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pmid:33343487

Development and Validation of a Five-Gene Signature to Predict Relapse-Free Survival in Multiple Sclerosis.

Fei Ye · Jie Liang · Jiaoxing Li · Haiyan Li · Wenli Sheng

Frontiers in neurology · 2020 doi:10.3389/fneur.2020.579683

Paper

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Experiment

complete

Data

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partial

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title
Development and Validation of a Five-Gene Signature to Predict Relapse-Free Survival in Multiple Sclerosis.
doi
10.3389/fneur.2020.579683
pmid
33343487
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[0]
Fei Ye
[1]
Jie Liang
[2]
Jiaoxing Li
[3]
Haiyan Li
[4]
Wenli Sheng
journal
Frontiers in neurology
year
2020
abstract
Background: Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system with a variable natural history of relapse and remission. Previous studies have found many differentially expressed genes (DEGs) in the peripheral blood of MS patients and healthy controls, but the value of these genes for predicting the risk of relapse remains elusive. Here we develop and validate an effective and noninvasive gene signature for predicting relapse-free survival (RFS) in MS patients. Methods: Gene expression matrices were downloaded from Gene Expression Omnibus and ArrayExpress. DEGs in MS patients and healthy controls were screened in an integrated analysis of seven data sets. Candidate genes from a combination of protein-protein interaction and weighted correlation network analysis were used to identify key genes related to RFS. An independent data set (GSE15245) was randomized into training and test groups. Univariate and least absolute shrinkage and selection operator-Cox regression analyses were used in the training group to develop a gene signature. A nomogram incorporating independent risk factors was developed via multivariate Cox regression analyses. Kaplan-Meier methods, receiver-operating characteristic (ROC) curves, and Harrell's concordance index (C-index) were used to estimate the performance of the gene signature and nomogram. The test group was used for external validation. Results: A five-gene signature comprising FTH1, GBP2, MYL6, NCOA4, and SRP9 was used to calculate risk scores to predict individual RFS. The risk score was an independent risk factor, and a nomogram incorporating clinical parameters was established. ROC curves and C-indices demonstrated great performance of these predictive tools in both the training and test groups. Conclusions: The five-gene signature may be a reliable tool for assisting physicians in predicting RFS in clinical practice. We anticipate that these findings could not only facilitate personalized treatment for MS patients but also provide insight into the complex molecular mechanism of this disease.
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Prediction of acute multiple sclerosis relapses by transcription levels of peripheral blood cells
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GSM1027037
[45]
GSM1027038
[46]
GSM1027039
[47]
GSM1027040
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GSM1027041
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GSM1027042
[50]
GSM1027043
[51]
GSM1027044
[52]
GSM1027045
[53]
GSM1027046
[54]
GSM1027047
[55]
GSM1027048
[56]
GSM1027049
[57]
GSM1027050
[58]
GSM1027051
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GSM1027052
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GSM1027053
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GSM1027054
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GSM1027055
[63]
GSM1027056
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GSM1027057
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GSM1027058
[66]
GSM1027059
[67]
GSM1027060
sample_count
68
group_sizes
null
group_sizes_basis
null
platform
6244
taxon
Homo sapiens
title
Expression data from multiple sclerosis patients in remission and relapse
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[8] object · 15 fields
id
data:geo:GSE59085
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=GSE59085
sha256
null
bytes
null
access
open
state
resolved
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null
reader_status
reader_required
identifier
GSE59085
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null
note
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.
access_statement_kind
data_availability_statement
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GSM1426343
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GSM1426352
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GSM1426355
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GSM1426356
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GSM1426359
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GSM1426360
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GSM1426361
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GSM1426362
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GSM1426363
[21]
GSM1426364
sample_count
22
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
The Role of Interleukin-11 in the Development of the Autoimmune Response in Multiple Sclerosis
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
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asset:table:pmid:33343487:1
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jats-table
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section[3]/table-wrap[1]#T1
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null
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Summary of seven microarray data sets that met the inclusive criteria in this study.
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pmcid
PMC7744728
section_index
3
section_title
Data Downloading and Processing
row_count
9
column_count
6
table object · 8 fields
label
Table 1
caption
Summary of seven microarray data sets that met the inclusive criteria in this study.
rows array · 9 items
[0] array · 5 items
[0]
Accession
[1]
Released date
[2]
Platform
[3]
Source
[4]
Samples
[1] array · 6 items
[0]
[1]
[2]
[3]
[4]
Healthy control
[5]
Multiple sclerosis
[2] array · 6 items
