Corpus Engine Towards a reproducible .science file.
← All .science files

pmid:35721104

CLP1 is a Prognosis-Related Biomarker and Correlates With Immune Infiltrates in Rheumatoid Arthritis.

Zhenyu Zhao · Shaojie He · Sheng Tang · Xiaofeng Lai · Jie Ren · XinCheng Yu · Jinhua Lin · Mohan Wang · Mariya M El Akkawi · Shan Zeng · Dingsheng Zha

Frontiers in pharmacology · 2022 doi:10.3389/fphar.2022.827215

Paper

complete

Experiment

partial

Data

partial

Analysis

partial

Execution

absent

Execution evidence has not yet been added to this .science file. Explore its methods, data and open questions to plan the next step.
Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
id
pmid:35721104
kind
science-record
content_hash
sha256:2e15f9b6d6336ad65a7165961ffd82448db18bf2045debf9ad061afc652311ef
schema
https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json
created_at
2026-11-01T18:14:43Z
updated_at
2026-11-01T22:49:21Z
generator object · 2 fields
name
corpus-assay-engine
run_id
reading-sci-2026-11-01
paper object · 10 fields
state
complete
title
CLP1 is a Prognosis-Related Biomarker and Correlates With Immune Infiltrates in Rheumatoid Arthritis.
doi
10.3389/fphar.2022.827215
pmid
35721104
authors array · 11 items
[0]
Zhenyu Zhao
[1]
Shaojie He
[2]
Sheng Tang
[3]
Xiaofeng Lai
[4]
Jie Ren
[5]
XinCheng Yu
[6]
Jinhua Lin
[7]
Mohan Wang
[8]
Mariya M El Akkawi
[9]
Shan Zeng
[10]
Dingsheng Zha
journal
Frontiers in pharmacology
year
2022
abstract
Rheumatoid arthritis (RA) is a chronic, heterogeneous autoimmune disease with a high disability rate that seriously affects society and individuals. However, there is a lack of effective and reliable diagnostic markers and therapeutic targets. In this study, we identified diagnostic markers of RA based on RNA modification and explored its role as well as degree of immune cell infiltration. We used the gene expression profile data of three synovial tissues (GSE55235, GSE55457, GSE77298) from the Gene Expression Omnibus (GEO) database and the gene of 5 RNA modification genes (including m6A, m1A, m5C, APA, A-1), combined with cluster analysis, identified four RNA modifiers closely related to RA (YTHDC1, LRPPRC, NOP2, and CLP1) and five immune cells namely T cell CD8, CD4 memory resting, T cells regulatory (Tregs) Macrophages M0, and Neutrophils. Based on the LASSO regression algorithm, hub genes and immune cell prediction models were established respectively in RA and a nomogram based on the immune cell model was built. Around 4 key RNA modification regulator genes, miRNA-mRNA, mRNA-TF networks have been established, and GSEA-GO, KEGG-GSEA enrichment analysis has been carried out. Finally, CLP1 was established as an effective RA diagnostic marker, and was highly positively correlated with T cells follicular helper (Tfh) infiltration. On the other hand, highly negatively correlated with the expression of mast cells. In short, CLP1 may play a non-negligible role in the onset and development of RA by altering immune cell infiltration, and it is predicted to represent a novel target for RA clinical diagnosis and therapy.
claims array · 2 items
[0] object · 6 fields
id
claim-data-access
statement
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.
kind
methodological
target
null
evidence array · 1 item
[0] object · 3 fields
asset
source:pmid:35721104
locator
sections[25] "Data Availability Statement" paragraph 2
quote
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.
state
complete
[1] object · 6 fields
id
claim-target-result
statement
The immune correlation of diagnostic marker CLP1 was investigated, and the result demonstrated a significant positive correlation between the infiltration degree of B cells naïve, Dendritic cells activated, Eosinophils,Macrophages, Monocytes, Plasma cells,T cells CD8, and T cells follicular helper. of which, T cells follicular helper had the highest positive correlation (0.48), while mast cells, NK cells activated, and T cells CD4 memory infiltration revealed a significant negative correlation, with Mast cells having the highest negative correlation (-0.39) (Figure 14).
kind
qualitative
target
null
evidence array · 1 item
[0] object · 3 fields
asset
source:pmid:35721104
locator
