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pmid:36338988

Machine learning-based characterization of cuprotosis-related biomarkers and immune infiltration in Parkinson's disease.

Songyun Zhao · Li Zhang · Wei Ji · Yachen Shi · Guichuan Lai · Hao Chi · Weiyi Huang · Chao Cheng

Frontiers in genetics · 2022 doi:10.3389/fgene.2022.1010361

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Experiment

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Data

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Analysis

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title
Machine learning-based characterization of cuprotosis-related biomarkers and immune infiltration in Parkinson's disease.
doi
10.3389/fgene.2022.1010361
pmid
36338988
authors array · 8 items
[0]
Songyun Zhao
[1]
Li Zhang
[2]
Wei Ji
[3]
Yachen Shi
[4]
Guichuan Lai
[5]
Hao Chi
[6]
Weiyi Huang
[7]
Chao Cheng
journal
Frontiers in genetics
year
2022
abstract
Background: Parkinson's disease (PD) is a neurodegenerative disease commonly seen in the elderly. On the other hand, cuprotosis is a new copper-dependent type of cell death that can be observed in various diseases. Methods: This study aimed to identify potential novel biomarkers of Parkinson's disease by biomarker analysis and to explore immune cell infiltration during the onset of cuprotosis. Gene expression profiles were retrieved from the GEO database for the GSE8397, GSE7621, GSE20163, and GSE20186 datasets. Three machine learning algorithms: the least absolute shrinkage and selection operator (LASSO), random forest, and support vector machine-recursive feature elimination (SVM-RFE) were used to screen for signature genes for Parkinson's disease onset and cuprotosis-related genes (CRG). Immune cell infiltration was estimated by ssGSEA, and cuprotosis-related genes associated with immune cells and immune function were examined using spearman correlation analysis. Nomogram was created to validate the accuracy of these cuprotosis-related genes in predicting PD disease progression. Classification of Parkinson's specimens using consensus clustering methods. Result: Three PD datasets from the Gene Expression Omnibus (GEO) database were combined after eliminating batch effects. By ssGSEA, we identified three cuprotosis-related genes ATP7A, SLC31A1, and DBT associated with immune cells or immune function in PD and more accurate for the diagnosis of Parkinson's disease course. Patients could benefit clinically from a characteristic line graph based on these genes. Consistent clustering analysis identified two subtypes, with the C2 subtype exhibiting higher immune cell infiltration and immune function. Conclusion: In conclusion, our study reveals that several newly identified cuprotosis-related genes intervene in the progression of Parkinson's disease through immune cell infiltration.
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Three machine learning algorithms: LASSO regression analysis, random forest, and SVM-RFE (Sanz et al., 2018) were used to screen for eigengenes.
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Three machine learning algorithms: the least absolute shrinkage and selection operator (LASSO), random forest, and support vector machine-recursive feature elimination (SVM-RFE) were used to screen for signature genes for Parkinson’s disease onset and cuprotosis-related genes (CRG).
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Three machine learning algorithms: the least absolute shrinkage and selection operator (LASSO), random forest, and support vector machine-recursive feature elimination (SVM-RFE) were used to screen for signature genes for Parkinson’s disease onset and cuprotosis-related genes (CRG).
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Three machine learning algorithms: the least absolute shrinkage and selection operator (LASSO), random forest, and support vector machine-recursive feature elimination (SVM-RFE) were used to screen for signature genes for Parkinson’s disease onset and cuprotosis-related genes (CRG).
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label
Principal component analysis
dsl_operations array · 1 item
[0]
pca_fit
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
wide_numeric_matrix
evidence object · 3 fields
score
0.8
band
high
quote
PCA
[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
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high
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limma
[4] object · 10 fields
id
method-5
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machine_learning
specific
support_vector_machine
label
Machine learning
dsl_operations array · 3 items
[0]
train_classifier
[1]
cross_validate
[2]
roc_auc
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data_shapes array · 1 item
[0]
labelled_feature_matrix
evidence object · 3 fields
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0.7
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support vector machine
[5] object · 10 fields
id
method-6
family
correlation_analysis
specific
spearman
label
Correlation analysis
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[0]
spearman_rho
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[0]
paired_numeric_columns
evidence object · 3 fields
score
0.7
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medium
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spearman correlation