[0]
E-MTAB-69
[1]
Dec 2, 2009
[2]
A-AFFY-44
[3]
PBMC
[4]
18
[5]
26
[3] array · 6 items
[0]
E-MTAB-4890
[1]
Sep 30, 2017
[2]
A-MEXP-931
[3]
PBMC
[4]
40
[5]
142 (49 RRMS, 21 SPMS, 23 PPMS, 49 CIS)
[4] array · 6 items
[0]
E-MTAB-5151
[1]
Sep 30, 2017
[2]
A-MEXP-931
[3]
PBMC
[4]
27
[5]
49 (21 RRMS, 13 SPMS, 23 PPMS)
[5] array · 6 items
[0]
GSE17048
[1]
Jul 10, 2009
[2]
GPL6947
[3]
Blood
[4]
45
[5]
99 (36 RRMS, 20 SPMS, 43 PPMS)
[6] array · 6 items
[0]
GSE21942
[1]
May 20, 2010
[2]
GPL570
[3]
PBMC
[4]
15
[5]
14
[7] array · 6 items
[0]
GSE41890
[1]
Oct 28, 2012
[2]
GPL6244
[3]
PBMC
[4]
24
[5]
44
[8] array · 6 items
[0]
GSE59085
[1]
Jul 3, 2014
[2]
GPL570
[3]
PBMC
[4]
7
[5]
15 (15 CIS)
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section[3]/table-wrap[1]#T1
[10] object · 16 fields
id
asset:table:pmid:33343487:2
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table
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jats-table
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application/vnd.jats.table+json
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null
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read_table
reader_status
available
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section[15]/table-wrap[1]#T2
version
null
note
The clinical features of MS patients in the training group and test group.
structure object · 5 fields
pmcid
PMC7744728
section_index
15
section_title
Identification of Key Genes Related to RFS and Construction of a Predictive Gene Signature
row_count
11
column_count
4
table object · 8 fields
label
Table 2
caption
The clinical features of MS patients in the training group and test group.
rows array · 11 items
[0] array · 4 items
[0]
Feature
[1]
Training (n = 63)
[2]
Test (n = 31)
[3]
p
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[0]
Age (years)
[2] array · 4 items
[0]
18–50
[1]
53 (84.1%)
[2]
28 (90.3%)
[3]
0.413
[3] array · 4 items
[0]
>50
[1]
10 (15.9%)
[2]
3 (9.7%)
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[4] array · 4 items
[0]
Female
[1]
41 (65.1%)
[2]
19 (61.3%)
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0.719
[5] array · 1 item
[0]
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[6] array · 4 items
[0]
CIS
[1]
19 (30.2%)
[2]
13 (41.9%)
[3]
0.257
[7] array · 4 items
[0]
MS
[1]
44 (69.8%)
[2]
18 (58.1%)
[3]
[8] array · 4 items
[0]
DMT
[1]
16 (25.4%)
[2]
13 (41.9%)
[3]
0.103
[9] array · 4 items
[0]
Follow-up (years)
[1]
2.0 ± 1.3
[2]
1.9 ± 1.3
[3]
0.182
[10] array · 4 items
[0]
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[1]
43 (68.3%)
[2]
21 (67.7%)
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0.960
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section[15]/table-wrap[1]#T2
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[0]
asset:data:geo:E-MTAB-4890 not downloaded
[1]
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[3]
asset:data:geo:E-MTAB-5151 licence not read
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[5]
asset:data:geo:E-MTAB-69 licence not read
[6]
asset:data:geo:GSE15245 not downloaded
[7]
asset:data:geo:GSE15245 licence not read
[8]
asset:data:geo:GSE17048 not downloaded
[9]
asset:data:geo:GSE17048 licence not read
[10]
asset:data:geo:GSE21942 not downloaded
[11]
asset:data:geo:GSE21942 licence not read
[12]
asset:data:geo:GSE41890 not downloaded
[13]
asset:data:geo:GSE41890 licence not read
[14]
asset:data:geo:GSE59085 not downloaded
[15]
asset:data:geo:GSE59085 licence not read
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state
partial
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[0] object · 10 fields
id
method-1
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survival_analysis
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kaplan_meier
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Survival analysis
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survival_km
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data_shapes array · 1 item
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time_to_event_with_censoring
evidence object · 3 fields
score
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Kaplan-Meier
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id
method-2
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survival_analysis
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Survival analysis
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cox_ph
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time_to_event_with_censoring
evidence object · 3 fields
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Cox regression
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method-3
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network_analysis
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Network / pathway analysis
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build_graph
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centrality_scores
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edge_list
evidence object · 3 fields
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protein-protein interaction
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method-4
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null
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missing_operations array · 0 items
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data_shapes array · 0 items
evidence object · 3 fields
score
1
band
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“An integrated data set was obtained with batch normalization.”
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gaps array · 1 item
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method.reader_named_unmapped
capability object · 3 fields
state
complete
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[0] object · 6 fields
capability_id
capability:computational_analysis
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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]
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differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
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state
complete
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blocked_on