sections[22] "Diagnostic Marker Analysis" paragraph 2
quote
The immune correlation of diagnostic marker CLP1 was investigated, and the result demonstrated a significant positive correlation between the infiltration degree of B cells naïve, Dendritic cells activated, Eosinophils,Macrophages, Monocytes, Plasma cells,T cells CD8, and T cells follicular helper. of which, T cells follicular helper had the highest positive correlation (0.48), while mast cells, NK cells activated, and T cells CD4 memory infiltration revealed a significant negative correlation, with Mast cells having the highest negative correlation (-0.39) (Figure 14).
state
complete
gaps array · 0 items
experiment object · 8 fields
state
partial
objective
The immune correlation of diagnostic marker CLP1 was investigated, and the result demonstrated a significant positive correlation between the infiltration degree of B cells naïve, Dendritic cells activated, Eosinophils,Macrophages, Monocytes, Plasma cells,T cells CD8, and T cells follicular helper. of which, T cells follicular helper had the highest positive correlation (0.48), while mast cells, NK cells activated, and T cells CD4 memory infiltration revealed a significant negative correlation, with Mast cells having the highest negative correlation (-0.39) (Figure 14).
steps array · 3 items
[0] object · 13 fields
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.
parameters object · 0 fields
inputs array · 1 item
[0]
source:pmid:35721104
outputs array · 1 item
[0]
the published estimate and its evidence
instruments array · 0 items
reagents array · 0 items
[1] object · 13 fields
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.
parameters object · 0 fields
inputs array · 1 item
[0]
data:geo:GSE55235
outputs array · 1 item
[0]
the source data with its repository provenance
instruments array · 0 items
reagents array · 0 items
[2] object · 13 fields
id
run_analysis
order
3
name
Run the published analysis
kind
analysis
state
blocked
blocked_on
method:group_comparison_wilcoxon
description
Apply the paper's statistical method to the resolved series and compare the result with the published target.
parameters object · 0 fields
inputs array · 1 item
[0]
data:geo:GSE55235
outputs array · 1 item
[0]
the replicated result and its comparison
instruments array · 0 items
reagents array · 0 items
materials array · 0 items
instruments array · 0 items
reagents array · 0 items
conditions object · 0 fields
gaps array · 1 item
[0]
step:run_analysis blocked on method:group_comparison_wilcoxon
data object · 3 fields
state
partial
assets array · 4 items
[0] object · 15 fields
id
source:pmid:35721104
role
manuscript
format
xml
media_type
application/xml
uri
https://doi.org/10.3389/fphar.2022.827215
sha256
sha256:6ba0ec2ac60350513e18bbd00aeb8eca91f281d6d389e70616f2cfb5e990fc75
bytes
55900
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
10.3389/fphar.2022.827215
version
null
note
Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.
structure object · 4 fields
pmcid
PMC9201986
source
europe_pmc_fulltext
coverage
whole_body
text_hash_scope
rendered_section_body
[1] object · 15 fields
id
data:geo:GSE55235
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=GSE55235
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE55235
version
null
note
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.
access_statement_kind
data_availability_statement
sample_accessions array · 30 items
[0]
GSM1332201
[1]
GSM1332202
[2]
GSM1332203
[3]
GSM1332204
[4]
GSM1332205
[5]
GSM1332206
[6]
GSM1332207
[7]
GSM1332208
[8]
GSM1332209
[9]
GSM1332210
[10]
GSM1332211
[11]
GSM1332212
[12]
GSM1332213
[13]
GSM1332214
[14]
GSM1332215
[15]
GSM1332216
[16]
GSM1332217
[17]
GSM1332218
[18]
GSM1332219
[19]
GSM1332220
[20]
GSM1332221
[21]
GSM1332222
[22]
GSM1332223
[23]
GSM1332224
[24]
GSM1332225
[25]
GSM1332226
[26]
GSM1332227
[27]
GSM1332228
[28]
GSM1332229
[29]
GSM1332230
sample_count
30
group_sizes
null
group_sizes_basis
null
platform
96
taxon
Homo sapiens
title
Identification of rheumatoid arthritis and osteoarthritis patients by transcriptome-based rule set generation
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[2] object · 15 fields
id
data:geo:GSE55457
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=GSE55457
