← All .science files
pmid:34981661
Potential biomarkers and therapeutic targets of idiopathic pulmonary arterial hypertension.
Wenjun He · Xi Su · Lingdan Chen · Chunli Liu · Wenju Lu · Tao Wang · Jian Wang
Physiological reports · 2022 doi:10.14814/phy2.15101
Paper
complete
Experiment
complete
Data
partial
Analysis
complete
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
paper object · 10 fields
authors array · 7 items
claims array · 3 items
[0] object · 6 fields
evidence array · 1 item
[0] object · 3 fields
[1] object · 6 fields
gaps array · 0 items
experiment object · 8 fields
steps array · 3 items
[0] object · 13 fields
parameters object · 0 fields
inputs array · 1 item
outputs array · 1 item
instruments array · 0 items
reagents array · 0 items
[1] object · 13 fields
parameters object · 0 fields
inputs array · 1 item
outputs array · 1 item
instruments array · 0 items
reagents array · 0 items
[2] object · 13 fields
parameters object · 1 field
inputs array · 1 item
outputs array · 1 item
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 · 0 items
data object · 3 fields
assets array · 3 items
[0] object · 15 fields
structure object · 4 fields
[1] object · 15 fields
structure object · 15 fields
sample_accessions array · 140 items
[2] object · 15 fields
structure object · 15 fields
sample_accessions array · 53 items
gaps array · 4 items
analysis object · 4 fields
methods array · 3 items
[0] object · 10 fields
dsl_operations array · 3 items
missing_operations array · 0 items
parameters object · 1 field
data_shapes array · 1 item
[1] object · 10 fields
dsl_operations array · 3 items
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[2] object · 10 fields
dsl_operations array · 1 item
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
targets array · 0 items
gaps array · 0 items
capability object · 3 fields
requirements array · 1 item
[0] object · 6 fields
assay_families array · 9 items
gaps array · 0 items
readiness object · 8 fields
axes object · 3 fields
method object · 5 fields
required_operations array · 3 items
missing_operations array · 0 items
capability object · 4 fields
data object · 6 fields
accessions array · 2 items
resolved_accessions array · 2 items
statements array · 1 item
can_run object · 3 fields
dsl_operations array · 3 items
assets array · 2 items
steps array · 1 item
must_build object · 5 fields
dsl_operations array · 0 items
converters array · 0 items
readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
gaps array · 0 items
review object · 5 fields
machine_critique object · 5 fields
reader object · 5 fields
evidence_check object · 2 fields
usage object · 3 fields
stages array · 1 item
[0] object · 4 fields
gaps array · 3 items
provenance object · 7 fields
entities array · 3 items
activities array · 3 items
[0] object · 4 fields
used array · 3 items
[0] object · 3 fields
[1] object · 3 fields
[2] object · 3 fields
[1] object · 4 fields
agents array · 2 items
lineage object · 4 fields
gaps array · 8 items
assays array · 1 item
[0] object · 11 fields
required_operations array · 3 items
source_hashes object · 1 field
evidence array · 1 item
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34981661", "kind": "science-record", "revision": 5, "content_hash": "sha256:dd6b51875e310db241c0dd2f6913ce9f850aad7cd8a6e38dbc053d7de53ea0c4", "created_at": "2026-11-01T17:36:41Z", "updated_at": "2026-11-01T22:48:10Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Potential biomarkers and therapeutic targets of idiopathic pulmonary arterial hypertension.", "doi": "10.14814/phy2.15101", "pmid": "34981661", "authors": ["Wenjun He", "Xi Su", "Lingdan Chen", "Chunli Liu", "Wenju Lu", "Tao Wang", "Jian Wang"], "journal": "Physiological reports", "year": 2022, "abstract": "BACKGROUND: Peripheral blood mononuclear cells (PBMCs) play an important role in the pathogenesis of pulmonary arterial hypertension (PAH). However, the specific roles of PBMCs in the development and progression of idiopathic PAH (IPAH) have not been fully understood.\nMETHODS: Here, differentially expressed genes (DEGs) of PBMCs or lung tissues between IPAH patients and healthy controls were identified via bioinformatics analysis of Gene Expression Omnibus (GEO) datasets GSE33463 and GSE48149, respectively. Subsequently, extensive target prediction and network analysis were performed to assess protein-protein interaction (PPI) networks, Gene Ontology (GO) terms, and pathway enrichment for DEGs. Co-expressed DEGs between PBMCs and lung tissues coupled with corresponding predicted miRNAs involved in PAH were also assessed. We identified 251 DEGs in PBMCs and 151 DEGs in lung tissue samples from IPAH. PDK4, RBPMS2, and PDE5A expression were altered in both PBMCs and lung tissues from IPAH patients compared to healthy control.