nothing:replicable_now
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survival_km
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The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier.
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tier
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capability:computational_analysis
availability_state
owned
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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
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[0]
GSE17048
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GSE21942
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GSE41890
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GSE59085
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E-MTAB-69
[5]
E-MTAB-4890
[6]
E-MTAB-5151
[7]
GSE15245
resolved_accessions array · 8 items
[0]
GSE17048
[1]
GSE21942
[2]
GSE41890
[3]
GSE59085
[4]
E-MTAB-69
[5]
E-MTAB-4890
[6]
E-MTAB-5151
[7]
GSE15245
statements array · 1 item
[0]
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.
basis
The paper names GSE17048, GSE21942, GSE41890, GSE59085, E-MTAB-69, E-MTAB-4890, E-MTAB-5151, GSE15245 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 · 1 item
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survival_km
assets array · 4 items
[0]
source:pmid:33343487
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data:geo:E-MTAB-4890
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asset:table:pmid:33343487:1
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asset:table:pmid:33343487:2
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run_analysis
must_build object · 5 fields
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data:geo:E-MTAB-4890
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review object · 5 fields
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partial
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MiniMax-M3.1-Flash
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minimax
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minimax
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2026-10-31T18:25:38Z
independence
single_reader
evidence_check object · 2 fields
method
reordered
availability
verbatim
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3
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22756
completion_tokens
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cached_tokens
7688
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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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minimax
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review.independent_reader
[1]
review.machine_critique
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review.human_critique
execution object · 5 fields
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absent
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not_run
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null
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gaps array · 1 item
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execution.not_run
provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:33343487
type
paper
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pmid:33343487
[1] object · 3 fields
id
source:pmid:33343487
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manuscript
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PMID 33343487 full text
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id
data:geo:E-MTAB-4890
type
dataset
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GEO E-MTAB-4890
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id
activity-reading-sci-2026-11-01
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id
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id
source:pmid:33343487
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PMID 33343487 full text
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id
data:geo:E-MTAB-4890
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dataset
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GEO E-MTAB-4890
agent
agent:corpus-assay-engine
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id
activity-read-33343487
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extraction
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[0]
source:pmid:33343487
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agent:minimax-reader
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id
activity-resolve-E-MTAB-4890
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accession_resolution
used array · 1 item
[0]
data:geo:E-MTAB-4890
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agent:corpus-assay-engine
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id
agent:corpus-assay-engine
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software
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Corpus assay engine
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agent:minimax-reader
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MiniMax literature reader
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dsl_catalogue_fingerprint
343fb30756ba6ec3
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2cb3e42f047d2ecf
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lineage object · 4 fields
parent_id
pmid:33343487
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sha256:31920e36b7baba766bbafc84559a1fb3df63a441ce281e6ae0759a9e2e8a2beb
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asset:data:geo:E-MTAB-4890 licence not read
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[7]
asset:data:geo:GSE15245 not downloaded
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[9]
asset:data:geo:GSE17048 not downloaded
[10]
asset:data:geo:GSE21942 licence not read
[11]
asset:data:geo:GSE21942 not downloaded
[12]
asset:data:geo:GSE41890 licence not read
[13]
asset:data:geo:GSE41890 not downloaded
[14]
asset:data:geo:GSE59085 licence not read
[15]
asset:data:geo:GSE59085 not downloaded
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execution.not_run
[17]
method.reader_named_unmapped
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review.human_critique