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE55457
version
null
note
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.
access_statement_kind
data_availability_statement
sample_accessions array · 33 items
[0]
GSM1337304
[1]
GSM1337305
[2]
GSM1337306
[3]
GSM1337307
[4]
GSM1337308
[5]
GSM1337309
[6]
GSM1337310
[7]
GSM1337311
[8]
GSM1337312
[9]
GSM1337313
[10]
GSM1337314
[11]
GSM1337315
[12]
GSM1337316
[13]
GSM1337317
[14]
GSM1337318
[15]
GSM1337319
[16]
GSM1337320
[17]
GSM1337321
[18]
GSM1337322
[19]
GSM1337323
[20]
GSM1337324
[21]
GSM1337325
[22]
GSM1337326
[23]
GSM1337327
[24]
GSM1337328
[25]
GSM1337329
[26]
GSM1337330
[27]
GSM1337331
[28]
GSM1337332
[29]
GSM1337333
[30]
GSM1337334
[31]
GSM1337335
[32]
GSM1337336
sample_count
33
group_sizes
null
group_sizes_basis
null
platform
96
taxon
Homo sapiens
title
Identification of rheumatoid arthritis and osteoarthritis patients by transcriptome-based rule set generation [Jena]
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[3] object · 15 fields
id
data:geo:GSE77298
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=GSE77298
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE77298
version
null
note
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.
access_statement_kind
data_availability_statement
sample_accessions array · 23 items
[0]
GSM2048265
[1]
GSM2048266
[2]
GSM2048267
[3]
GSM2048268
[4]
GSM2048269
[5]
GSM2048270
[6]
GSM2048271
[7]
GSM2048272
[8]
GSM2048273
[9]
GSM2048274
[10]
GSM2048275
[11]
GSM2048276
[12]
GSM2048277
[13]
GSM2048278
[14]
GSM2048279
[15]
GSM2048280
[16]
GSM2048281
[17]
GSM2048282
[18]
GSM2048283
[19]
GSM2048284
[20]
GSM2048285
[21]
GSM2048286
[22]
GSM2048287
sample_count
23
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Synovial biopsies of rheumatoid arthritis and healthy controls
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 · 6 items
[0]
asset:data:geo:GSE55235 not downloaded
[1]
asset:data:geo:GSE55235 licence not read
[2]
asset:data:geo:GSE55457 not downloaded
[3]
asset:data:geo:GSE55457 licence not read
[4]
asset:data:geo:GSE77298 not downloaded
[5]
asset:data:geo:GSE77298 licence not read
analysis object · 4 fields
state
partial
methods array · 5 items
[0] object · 10 fields
id
method-1
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
1
band
reordered
quote
DEG is recognized and integrated by the Limma package (Ritchie et al., 2015) and FunRich software (Pathan et al., 2015) in R, we set the genes with logFC>1 and adjPvalue<0.05 as up-regulated genes. CIBERSORT algorithm was used to analyze the immune infiltration between the rheumatoid and normal tissues, to identify the immune cells that were differentially enriched between the diseased and normal tissues in the two sets of data, to calculate the Pearson correlation coefficient between the expression level of key genes and immune cells, and to evaluate the relationship between the key genes and the immune infiltration level. LASSO regression analysis in the R glmnet package (Friedman et al., 2010) was performed on the training set. To avoid overfitting the model design of the training set, tenfold cross validation is performed. The differences between the non-normally distributed variables were analyzed using the Mann-Whitney U test (i.e. Wilcoxon rank-sum test).
[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 t-test
[2] object · 10 fields
id
method-3
family
group_comparison
specific
mann_whitney
label
Group comparison
dsl_operations array · 0 items
missing_operations array · 1 item
[0]
group_comparison_mann_whitney
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
Mann-Whitney
[3] object · 10 fields
id
method-4
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
0.8
band
high
quote
limma
[4] object · 10 fields
id
method-5
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
targets array · 0 items
gaps array · 1 item
[0]
method.group_comparison_wilcoxon
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
false
required_operations array · 0 items
missing_operations array · 1 item
[0]
group_comparison_wilcoxon
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: wilcoxon.
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]
GSE55235
[1]
GSE55457
[2]
GSE77298
resolved_accessions array · 3 items