[6] object · 10 fields
id
method-7
family
model_calibration
specific
decision_curve
label
Model calibration / clinical utility
dsl_operations array · 2 items
[0]
calibration_bins
[1]
net_benefit
missing_operations array · 0 items
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data_shapes array · 1 item
[0]
predictions_and_outcomes
evidence object · 3 fields
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0.8
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high
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decision curve analysis
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gaps array · 2 items
[0]
method.reader_differs_from_extractor
[1]
method.machine_learning_random_forest
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
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nothing:replicable_now
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method object · 5 fields
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R1
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false
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missing_operations array · 1 item
[0]
machine_learning_random_forest
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: random_forest.
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
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true
accessions array · 5 items
[0]
GSE8397
[1]
GSE7621
[2]
GSE20163
[3]
GSE20186
[4]
GSE42966
resolved_accessions array · 5 items
[0]
GSE8397
[1]
GSE7621
[2]
GSE20163
[3]
GSE20186
[4]
GSE42966
statements array · 1 item
[0]
Publicly available datasets were analyzed in this study. This data can be found here: The datasets analyzed in the current study are available in the GEO (https://www.ncbi.nlm.nih.gov/geo/). All raw data and original images can be found in the jianguoyun (https://www.jianguoyun.com/p/DQEJLh0Q0pH7ChjCutoEIAA).
basis
The paper names GSE8397, GSE7621, GSE20163, GSE20186, GSE42966 in NCBI Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 0 items
assets array · 2 items
[0]
source:pmid:36338988
[1]
data:geo:GSE20163
steps array · 0 items
must_build object · 5 fields
dsl_operations array · 1 item
[0] object · 3 fields
operation
machine_learning_random_forest
priority
null
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readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
[0]
data:geo:GSE20163
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
2026-11-01T18:14:44Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
8893
completion_tokens
2404
cached_tokens
264
stages array · 1 item
[0] object · 4 fields
id
extraction
state
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
[2]
review.human_critique
execution object · 5 fields
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not_run
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null
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gaps array · 1 item
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provenance object · 7 fields
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[0] object · 3 fields
id
pmid:36338988
type
paper
label
pmid:36338988
[1] object · 3 fields
id
source:pmid:36338988
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manuscript
label
PMID 36338988 full text
[2] object · 3 fields
id
data:geo:GSE20163
type
dataset
label
GEO GSE20163
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[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
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[0] object · 3 fields
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pmid:36338988
type
paper
label
pmid:36338988
[1] object · 3 fields
id
source:pmid:36338988
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manuscript
label
PMID 36338988 full text
[2] object · 3 fields
id
data:geo:GSE20163
type
dataset
label
GEO GSE20163
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-36338988
type
extraction
used array · 1 item
[0]
source:pmid:36338988
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE20163
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE20163
agent
agent:corpus-assay-engine
agents array · 2 items
[0] object · 3 fields
id
agent:corpus-assay-engine
type
software
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Corpus assay engine
[1] object · 3 fields
id
agent:minimax-reader
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software
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MiniMax literature reader
source_run_id
reading-sci-2026-11-01
dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
2cb3e42f047d2ecf
snapshot_id
ba34b49490d9bfaf
lineage object · 4 fields
parent_id
pmid:36338988
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sha256:c54ecdac68b2d8697aa5ddb04460dd3a3de77950cdd170b570188ac52317dc73
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null
gaps array · 17 items
[0]
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[1]
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[2]
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[3]
asset:data:geo:GSE20186 not downloaded
[4]
asset:data:geo:GSE42966 licence not read
[5]
asset:data:geo:GSE42966 not downloaded
[6]
asset:data:geo:GSE7621 licence not read
[7]
asset:data:geo:GSE7621 not downloaded
[8]
asset:data:geo:GSE8397 licence not read
[9]
asset:data:geo:GSE8397 not downloaded
[10]
execution.not_run
[11]
method.machine_learning_random_forest
[12]
method.reader_differs_from_extractor
[13]
