geo:GSE89632
role
raw
format
geo-series
media_type
application/vnd.ncbi.geo-series+json
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https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE89632
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null
bytes
null
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resolved
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null
reader_status
reader_required
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GSE89632
version
null
note
This study utilized publicly available datasets, which can be accessed at the following link: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE63067 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE89632 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE135251 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE48452 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66676.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
This study utilized publicly available datasets, which can be accessed at the following link: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE63067 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE89632 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE135251 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE48452 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66676.
access_statement_kind
data_availability_statement
sample_accessions array · 63 items
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[13]
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[20]
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[21]
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[22]
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[23]
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[24]
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[25]
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[26]
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[27]
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[28]
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[29]
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[30]
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[31]
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[32]
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[33]
GSM2385753
[34]
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[35]
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[36]
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[37]
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[38]
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[39]
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[40]
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[41]
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[42]
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[43]
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[44]
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[45]
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[46]
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[47]
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[48]
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[49]
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[50]
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[51]
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[52]
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[53]
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[54]
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[55]
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[56]
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[57]
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[58]
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[59]
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[60]
GSM2385780
[61]
GSM2385781
[62]
GSM2385782
sample_count
63
group_sizes
null
group_sizes_basis
null
platform
14951
taxon
Homo sapiens
title
Genome-wide analysis of hepatic gene expression in patients with non-alcoholic fatty liver disease and in healthy donors in relation to hepatic fatty acid composition and other nutritional factors
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 10 items
[0]
asset:data:geo:GSE135251 not downloaded
[1]
asset:data:geo:GSE135251 licence not read
[2]
asset:data:geo:GSE48452 not downloaded
[3]
asset:data:geo:GSE48452 licence not read
[4]
asset:data:geo:GSE63067 not downloaded
[5]
asset:data:geo:GSE63067 licence not read
[6]
asset:data:geo:GSE66676 not downloaded
[7]
asset:data:geo:GSE66676 licence not read
[8]
asset:data:geo:GSE89632 not downloaded
[9]
asset:data:geo:GSE89632 licence not read
analysis object · 4 fields
state
partial
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[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
parameters object · 0 fields
data_shapes array · 1 item
[0]
count_matrix_with_condition
evidence object · 3 fields
score
1
band
verbatim
quote
To determine the differential expression (DEGs) between NAFLD samples and control samples, we performed differential expression analysis using the R package “limma” with set criteria of | logFC| > 0.5 and p-value <0.05.
[1] object · 10 fields
id
method-2
family
group_comparison
specific
student_t_test
label
Group comparison
dsl_operations array · 0 items
missing_operations array · 1 item
[0]
student_t
expressible
false
parameters object · 0 fields
data_shapes array · 1 item
[0]
two_or_more_groups_continuous
evidence object · 3 fields
score
0.8
band
high
quote
Student's t-test
[2] object · 10 fields
id
method-3
family
group_comparison
specific
wilcoxon
label
Group comparison
dsl_operations array · 0 items
missing_operations array · 1 item
[0]
group_comparison_wilcoxon
expressible
false
parameters object · 0 fields
data_shapes array · 1 item
[0]
two_or_more_groups_continuous
evidence object · 3 fields
score
0.8
band
high
quote
Wilcoxon
[3] object · 10 fields
id
method-4
family
machine_learning
specific
random_forest
label
Machine learning
dsl_operations array · 0 items
missing_operations array · 1 item
[0]
machine_learning_random_forest
expressible
false
parameters object · 0 fields
data_shapes array · 1 item
[0]
labelled_feature_matrix