[0]
GSE55235
[1]
GSE55457
[2]
GSE77298
statements array · 1 item
[0]
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.
basis
The paper names GSE55235, GSE55457, GSE77298 in Gene Expression Omnibus (GEO) database and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 0 items
assets array · 2 items
[0]
source:pmid:35721104
[1]
data:geo:GSE55235
steps array · 0 items
must_build object · 5 fields
dsl_operations array · 1 item
[0] object · 3 fields
operation
group_comparison_wilcoxon
priority
null
converters array · 0 items
readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
[0]
data:geo:GSE55235
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
2026-11-01T17:51:24Z
independence
single_reader
evidence_check object · 2 fields
method
reordered
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
15722
completion_tokens
2604
cached_tokens
128
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:35721104
type
paper
label
pmid:35721104
[1] object · 3 fields
id
source:pmid:35721104
type
manuscript
label
PMID 35721104 full text
[2] object · 3 fields
id
data:geo:GSE55235
type
dataset
label
GEO GSE55235
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:35721104
type
paper
label
pmid:35721104
[1] object · 3 fields
id
source:pmid:35721104
type
manuscript
label
PMID 35721104 full text
[2] object · 3 fields
id
data:geo:GSE55235
type
dataset
label
GEO GSE55235
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-35721104
type
extraction
used array · 1 item
[0]
source:pmid:35721104
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE55235
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE55235
agent
agent:corpus-assay-engine
agents array · 2 items
[0] object · 3 fields
id
agent:corpus-assay-engine
type
software
label
Corpus assay engine
[1] object · 3 fields
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 object · 4 fields
parent_id
pmid:35721104
parent_hash
sha256:d0e3dd24476201be1fc1cb48e1fcee4a89947af3deaab3cae99db7188b7c0ed9
fork_of
null
gaps array · 12 items
[0]
asset:data:geo:GSE55235 licence not read
[1]
asset:data:geo:GSE55235 not downloaded
[2]
asset:data:geo:GSE55457 licence not read
[3]
asset:data:geo:GSE55457 not downloaded
[4]
asset:data:geo:GSE77298 licence not read
[5]
asset:data:geo:GSE77298 not downloaded
[6]
execution.not_run
[7]
method.group_comparison_wilcoxon
[8]
review.human_critique
[9]
review.independent_reader
[10]
review.machine_critique
[11]
step:run_analysis blocked on method:group_comparison_wilcoxon
assays array · 2 items
[0] object · 11 fields
role
data_generation
definition_id
animal_model
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.85
evidence array · 1 item
[0]
ommonly highly expressed in RA, joint damage in mice with collagen-induced arthritis was signific
order_basis
paper_text_order:7811
id
assay:1
[1] object · 11 fields
role
analysis
definition_id
group_comparison
definition_version
f2132e96ae6c7a4e
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
DEG is recognized and integrated by the Limma package (Ritchie et al., 2015) and FunRich software (Pathan et al., 2015) in R, we set the genes with logFC>1 and adjPvalue<0.05 as up-regulated genes. CIBERSORT algorithm was used to analyze the immune infiltration between the rheumatoid and normal tissues, to identify the immune cells that were differentially enriched between the diseased and normal tissues in the two sets of data, to calculate the Pearson correlation coefficient between the expression level of key genes and immune cells, and to evaluate the relationship between the key genes and the immune infiltration level. LASSO regression analysis in the R glmnet package (Friedman et al., 2010) was performed on the training set. To avoid overfitting the model design of the training set, tenfold cross validation is performed. The differences between the non-normally distributed variables were analyzed using the Mann-Whitney U test (i.e. Wilcoxon rank-sum test).
order_basis
consumes_earlier_output
id
assay:2