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review.independent_reader
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analysis
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survival_analysis
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f2132e96ae6c7a4e
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survival_km
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supported
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dsl_catalogue
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:33343487", "kind": "science-record", "revision": 5, "content_hash": "sha256:e82bc25e8c1ace87475f1258e0c9d65848e68e1b86e5d49f701388ab33e1e7f6", "created_at": "2026-11-01T15:41:20Z", "updated_at": "2026-11-01T22:02:47Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Development and Validation of a Five-Gene Signature to Predict Relapse-Free Survival in Multiple Sclerosis.", "doi": "10.3389/fneur.2020.579683", "pmid": "33343487", "authors": ["Fei Ye", "Jie Liang", "Jiaoxing Li", "Haiyan Li", "Wenli Sheng"], "journal": "Frontiers in neurology", "year": 2020, "abstract": "Background: Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system with a variable natural history of relapse and remission. Previous studies have found many differentially expressed genes (DEGs) in the peripheral blood of MS patients and healthy controls, but the value of these genes for predicting the risk of relapse remains elusive. Here we develop and validate an effective and noninvasive gene signature for predicting relapse-free survival (RFS) in MS patients. Methods: Gene expression matrices were downloaded from Gene Expression Omnibus and ArrayExpress. DEGs in MS patients and healthy controls were screened in an integrated analysis of seven data sets. Candidate genes from a combination of protein-protein interaction and weighted correlation network analysis were used to identify key genes related to RFS. An independent data set (GSE15245) was randomized into training and test groups. Univariate and least absolute shrinkage and selection operator-Cox regression analyses were used in the training group to develop a gene signature. A nomogram incorporating independent risk factors was developed via multivariate Cox regression analyses. Kaplan-Meier methods, receiver-operating characteristic (ROC) curves, and Harrell's concordance index (C-index) were used to estimate the performance of the gene signature and nomogram. The test group was used for external validation. Results: A five-gene signature comprising FTH1, GBP2, MYL6, NCOA4, and SRP9 was used to calculate risk scores to predict individual RFS. The risk score was an independent risk factor, and a nomogram incorporating clinical parameters was established. ROC curves and C-indices demonstrated great performance of these predictive tools in both the training and test groups. Conclusions: The five-gene signature may be a reliable tool for assisting physicians in predicting RFS in clinical practice. We anticipate that these findings could not only facilitate personalized treatment for MS patients but also provide insight into the complex molecular mechanism of this disease.", "claims": [{"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33343487", "locator": "sections[21] \"Data Availability Statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:33343487"], "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. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE17048", "GSE21942", "GSE41890", "GSE59085", "E-MTAB-69", "E-MTAB-4890", "E-MTAB-5151", "GSE15245"], "resolved_accessions": ["GSE17048", "GSE21942", "GSE41890", "GSE59085", "E-MTAB-69", "E-MTAB-4890", "E-MTAB-5151", "GSE15245"], "statements": ["The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."], "basis": "The paper names GSE17048, GSE21942, GSE41890, GSE59085, E-MTAB-69, E-MTAB-4890, E-MTAB-5151, GSE15245 in Gene Expression Omnibus (GEO) 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:33343487", "data:geo:E-MTAB-4890", "asset:table:pmid:33343487:1", "asset:table:pmid:33343487:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:E-MTAB-4890"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:25:38Z", "independence": "single_reader"}, "evidence_check": {"method": "reordered", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 22756, "completion_tokens": 3044, "cached_tokens": 7688}}, "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:33343487", "type": "paper", "label": "pmid:33343487"}, {"id": "source:pmid:33343487", "type": "manuscript", "label": "PMID 33343487 full text"}, {"id": "data:geo:E-MTAB-4890", "type": "dataset", "label": "GEO E-MTAB-4890"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33343487", "type": "paper", "label": "pmid:33343487"}, {"id": "source:pmid:33343487", "type": "manuscript", "label": "PMID 33343487 full text"}, {"id": "data:geo:E-MTAB-4890", "type": "dataset", "label": "GEO E-MTAB-4890"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33343487", "type": "extraction", "used": ["source:pmid:33343487"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-E-MTAB-4890", "type": "accession_resolution", "used": ["data:geo:E-MTAB-4890"], "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:33343487", "parent_hash": "sha256:31920e36b7baba766bbafc84559a1fb3df63a441ce281e6ae0759a9e2e8a2beb", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:E-MTAB-4890 licence not read", "asset:data:geo:E-MTAB-4890 not downloaded", "asset:data:geo:E-MTAB-5151 licence not read", "asset:data:geo:E-MTAB-5151 not downloaded", "asset:data:geo:E-MTAB-69 licence not read", "asset:data:geo:E-MTAB-69 not downloaded", "asset:data:geo:GSE15245 licence not read", "asset:data:geo:GSE15245 not downloaded", "asset:data:geo:GSE17048 licence not read", "asset:data:geo:GSE17048 not downloaded", "asset:data:geo:GSE21942 licence not read", "asset:data:geo:GSE21942 not downloaded", "asset:data:geo:GSE41890 licence not read", "asset:data:geo:GSE41890 not downloaded", "asset:data:geo:GSE59085 licence not read", "asset:data:geo:GSE59085 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": 0.7, "evidence": ["Kaplan-Meier"], "order_basis": "analysis_only", "id": "assay:1"}]}