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pmid:35333898

Update of gene expression/methylation and MiRNA profiling in colorectal cancer; application in diagnosis, prognosis, and targeted therapy.

Amir Mehrgou · Shahram Teimourian

PloS one · 2022 doi:10.1371/journal.pone.0265527

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

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title
Update of gene expression/methylation and MiRNA profiling in colorectal cancer; application in diagnosis, prognosis, and targeted therapy.
doi
10.1371/journal.pone.0265527
pmid
35333898
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[0]
Amir Mehrgou
[1]
Shahram Teimourian
journal
PloS one
year
2022
abstract
BACKGROUND: Colorectal cancer is one of the most deadliest malignancies worldwide. Due to the dearth of appropriate biomarkers, the diagnosis of this mortal disease is usually deferred, in its turn, culminating in the failure of prevention. By the same token, proper biomarkers are at play in determining the quality of prognosis. In other words, the survival rate is contingent upon the regulation of such biomarkers. MATERIALS AND METHODS: The information regarding expression (GSE41258, and GSE31905), methylation (GSE101764), and miRNA (dbDEMC) were downloaded. MEXPRESS and GEPIA confirmed the validated differentially expressed/methylated genes using TCGA data. Taking advantage of the correlation plots and receiver-operating-characteristic (ROC) curves, expression and methylation profiles were compared. The interactions between validated differentially expressed genes and differentially expressed miRNA were recognized and visualized by miRTarBase and Cytoscape, respectively. Then, the protein-protein interaction (PPI) network and hub genes were established via STRING and Cytohubba plugin. Utilizing R packages (DOSE, Enrichplot, and clusterProfiler) and DAVID database, the Functional Enrichment analysis and the detection of KEGG pathways were performed. Ultimately, in order to recognize the prognostic value of found biomarkers, they were evaluated through drawing survival plots for CRC patients. RESULTS: In this research, we found an expression profile (with 13 novel genes), a methylation profile (with two novel genes), and a miRNA profile with diagnostic value. Concerning diagnosis, the expression profile was evaluated more powerful in comparison with the methylation profile. Furthermore, a prognosis-related expression profile was detected. CONCLUSION: In addition to diagnostic- and prognostic-applicability, the discerned profiles can assist in targeted therapy and current therapeutic strategies.
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Utilizing GEO2R, an online differentially analyzing tool, and “GEOquery” (Version 2.54.0) [66], and “Limma” (Version 3.42.0) [67] R (Version 3.6.3) packages, we exerted log2 transformation and Benjamini & Hochberg method on GSE41258 to find the differentially expressed genes in a case/control comparison manner.
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sections[17] "5.2. Identification of Differentially Expressed Genes (DEGs) and Differentially Methylated Genes (DMGs)" paragraph 2
quote
Utilizing GEO2R, an online differentially analyzing tool, and “GEOquery” (Version 2.54.0) [66], and “Limma” (Version 3.42.0) [67] R (Version 3.6.3) packages, we exerted log2 transformation and Benjamini & Hochberg method on GSE41258 to find the differentially expressed genes in a case/control comparison manner.
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The datasets supporting the conclusions of this article are available in the Gene Expression Omnibus repository, [https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE41258 (GSE41258), https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE101764 (GSE101764), https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31905 (GSE31905)].
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sections[30] "Data Availability" paragraph 2
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The datasets supporting the conclusions of this article are available in the Gene Expression Omnibus repository, [https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE41258 (GSE41258), https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE101764 (GSE101764), https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31905 (GSE31905)].
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In this research, we found an expression profile (with 13 novel genes), a methylation profile (with two novel genes), and a miRNA profile with diagnostic value.
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In this research, we found an expression profile (with 13 novel genes), a methylation profile (with two novel genes), and a miRNA profile with diagnostic value.
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In this research, we found an expression profile (with 13 novel genes), a methylation profile (with two novel genes), and a miRNA profile with diagnostic value.
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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]
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[43]
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[44]
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[67]
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[118]
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[130]
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[132]
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[135]
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[150]
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[151]
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[160]
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[161]
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[162]
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[163]
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[195]
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[196]
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[200]
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[201]
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[202]
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[211]
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[214]
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[216]
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[218]
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[219]
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[220]
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[221]
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[222]
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[223]
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[224]
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[225]
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[226]
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[227]
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[228]
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[229]
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[230]
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[232]
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[235]
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[240]
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[255]
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[256]
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[263]
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[304]
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sample_count
390
group_sizes
null
group_sizes_basis
null
platform
96
taxon
Homo sapiens
title
Expression data from colorectal cancer patients