\nRESULTS: CXCL8, JUN, TLR8, IL1B, and TLR7 could be implicated as the hub genes in PBMCs, whereas ENO1, STAT1, CXCL10, GPI, and IRF1 in lung tissues. Finally, co-expressed DEGs of PDK4, RBPMS2, and PDE5A coupled with corresponding predicted miRNAs, especially miR-103a-3p, miR-185-5p, and miR-515-5p, are significantly associated with IPAH.\nCONCLUSION: Our findings collectively suggest that the expression levels of PDK4, RBPMS2, and PDE5A in PBMCs are associated with the expression of these genes in lung tissues. Thus, these molecules may serve as potential circulating biomarkers and/or possible therapeutic targets for IPAH.", "claims": [{"id": "claim-method", "statement": "R packages of “Illumina” and “limma” (http://www.bioconductor.org/packages/release/bioc/html/limma.html), provided by a Bioconductor project, were applied to assess GSE33463 and GSE48149 RAW datasets.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34981661", "locator": "sections[4] \"Identification of the differentially expressed genes\" paragraph 2", "quote": "R packages of “Illumina” and “limma” (http://www.bioconductor.org/packages/release/bioc/html/limma.html), provided by a Bioconductor project, were applied to assess GSE33463 and GSE48149 RAW datasets."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. Discovery cohort and duplication cohort (GSE33463 and GSE48149) were downloaded from GEO (http://www.ncbi.nlm.nih.gov/geo/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34981661", "locator": "sections[22] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. Discovery cohort and duplication cohort (GSE33463 and GSE48149) were downloaded from GEO (http://www.ncbi.nlm.nih.gov/geo/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The bioinformatics analysis identified 251 DEGs in PBMCs and 151 DEGs in lung tissue samples from IPAH patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34981661", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "We identified 251 DEGs in PBMCs and 151 DEGs in lung tissue samples from IPAH."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The bioinformatics analysis identified 251 DEGs in PBMCs and 151 DEGs in lung tissue samples from IPAH patients.", "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:34981661"], "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:GSE33463"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {"fdr_threshold": "with Benjamin–Hochberg false discovery rate adjustment"}, "inputs": ["data:geo:GSE33463"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34981661", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.14814/phy2.15101", "sha256": "sha256:8b240759851a2e6d07e65edd60a89f1ace75d290caa21d3565a122fe3c6054f5", "bytes": 38007, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.14814/phy2.15101", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8724678", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE33463", "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=GSE33463", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE33463", "version": null, "note": "Publicly available datasets were analyzed in this study. Discovery cohort and duplication cohort (GSE33463 and GSE48149) were downloaded from GEO (http://www.ncbi.nlm.nih.gov/geo/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. Discovery cohort and duplication cohort (GSE33463 and GSE48149) were downloaded from GEO (http://www.ncbi.nlm.nih.gov/geo/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM827665", "GSM827666", "GSM827667", "GSM827668", "GSM827669", "GSM827670", "GSM827671", "GSM827672", "GSM827673", "GSM827674", "GSM827675", "GSM827676", "GSM827677", "GSM827678", "GSM827679", "GSM827680", "GSM827681", "GSM827682", "GSM827683", "GSM827684", "GSM827685", "GSM827686", "GSM827687", "GSM827688", "GSM827689", "GSM827690", "GSM827691", "GSM827692", "GSM827693", "GSM827694", "GSM827695", "GSM827696", "GSM827697", "GSM827698", "GSM827699", "GSM827700", "GSM827701", "GSM827702", "GSM827703", "GSM827704", "GSM827705", "GSM827706", "GSM827707", "GSM827708", "GSM827709", "GSM827710", "GSM827711", "GSM827712", "GSM827713", "GSM827714", "GSM827715", "GSM827716", "GSM827717", "GSM827718", "GSM827719", "GSM827720", "GSM827721", "GSM827722", "GSM827723", "GSM827724", "GSM827725", "GSM827726", "GSM827727", "GSM827728", "GSM827729", "GSM827730", "GSM827731", "GSM827732", "GSM827733", "GSM827734", "GSM827735", "GSM827736", "GSM827737", "GSM827738", "GSM827739", "GSM827740", "GSM827741", "GSM827742", "GSM827743", "GSM827744", "GSM827745", "GSM827746", "GSM827747", "GSM827748", "GSM827749", "GSM827750", "GSM827751", "GSM827752", "GSM827753", "GSM827754", "GSM827755", "GSM827756", "GSM827757", "GSM827758", "GSM827759", "GSM827760", "GSM827761", "GSM827762", "GSM827763", "GSM827764", "GSM827765", "GSM827766", "GSM827767", "GSM827768", "GSM827769", "GSM827770", "GSM827771", "GSM827772", "GSM827773", "GSM827774", "GSM827775", "GSM827776", "GSM827777", "GSM827778", "GSM827779", "GSM827780", "GSM827781", "GSM827782", "GSM827783", "GSM827784", "GSM827785", "GSM827786", "GSM827787", "GSM827788", "GSM827789", "GSM827790", "GSM827791", "GSM827792", "GSM827793", "GSM827794", "GSM827795", "GSM827796", "GSM827797", "GSM827798", "GSM827799", "GSM827800", "GSM827801", "GSM827802", "GSM827803", "GSM827804"], "sample_count": 