review.human_critique
[14]
review.independent_reader
[15]
review.machine_critique
[16]
step:run_analysis blocked on method:machine_learning_random_forest
assays array · 1 item
[0] object · 11 fields
role
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machine_learning
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dsl_catalogue
f2132e96ae6c7a4e
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[0]
Three machine learning algorithms: LASSO regression analysis, random forest, and SVM-RFE (Sanz et al., 2018) were used to screen for eigengenes.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36338988", "kind": "science-record", "revision": 5, "content_hash": "sha256:c598bb23b7d93cdda702b06ca1bc975b2a7037fddc49ff65f5729d867bc6d7bf", "created_at": "2026-11-01T18:15:46Z", "updated_at": "2026-11-01T22:50:32Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Machine learning-based characterization of cuprotosis-related biomarkers and immune infiltration in Parkinson's disease.", "doi": "10.3389/fgene.2022.1010361", "pmid": "36338988", "authors": ["Songyun Zhao", "Li Zhang", "Wei Ji", "Yachen Shi", "Guichuan Lai", "Hao Chi", "Weiyi Huang", "Chao Cheng"], "journal": "Frontiers in genetics", "year": 2022, "abstract": "Background: Parkinson's disease (PD) is a neurodegenerative disease commonly seen in the elderly. On the other hand, cuprotosis is a new copper-dependent type of cell death that can be observed in various diseases. Methods: This study aimed to identify potential novel biomarkers of Parkinson's disease by biomarker analysis and to explore immune cell infiltration during the onset of cuprotosis. Gene expression profiles were retrieved from the GEO database for the GSE8397, GSE7621, GSE20163, and GSE20186 datasets. Three machine learning algorithms: the least absolute shrinkage and selection operator (LASSO), random forest, and support vector machine-recursive feature elimination (SVM-RFE) were used to screen for signature genes for Parkinson's disease onset and cuprotosis-related genes (CRG). Immune cell infiltration was estimated by ssGSEA, and cuprotosis-related genes associated with immune cells and immune function were examined using spearman correlation analysis. Nomogram was created to validate the accuracy of these cuprotosis-related genes in predicting PD disease progression. Classification of Parkinson's specimens using consensus clustering methods. Result: Three PD datasets from the Gene Expression Omnibus (GEO) database were combined after eliminating batch effects. By ssGSEA, we identified three cuprotosis-related genes ATP7A, SLC31A1, and DBT associated with immune cells or immune function in PD and more accurate for the diagnosis of Parkinson's disease course. Patients could benefit clinically from a characteristic line graph based on these genes. Consistent clustering analysis identified two subtypes, with the C2 subtype exhibiting higher immune cell infiltration and immune function. Conclusion: In conclusion, our study reveals that several newly identified cuprotosis-related genes intervene in the progression of Parkinson's disease through immune cell infiltration.", "claims": [{"id": "claim-method", "statement": "Three machine learning algorithms: LASSO regression analysis, random forest, and SVM-RFE (Sanz et al., 2018) were used to screen for eigengenes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36338988", "locator": "sections[4] \"Selection of characteristic genes\" paragraph 2", "quote": "Three machine learning algorithms: LASSO regression analysis, random forest, and SVM-RFE (Sanz et al., 2018) were used to screen for eigengenes."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: The datasets analyzed in the current study are available in the GEO (https://www.ncbi.nlm.nih.gov/geo/). All raw data and original images can be found in the jianguoyun (https://www.jianguoyun.com/p/DQEJLh0Q0pH7ChjCutoEIAA).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36338988", "locator": "sections[21] \"Data availability statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: The datasets analyzed in the current study are available in the GEO (https://www.ncbi.nlm.nih.gov/geo/). All raw data and original images can be found in the jianguoyun (https://www.jianguoyun.com/p/DQEJLh0Q0pH7ChjCutoEIAA)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Three machine learning algorithms: the least absolute shrinkage and selection operator (LASSO), random forest, and support vector machine-recursive feature elimination (SVM-RFE) were used to screen for signature genes for Parkinson’s disease onset and cuprotosis-related genes (CRG).