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 6 items
[0]
asset:data:geo:GSE101764 not downloaded
[1]
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[2]
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[3]
asset:data:geo:GSE31905 licence not read
[4]
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[5]
asset:data:geo:GSE41258 licence not read
analysis object · 4 fields
state
partial
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[0] object · 10 fields
id
method-1
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survival_analysis
specific
kaplan_meier
label
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[0]
survival_km
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parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.8
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high
quote
Kaplan-Meier
[1] object · 10 fields
id
method-2
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differential_expression
specific
limma_voom
label
Differential expression analysis
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[0]
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[1]
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[2]
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missing_operations array · 0 items
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[0]
count_matrix_with_condition
evidence object · 3 fields
score
0.8
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high
quote
Limma
[2] object · 10 fields
id
method-3
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network_analysis
specific
ppi_network
label
Network / pathway analysis
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[0]
build_graph
[1]
centrality_scores
[2]
pathway_enrich
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[0]
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evidence object · 3 fields
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0.7
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quote
protein-protein interaction
[3] object · 10 fields
id
method-4
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null
specific
null
label
Benjamini & Hochberg method
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missing_operations array · 0 items
parameters object · 0 fields
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evidence object · 3 fields
score
1
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verbatim
quote
Utilizing GEO2R, an online differentially analyzing tool, and “GEOquery” (Version 2.54.0) [66], and “Limma” (Version 3.42.0) [67] R (Version 3.6.3) packages, we exerted log2 transformation and Benjamini & Hochberg method on GSE41258 to find the differentially expressed genes in a case/control comparison manner.
targets array · 0 items
gaps array · 1 item
[0]
method.reader_named_unmapped
capability object · 3 fields
state
complete
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[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
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[0]
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[1]
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[3]
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[4]
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[5]
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[6]
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[7]
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[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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[0]
survival_km
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basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier.
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 · 3 items
[0]
GSE41258
[1]
GSE101764
[2]
GSE31905
resolved_accessions array · 3 items
[0]
GSE41258
[1]
GSE101764
[2]
GSE31905
statements array · 1 item
[0]
The datasets supporting the conclusions of this article are available in the Gene Expression Omnibus repository, [https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE41258 (GSE41258), https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE101764 (GSE101764), https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31905 (GSE31905)].
basis
The paper names GSE41258, GSE101764, GSE31905 in Gene Expression Omnibus repository and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 1 item
[0]
survival_km
assets array · 2 items
[0]
source:pmid:35333898
[1]
data:geo:GSE101764
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[0]
run_analysis
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readers array · 0 items
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data_gaps array · 1 item
[0]
data:geo:GSE101764
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
2026-11-01T17:39:11Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
19694
completion_tokens
2019
cached_tokens
128
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[0] object · 4 fields
id
extraction
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complete
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MiniMax-M3.1-Flash
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[2]
review.human_critique
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[0]
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[0] object · 3 fields
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pmid:35333898
type
paper
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pmid:35333898
[1] object · 3 fields
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source:pmid:35333898
type
manuscript
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PMID 35333898 full text
[2] object · 3 fields
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data:geo:GSE101764
type
dataset
label
GEO GSE101764
activities array · 3 items
[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
used array · 3 items
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paper
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pmid:35333898
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source:pmid:35333898
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PMID 35333898 full text
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data:geo:GSE101764
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dataset
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GEO GSE101764
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agent:corpus-assay-engine
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extraction
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agent:minimax-reader
[2] object · 4 fields
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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f2132e96ae6c7a4e
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supported
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f2132e96ae6c7a4e