140, "group_sizes": null, "group_sizes_basis": null, "platform": "6947", "taxon": "Homo sapiens", "title": "Erythroid-Specific Transcriptional Changes in PBMCs from Pulmonary Hypertension Patients", "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:GSE48149", "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=GSE48149", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE48149", "version": null, "note": "Publicly available datasets were analyzed in this study. Discovery cohort and duplication cohort (GSE33463 and GSE48149) were downloaded from GEO (http://www.ncbi.nlm.nih.gov/geo/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. Discovery cohort and duplication cohort (GSE33463 and GSE48149) were downloaded from GEO (http://www.ncbi.nlm.nih.gov/geo/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1169960", "GSM1169961", "GSM1169962", "GSM1169963", "GSM1169964", "GSM1169965", "GSM1169966", "GSM1169967", "GSM1169968", "GSM1169969", "GSM1169970", "GSM1169971", "GSM1169972", "GSM1169973", "GSM1169974", "GSM1169975", "GSM1169976", "GSM1169977", "GSM1169978", "GSM1169979", "GSM1169980", "GSM1169981", "GSM1169982", "GSM1169983", "GSM1169984", "GSM1169985", "GSM1169986", "GSM1169987", "GSM1169988", "GSM1169989", "GSM1169990", "GSM1169991", "GSM1169992", "GSM1169993", "GSM1169994", "GSM1169995", "GSM1169996", "GSM1169997", "GSM1169998", "GSM1169999", "GSM1170000", "GSM1170001", "GSM1170002", "GSM1170003", "GSM1170004", "GSM1170005", "GSM1170006", "GSM1170007", "GSM1170008", "GSM1170009", "GSM1170010", "GSM1170011", "GSM1170012"], "sample_count": 53, "group_sizes": null, "group_sizes_basis": null, "platform": "16221", "taxon": "Homo sapiens", "title": "Lung tissues in systemic sclerosis have gene expression patterns unique to pulmonary fibrosis and pulmonary hypertension", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE33463 not downloaded", "asset:data:geo:GSE33463 licence not read", "asset:data:geo:GSE48149 not downloaded", "asset:data:geo:GSE48149 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {"fdr_threshold": "with Benjamin–Hochberg false discovery rate adjustment"}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "R packages of “Illumina” and “limma” (http://www.bioconductor.org/packages/release/bioc/html/limma.html), provided by a Bioconductor project, were applied to assess GSE33463 and GSE48149 RAW datasets."}}, {"id": "method-2", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}, {"id": "method-3", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "pathway enrichment"}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "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": ["GSE33463", "GSE48149"], "resolved_accessions": ["GSE33463", "GSE48149"], "statements": ["Publicly available datasets were analyzed in this study. Discovery cohort and duplication cohort (GSE33463 and GSE48149) were downloaded from GEO (http://www.ncbi.nlm.nih.gov/geo/)."], "basis": "The paper names GSE33463, GSE48149 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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:34981661", "data:geo:GSE33463"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE33463"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:13:55Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 12683, "completion_tokens": 1225, "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:34981661", "type": "paper", "label": "pmid:34981661"}, {"id": "source:pmid:34981661", "type": "manuscript", "label": "PMID 34981661 full text"}, {"id": "data:geo:GSE33463", "type": "dataset", "label": "GEO GSE33463"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34981661", "type": "paper", "label": "pmid:34981661"}, {"id": "source:pmid:34981661", "type": "manuscript", "label": "PMID 34981661 full text"}, {"id": "data:geo:GSE33463", "type": "dataset", "label": "GEO GSE33463"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34981661", "type": "extraction", "used": ["source:pmid:34981661"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE33463", "type": "accession_resolution", "used": ["data:geo:GSE33463"], "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:34981661", "parent_hash": "sha256:5d3de535e93340f0ec99e0166f427d33658a74e678379df5dc7fca743195d89c", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE33463 licence not read", "asset:data:geo:GSE33463 not downloaded", "asset:data:geo:GSE48149 licence not read", "asset:data:geo:GSE48149 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["R packages of “Illumina” and “limma” (http://www.bioconductor.org/packages/release/bioc/html/limma.html), provided by a Bioconductor project, were applied to assess GSE33463 and GSE48149 RAW datasets."], "order_basis": "analysis_only", "id": "assay:1"}]}