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35721104", "kind": "science-record", "revision": 5, "content_hash": "sha256:2e15f9b6d6336ad65a7165961ffd82448db18bf2045debf9ad061afc652311ef", "created_at": "2026-11-01T18:14:43Z", "updated_at": "2026-11-01T22:49:21Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "CLP1 is a Prognosis-Related Biomarker and Correlates With Immune Infiltrates in Rheumatoid Arthritis.", "doi": "10.3389/fphar.2022.827215", "pmid": "35721104", "authors": ["Zhenyu Zhao", "Shaojie He", "Sheng Tang", "Xiaofeng Lai", "Jie Ren", "XinCheng Yu", "Jinhua Lin", "Mohan Wang", "Mariya M El Akkawi", "Shan Zeng", "Dingsheng Zha"], "journal": "Frontiers in pharmacology", "year": 2022, "abstract": "Rheumatoid arthritis (RA) is a chronic, heterogeneous autoimmune disease with a high disability rate that seriously affects society and individuals. However, there is a lack of effective and reliable diagnostic markers and therapeutic targets. In this study, we identified diagnostic markers of RA based on RNA modification and explored its role as well as degree of immune cell infiltration. We used the gene expression profile data of three synovial tissues (GSE55235, GSE55457, GSE77298) from the Gene Expression Omnibus (GEO) database and the gene of 5 RNA modification genes (including m6A, m1A, m5C, APA, A-1), combined with cluster analysis, identified four RNA modifiers closely related to RA (YTHDC1, LRPPRC, NOP2, and CLP1) and five immune cells namely T cell CD8, CD4 memory resting, T cells regulatory (Tregs) Macrophages M0, and Neutrophils. Based on the LASSO regression algorithm, hub genes and immune cell prediction models were established respectively in RA and a nomogram based on the immune cell model was built. Around 4 key RNA modification regulator genes, miRNA-mRNA, mRNA-TF networks have been established, and GSEA-GO, KEGG-GSEA enrichment analysis has been carried out. Finally, CLP1 was established as an effective RA diagnostic marker, and was highly positively correlated with T cells follicular helper (Tfh) infiltration. On the other hand, highly negatively correlated with the expression of mast cells. In short, CLP1 may play a non-negligible role in the onset and development of RA by altering immune cell infiltration, and it is predicted to represent a novel target for RA clinical diagnosis and therapy.", "claims": [{"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35721104", "locator": "sections[25] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The immune correlation of diagnostic marker CLP1 was investigated, and the result demonstrated a significant positive correlation between the infiltration degree of B cells naïve, Dendritic cells activated, Eosinophils,Macrophages, Monocytes, Plasma cells,T cells CD8, and T cells follicular helper. of which, T cells follicular helper had the highest positive correlation (0.48), while mast cells, NK cells activated, and T cells CD4 memory infiltration revealed a significant negative correlation, with Mast cells having the highest negative correlation (-0.39) (Figure 14).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35721104", "locator": "sections[22] \"Diagnostic Marker Analysis\" paragraph 2", "quote": "The immune correlation of diagnostic marker CLP1 was investigated, and the result demonstrated a significant positive correlation between the infiltration degree of B cells naïve, Dendritic cells activated, Eosinophils,Macrophages, Monocytes, Plasma cells,T cells CD8, and T cells follicular helper. of which, T cells follicular helper had the highest positive correlation (0.48), while mast cells, NK cells activated, and T cells CD4 memory infiltration revealed a significant negative correlation, with Mast cells having the highest negative correlation (-0.39) (Figure 14)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The immune correlation of diagnostic marker CLP1 was investigated, and the result demonstrated a significant positive correlation between the infiltration degree of B cells naïve, Dendritic cells activated, Eosinophils,Macrophages, Monocytes, Plasma cells,T cells CD8, and T cells follicular helper. of which, T cells follicular helper had the highest positive correlation (0.48), while mast cells, NK cells activated, and T cells CD4 memory infiltration revealed a significant negative correlation, with Mast cells having the highest negative correlation (-0.39) (Figure 