evidence object · 3 fields
score
0.7
band
medium
quote
Random Forest
[4] object · 10 fields
id
method-5
family
machine_learning
specific
support_vector_machine
label
Machine learning
dsl_operations array · 3 items
[0]
train_classifier
[1]
cross_validate
[2]
roc_auc
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
labelled_feature_matrix
evidence object · 3 fields
score
0.7
band
medium
quote
Support Vector Machine
[5] object · 10 fields
id
method-6
family
correlation_analysis
specific
pearson
label
Correlation analysis
dsl_operations array · 1 item
[0]
pearson_r
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
paired_numeric_columns
evidence object · 3 fields
score
0.8
band
high
quote
Pearson correlation
[6] object · 10 fields
id
method-7
family
correlation_analysis
specific
spearman
label
Correlation analysis
dsl_operations array · 1 item
[0]
spearman_rho
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
paired_numeric_columns
evidence object · 3 fields
score
0.8
band
high
quote
Spearman correlation
[7] object · 10 fields
id
method-8
family
network_analysis
specific
ppi_network
label
Network / pathway analysis
dsl_operations array · 3 items
[0]
build_graph
[1]
centrality_scores
[2]
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
band
high
quote
Protein-Protein Interaction
targets array · 0 items
gaps array · 1 item
[0]
method.reader_differs_from_extractor
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
expressible
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 · 5 items
[0]
GSE63067
[1]
GSE89632
[2]
GSE48452
[3]
GSE66676
[4]
GSE135251
resolved_accessions array · 5 items
[0]
GSE63067
[1]
GSE89632
[2]
GSE48452
[3]
GSE66676
[4]
GSE135251
statements array · 1 item
[0]
This study utilized publicly available datasets, which can be accessed at the following link: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE63067 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE89632 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE135251 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE48452 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66676.
basis
The paper names GSE63067, GSE89632, GSE48452, GSE66676, GSE135251 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
dsl_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
assets array · 2 items
[0]
source:pmid:39108890
[1]
data:geo:GSE135251
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:GSE135251
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
2026-11-01T19:26:47Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
13146
completion_tokens
1526
cached_tokens
256
stages array · 1 item
[0] object · 4 fields
id
extraction
state
complete
reader
MiniMax-M3.1-Flash
provider
minimax
gaps array · 3 items
[0]
review.independent_reader
[1]
review.machine_critique
[2]
review.human_critique
execution object · 5 fields
state
absent
status
not_run
mode
null
runs array · 0 items
gaps array · 1 item
[0]
execution.not_run
provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:39108890
type
paper
label
pmid:39108890
[1] object · 3 fields
id
source:pmid:39108890
type
manuscript
label
PMID 39108890 full text
[2] object · 3 fields
id
data:geo:GSE135251
type
dataset
label
GEO GSE135251
activities array · 3 items
[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
used array · 3 items
[0] object · 3 fields
id
pmid:39108890
type
paper
label
pmid:39108890
[1] object · 3 fields
id
source:pmid:39108890
type
manuscript
label
PMID 39108890 full text
[2] object · 3 fields
id
data:geo:GSE135251
type
dataset
label
GEO GSE135251
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-39108890
type
extraction
used array · 1 item
[0]
source:pmid:39108890
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE135251
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE135251
agent
agent:corpus-assay-engine
agents array · 2 items
[0] object · 3 fields
id
agent:corpus-assay-engine
type
software
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Corpus assay engine
[1] object · 3 fields
id
agent:minimax-reader
type
software
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MiniMax literature reader
source_run_id
reading-sci-2026-11-01
dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
2cb3e42f047d2ecf
snapshot_id
ba34b49490d9bfaf
lineage object · 4 fields
parent_id
pmid:39108890
parent_hash
sha256:6a26397e6019878dab0721a1fa3d6d814f0c499384adea5ade1e7fbf684ba704
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null
gaps array · 15 items
[0]
asset:data:geo:GSE135251 licence not read
[1]
asset:data:geo:GSE135251 not downloaded
[2]
asset:data:geo:GSE48452 licence not read
[3]
asset:data:geo:GSE48452 not downloaded
[4]
asset:data:geo:GSE63067 licence not read
[5]
asset:data:geo:GSE63067 not downloaded
[6]
asset:data:geo:GSE66676 licence not read
[7]
asset:data:geo:GSE66676 not downloaded
[8]
asset:data:geo:GSE89632 licence not read
[9]
asset:data:geo:GSE89632 not downloaded
[10]
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[11]
method.reader_differs_from_extractor
[12]
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[13]
review.independent_reader
[14]
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[0] object · 11 fields
role
data_generation
definition_id
microarray
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.93
evidence array · 1 item
[0]
lic fatty liver disease (NAFLD), we obtained microarray datasets (GSE63067 and GSE89632) from the Ge
order_basis
paper_text_order:501
id
assay:1
[1] object · 11 fields
role
data_generation
definition_id
western_blot
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.93
evidence array · 1 item
[0]
entified genes and confirm protein levels by Western blotting. The CIBERSORT algorithm and immune-related
order_basis
paper_text_order:984
id
assay:2
[2] object · 11 fields
role
analysis
definition_id
differential_expression
definition_version
f2132e96ae6c7a4e
required_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
To determine the differential expression (DEGs) between NAFLD samples and control samples, we performed differential expression analysis using the R package “limma” with set criteria of | logFC| > 0.5 and p-value <0.05.