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36338988", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Three machine learning algorithms: the least absolute shrinkage and selection operator (LASSO), random forest, and support vector machine-recursive feature elimination (SVM-RFE) were used to screen for signature genes for Parkinson’s disease onset and cuprotosis-related genes (CRG)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Three machine learning algorithms: the least absolute shrinkage and selection operator (LASSO), random forest, and support vector machine-recursive feature elimination (SVM-RFE) were used to screen for signature genes for Parkinson’s disease onset and cuprotosis-related genes (CRG).", "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:36338988"], "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:GSE20163"], "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:machine_learning_random_forest", "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:GSE20163"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:machine_learning_random_forest"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36338988", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2022.1010361", "sha256": "sha256:026fde772616c9957c551fe91ce8f48a03059993b5e4bdbd4369e4b8924cc038", "bytes": 31492, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2022.1010361", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9629507", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE20163", "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=GSE20163", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE20163", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: The datasets analyzed in the current study are available in the GEO (https://www.ncbi.nlm.nih.gov/geo/). All raw data and original images can be found in the jianguoyun (https://www.jianguoyun.com/p/DQEJLh0Q0pH7ChjCutoEIAA).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. This data can be found here: The datasets analyzed in the current study are available in the GEO (https://www.ncbi.nlm.nih.gov/geo/). All raw data and original images can be found in the jianguoyun (https://www.jianguoyun.com/p/DQEJLh0Q0pH7ChjCutoEIAA).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM505996", "GSM505997", "GSM505998", "GSM505999", "GSM506000", "GSM506001", "GSM506002", "GSM506003", "GSM506004", "GSM506005", "GSM506006", "GSM506007", "GSM506008", "GSM506009", "GSM506010", "GSM506011", "GSM506012"], "sample_count": 17, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Systematic meta-analysis and replication of genome-wide expression studies of Parkinson's disease: 2", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE20186", "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=GSE20186", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE20186", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: The datasets analyzed in the current study are available in the GEO (https://www.ncbi.nlm.nih.gov/geo/). All raw data and original images can be found in the jianguoyun (https://www.jianguoyun.com/p/DQEJLh0Q0pH7ChjCutoEIAA).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. This data can be found here: The datasets analyzed in the current study are available in the GEO (https://www.ncbi.nlm.nih.gov/geo/). All raw data and original images can be found in the jianguoyun (https://www.jianguoyun.com/p/DQEJLh0Q0pH7ChjCutoEIAA).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM505716", "GSM505717", "GSM505718", "GSM505719", "GSM505720", "GSM505721", "GSM505722", "GSM505723", "GSM505724", "GSM505725", "GSM505726", "GSM505727", "GSM505728", "GSM505729", "GSM505730", "GSM505731", "GSM505732", "GSM505733", "GSM505734", "GSM505735", "GSM505736", "GSM505737", "GSM505738", "GSM505739", "GSM505740", "GSM505741", "GSM505742", "GSM505743", "GSM505744", "GSM505745", "GSM505746", "GSM505747", "GSM505748", "GSM505996", "GSM505997", "GSM505998", "GSM505999", "GSM506000", "GSM506001", "GSM506002", "GSM506003", "GSM506004", "GSM506005", "GSM506006", "GSM506007", "GSM506008", "GSM506009", "GSM506010", "GSM506011", "GSM506012", "GSM506013", "GSM506014", "GSM506015", "GSM506016", "GSM506017", "GSM506018", "GSM506019", "GSM506020", "GSM506021", "GSM506022", "GSM506023", "GSM509107", "GSM509108", "GSM509109", "GSM509110", "GSM509111", "GSM509112", "GSM509113", "GSM509114"], "sample_count": 69, "group_sizes": null, "group_sizes_basis": null, "platform": "96;6947", "taxon": "Homo sapiens", "title": "Systematic meta-analysis and replication of genome-wide expression studies of Parkinson's disease", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE42966", "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=GSE42966", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE42966", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: The datasets analyzed in the current study are available in the GEO (https://www.ncbi.nlm.nih.gov/geo/). All raw data and original images can be found in the jianguoyun (https://www.jianguoyun.com/p/DQEJLh0Q0pH7ChjCutoEIAA).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. This data can be found here: The datasets analyzed in the current study are available in the GEO (https://www.ncbi.nlm.nih.gov/geo/). All raw data and original images can be found in the jianguoyun (https://www.jianguoyun.com/p/DQEJLh0Q0pH7ChjCutoEIAA).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1054070", "GSM1054071", "GSM1054072", "GSM1054073", "GSM1054074", "GSM1054075", "GSM1054076", "GSM1054077", "GSM1054078", "GSM1054079", "GSM1054080", "GSM1054081", "GSM1054082", "GSM1054083", "GSM1054084"], "sample_count": 15, "group_sizes": null, "group_sizes_basis": null, "platform": "4133", "taxon": "Homo sapiens", "title": "Transcriptional and interactome network analyses of Substantia Nigra in progressive stages of Parkinson’s disease", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE7621", "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=GSE7621", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE7621", "version": null, "note": "Publicly available datasets were analyzed in this study. 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