14).", "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:35721104"], "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:GSE55235"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "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:GSE55235"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35721104", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fphar.2022.827215", "sha256": "sha256:6ba0ec2ac60350513e18bbd00aeb8eca91f281d6d389e70616f2cfb5e990fc75", "bytes": 55900, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fphar.2022.827215", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9201986", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE55235", "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=GSE55235", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE55235", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1332201", "GSM1332202", "GSM1332203", "GSM1332204", "GSM1332205", "GSM1332206", "GSM1332207", "GSM1332208", "GSM1332209", "GSM1332210", "GSM1332211", "GSM1332212", "GSM1332213", "GSM1332214", "GSM1332215", "GSM1332216", "GSM1332217", "GSM1332218", "GSM1332219", "GSM1332220", "GSM1332221", "GSM1332222", "GSM1332223", "GSM1332224", "GSM1332225", "GSM1332226", "GSM1332227", "GSM1332228", "GSM1332229", "GSM1332230"], "sample_count": 30, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Identification of rheumatoid arthritis and osteoarthritis patients by transcriptome-based rule set generation", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE55457", "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=GSE55457", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE55457", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1337304", "GSM1337305", "GSM1337306", "GSM1337307", "GSM1337308", "GSM1337309", "GSM1337310", "GSM1337311", "GSM1337312", "GSM1337313", "GSM1337314", "GSM1337315", "GSM1337316", "GSM1337317", "GSM1337318", "GSM1337319", "GSM1337320", "GSM1337321", "GSM1337322", "GSM1337323", "GSM1337324", "GSM1337325", "GSM1337326", "GSM1337327", "GSM1337328", "GSM1337329", "GSM1337330", "GSM1337331", "GSM1337332", "GSM1337333", "GSM1337334", "GSM1337335", "GSM1337336"], "sample_count": 33, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Identification of rheumatoid arthritis and osteoarthritis patients by transcriptome-based rule set generation [Jena]", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE77298", "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=GSE77298", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE77298", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2048265", "GSM2048266", "GSM2048267", "GSM2048268", "GSM2048269", "GSM2048270", "GSM2048271", "GSM2048272", "GSM2048273", "GSM2048274", "GSM2048275", "GSM2048276", "GSM2048277", "GSM2048278", "GSM2048279", "GSM2048280", "GSM2048281", "GSM2048282", "GSM2048283", "GSM2048284", "GSM2048285", "GSM2048286", "GSM2048287"], "sample_count": 23, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Synovial biopsies of rheumatoid arthritis and healthy controls", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE55235 not downloaded", "asset:data:geo:GSE55235 licence not read", "asset:data:geo:GSE55457 not downloaded", "asset:data:geo:GSE55457 licence not read", "asset:data:geo:GSE77298 not downloaded", "asset:data:geo:GSE77298 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "reordered", "quote": "DEG is recognized and integrated by the Limma package (Ritchie et al., 2015) and FunRich software (Pathan et al., 2015) in R, we set the genes with logFC>1 and adjPvalue<0.05 as up-regulated genes. CIBERSORT algorithm was used to analyze the immune infiltration between the rheumatoid and normal tissues, to identify the immune cells that were differentially enriched between the diseased and normal tissues in the two sets of data, to calculate the Pearson correlation coefficient between the expression level of key genes and immune cells, and to evaluate the relationship between the key genes and the immune infiltration level. LASSO regression analysis in the R glmnet package (Friedman et al., 2010) was performed on the training set. To avoid overfitting the model design of the training set, tenfold cross validation is performed. The differences between the non-normally distributed variables were analyzed using the Mann-Whitney U test (i.e. Wilcoxon rank-sum test)."