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35333898", "kind": "science-record", "revision": 4, "content_hash": "sha256:52f28689a11725eaab21ecf90a298f7fcce0178d41bd75854e92aab2e788252d", "created_at": "2026-11-01T18:14:08Z", "updated_at": "2026-11-01T22:06:10Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Update of gene expression/methylation and MiRNA profiling in colorectal cancer; application in diagnosis, prognosis, and targeted therapy.", "doi": "10.1371/journal.pone.0265527", "pmid": "35333898", "authors": ["Amir Mehrgou", "Shahram Teimourian"], "journal": "PloS one", "year": 2022, "abstract": "BACKGROUND: Colorectal cancer is one of the most deadliest malignancies worldwide. Due to the dearth of appropriate biomarkers, the diagnosis of this mortal disease is usually deferred, in its turn, culminating in the failure of prevention. By the same token, proper biomarkers are at play in determining the quality of prognosis. In other words, the survival rate is contingent upon the regulation of such biomarkers.\nMATERIALS AND METHODS: The information regarding expression (GSE41258, and GSE31905), methylation (GSE101764), and miRNA (dbDEMC) were downloaded. MEXPRESS and GEPIA confirmed the validated differentially expressed/methylated genes using TCGA data. Taking advantage of the correlation plots and receiver-operating-characteristic (ROC) curves, expression and methylation profiles were compared. The interactions between validated differentially expressed genes and differentially expressed miRNA were recognized and visualized by miRTarBase and Cytoscape, respectively. Then, the protein-protein interaction (PPI) network and hub genes were established via STRING and Cytohubba plugin. Utilizing R packages (DOSE, Enrichplot, and clusterProfiler) and DAVID database, the Functional Enrichment analysis and the detection of KEGG pathways were performed. Ultimately, in order to recognize the prognostic value of found biomarkers, they were evaluated through drawing survival plots for CRC patients.\nRESULTS: In this research, we found an expression profile (with 13 novel genes), a methylation profile (with two novel genes), and a miRNA profile with diagnostic value. Concerning diagnosis, the expression profile was evaluated more powerful in comparison with the methylation profile. Furthermore, a prognosis-related expression profile was detected.\nCONCLUSION: In addition to diagnostic- and prognostic-applicability, the discerned profiles can assist in targeted therapy and current therapeutic strategies.", "claims": [{"id": "claim-method", "statement": "Utilizing GEO2R, an online differentially analyzing tool, and “GEOquery” (Version 2.54.0) [66], and “Limma” (Version 3.42.0) [67] R (Version 3.6.3) packages, we exerted log2 transformation and Benjamini & Hochberg method on GSE41258 to find the differentially expressed genes in a case/control comparison manner.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35333898", "locator": "sections[17] \"5.2. Identification of Differentially Expressed Genes (DEGs) and Differentially Methylated Genes (DMGs)\" paragraph 2", "quote": "Utilizing GEO2R, an online differentially analyzing tool, and “GEOquery” (Version 2.54.0) [66], and “Limma” (Version 3.42.0) [67] R (Version 3.6.3) packages, we exerted log2 transformation and Benjamini & Hochberg method on GSE41258 to find the differentially expressed genes in a case/control comparison manner."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets supporting the conclusions of this article are available in the Gene Expression Omnibus repository, [https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE41258 (GSE41258), https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE101764 (GSE101764), https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31905 (GSE31905)].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35333898", "locator": "sections[30] \"Data Availability\" paragraph 2", "quote": "The datasets supporting the conclusions of this article are available in the Gene Expression Omnibus repository, [https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE41258 (GSE41258), https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE101764 (GSE101764), https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31905 (GSE31905)]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In this research, we found an expression profile (with 13 novel genes), a methylation profile (with two novel genes), and a miRNA profile with diagnostic value.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35333898", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "In this research, we found an expression profile (with 13 novel genes), a methylation profile (with two novel genes), and a miRNA profile with diagnostic value."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "In this research, we found an expression profile (with 13 novel genes), a methylation profile (with two novel genes), and a miRNA profile with diagnostic value.", "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:35333898"], "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:GSE101764"], "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:GSE101764"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35333898", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1371/journal.pone.0265527", "sha256": 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"GSM1012666", "GSM1012667"], "sample_count": 390, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Expression data from colorectal cancer patients", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE101764 not downloaded", "asset:data:geo:GSE101764 licence not read", "asset:data:geo:GSE31905 not downloaded", "asset:data:geo:GSE31905 licence not read", "asset:data:geo:GSE41258 not downloaded", "asset:data:geo:GSE41258 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": 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"band": "verbatim", "quote": "Utilizing GEO2R, an online differentially analyzing tool, and “GEOquery” (Version 2.54.0) [66], and “Limma” (Version 3.42.0) [67] R (Version 3.6.3) packages, we exerted log2 transformation and Benjamini & Hochberg method on GSE41258 to find the differentially expressed genes in a case/control comparison manner."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": ["survival_km"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier."}, "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": ["GSE41258", "GSE101764", "GSE31905"], "resolved_accessions": ["GSE41258", "GSE101764", "GSE31905"], "statements": ["The datasets supporting the conclusions of this article are available in the Gene Expression Omnibus repository, [https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE41258 (GSE41258), https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE101764 (GSE101764), https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31905 (GSE31905)]."], "basis": "The paper names GSE41258, GSE101764, GSE31905 in Gene Expression Omnibus repository and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["survival_km"], "assets": ["source:pmid:35333898", "data:geo:GSE101764"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE101764"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:39:11Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 19694, "completion_tokens": 2019, "cached_tokens": 128}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:35333898", "type": "paper", "label": "pmid:35333898"}, {"id": "source:pmid:35333898", "type": "manuscript", "label": "PMID 35333898 full text"}, {"id": "data:geo:GSE101764", "type": "dataset", "label": "GEO GSE101764"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35333898", "type": "paper", "label": "pmid:35333898"}, {"id": "source:pmid:35333898", "type": "manuscript", "label": "PMID 35333898 full text"}, {"id": "data:geo:GSE101764", "type": "dataset", "label": "GEO GSE101764"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35333898", "type": "extraction", "used": ["source:pmid:35333898"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE101764", "type": "accession_resolution", "used": ["data:geo:GSE101764"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:35333898", "parent_hash": "sha256:763766db01099420bceb7f8a2d2f5bfca5ed3ab9f79ba1d4aa3a3a69dff6b5f7", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE101764 licence not read", "asset:data:geo:GSE101764 not downloaded", "asset:data:geo:GSE31905 licence not read", "asset:data:geo:GSE31905 not downloaded", "asset:data:geo:GSE41258 licence not read", "asset:data:geo:GSE41258 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Kaplan-Meier"], "order_basis": "analysis_only", "id": "assay:1"}]}