order_basis
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:39108890", "kind": "science-record", "revision": 4, "content_hash": "sha256:a7b5c1ad1c36b0b48f6042e3a04d15e94499db8962020387441f7d003990e992", "created_at": "2026-11-01T20:29:12Z", "updated_at": "2026-11-01T22:54:52Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Analysis of machine learning based integration to identify the crosslink between inflammation and immune response in non-alcoholic fatty liver disease through bioinformatic analysis.", "doi": "10.1016/j.heliyon.2024.e32783", "pmid": "39108890", "authors": ["Runzhi Yu", "Yiqin Huang", "Xiaona Hu", "Jie Chen"], "journal": "Heliyon", "year": 2024, "abstract": "Background: The prevalence of nonalcoholic fatty liver disease (NAFLD) is a major form of chronic liver disease. This study aimed to scrutinize the diagnostic biomarkers of NAFLD and their correlation with the immune microenvironment through bioinformatic analysis.\nMethods: To identify genes associated with nonalcoholic fatty liver disease (NAFLD), we obtained microarray datasets (GSE63067 and GSE89632) from the Gene Expression Omnibus (GEO) database. Machine learning techniques such as Support Vector Machine (SVM), Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest (RF) were used to identify key genes. We performed gene ontology analysis to identify the driver pathways of NAFLD. External datasets (merging GSE48452, GSE66676 and GSE135251) were used to validate the identified genes and confirm protein levels by Western blotting. The CIBERSORT algorithm and immune-related techniques, such as ssGSEA, were used to assess the level of infiltration of different immune cell types and their functions. Finally, Spearman's analysis confirmed the relationship between pivotal genes and immune cells.\nResults: Hub genes (BBOX1, FOSB, NR4A2, RAB26 and SOCS2) were identified as potential biomarkers. This study demonstrates that these hub genes are significantly dysregulated in NAFLD, suggesting that they may be useful as diagnostic indicators and possible targets for treatment. Also covered are their possible effects on inflammation, immune cell activation, and liver damage in NAFLD. A better understanding of the intricate relationship between metabolic inefficiency, immunological response, and liver pathology in NAFLD may be gained from this work, which can lead to the development of new diagnostic tools and clinical treatments.\nConclusion: The current study identified BBOX1, FOSB, NR4A2, RAB26 and SOCS2 as important diagnostic biomarkers for NAFLD. The study highlights the important function of immune cell infiltration in developing NAFLD. 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"platform": "18573", "taxon": "Homo sapiens", "title": "TRANSCRIPTOMIC PROFILING ACROSS THE SPECTRUM OF NON-ALCOHOLIC FATTY LIVER DISEASE", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE48452", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE48452", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE48452", "version": null, "note": "This study utilized publicly available datasets, which can be accessed at the following link: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE63067 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE89632 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE135251 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