}}, {"id": "method-2", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Student t-test"}}, {"id": "method-3", "family": "group_comparison", "specific": "mann_whitney", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_mann_whitney"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Mann-Whitney"}}, {"id": "method-4", "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": 0.8, "band": "high", "quote": "limma"}}, {"id": "method-5", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Pearson correlation"}}], "targets": [], "gaps": ["method.group_comparison_wilcoxon"]}, "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": false, "required_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: wilcoxon."}, "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": ["GSE55235", "GSE55457", "GSE77298"], "resolved_accessions": ["GSE55235", "GSE55457", "GSE77298"], "statements": ["The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors."], "basis": "The paper names GSE55235, GSE55457, GSE77298 in Gene Expression Omnibus (GEO) database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:35721104", "data:geo:GSE55235"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "group_comparison_wilcoxon", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE55235"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:51:24Z", "independence": "single_reader"}, "evidence_check": {"method": "reordered", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 15722, "completion_tokens": 2604, "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:35721104", "type": "paper", "label": "pmid:35721104"}, {"id": "source:pmid:35721104", "type": "manuscript", "label": "PMID 35721104 full text"}, {"id": "data:geo:GSE55235", "type": "dataset", "label": "GEO GSE55235"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35721104", "type": "paper", "label": "pmid:35721104"}, {"id": "source:pmid:35721104", "type": "manuscript", "label": "PMID 35721104 full text"}, {"id": "data:geo:GSE55235", "type": "dataset", "label": "GEO GSE55235"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35721104", "type": "extraction", "used": ["source:pmid:35721104"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE55235", "type": "accession_resolution", "used": ["data:geo:GSE55235"], "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:35721104", "parent_hash": "sha256:d0e3dd24476201be1fc1cb48e1fcee4a89947af3deaab3cae99db7188b7c0ed9", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE55235 licence not read", "asset:data:geo:GSE55235 not downloaded", "asset:data:geo:GSE55457 licence not read", "asset:data:geo:GSE55457 not downloaded", "asset:data:geo:GSE77298 licence not read", "asset:data:geo:GSE77298 not downloaded", "execution.not_run", "method.group_comparison_wilcoxon", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:group_comparison_wilcoxon"], "assays": [{"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["ommonly highly expressed in RA, joint damage in mice with collagen-induced arthritis was signific"], "order_basis": "paper_text_order:7811", "id": "assay:1"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["DEG is recognized and integrated by the Limma package (Ritchie et al., 2015) and FunRich software (Pathan et al., 2015) in R, we set the genes with logFC>1 and adjPvalue<0.05 as up-regulated genes. CIBERSORT algorithm was used to analyze the immune infiltration between the rheumatoid and normal tissues, to identify the immune cells that were differentially enriched between the diseased and normal tissues in the two sets of data, to calculate the Pearson correlation coefficient between the expression level of key genes and immune cells, and to evaluate the relationship between the key genes and the immune infiltration level. LASSO regression analysis in the R glmnet package (Friedman et al., 2010) was performed on the training set. To avoid overfitting the model design of the training set, tenfold cross validation is performed. The differences between the non-normally distributed variables were analyzed using the Mann-Whitney U test (i.e. Wilcoxon rank-sum test)."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}