A transcriptional signature detects homologous recombination deficiency in pancreatic cancer at the individual level.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34786207", "kind": "science-record", "revision": 5, "content_hash": "sha256:27ae485124597ac984702c7c06c789662e1c1a7dc24368146db9cc7021f4d7d8", "created_at": "2026-11-01T17:36:29Z", "updated_at": "2026-11-01T22:47:53Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A transcriptional signature detects homologous recombination deficiency in pancreatic cancer at the individual level.", "doi": "10.1016/j.omtn.2021.10.014", "pmid": "34786207", "authors": ["Shuping Zhuang", "Tingting Chen", "Yawei Li", "Yuquan Wang", "Liqiang Ai", "Yiding Geng", "Min Zou", "Kaidong Liu", "Huanhuan Xu", "Linzhu Wang", "Zhangxiang Zhao", "Zhiqiang Chang", "Yunyan Gu"], "journal": "Molecular therapy. Nucleic acids", "year": 2021, "abstract": "Pancreatic cancer (PC) with homologous recombination deficiency (HRD) has been reported to benefit from poly ADP-ribose polymerase (PARP) inhibitors. However, accurate identification of HRD status for PC patients from the transcriptional level is still a great challenge. Here, based on a relative expression ordering (REO)-based algorithm, we developed an HRD signature including 24 gene pairs (24-GPS) using PC transcriptional profiles from The Cancer Genome Atlas (TCGA). HRD samples classified by 24-GPS showed worse overall survival (p = 4.4E-3 for TCGA; p = 1.2E-3 for International Cancer Genome Consortium-Australia cohort; p = 6.4E-2 for GSE17891; p = 7.5E-2 for GSE57495) and higher HRD scores than non-HRD samples (p = 1.4E-4). HRD samples showed highly unstable genomic characteristics and also displayed HRD-related alterations at the epigenomic and proteomic levels. Moreover, HRD cell lines identified by 24-GPS tended to be sensitive to PARP inhibitors (p = 6.6E-2 for olaparib; p = 2.6E-3 for niraparib). Compared with the non-HRD group, the HRD group presented lower immune scores and CD4/CD8 T cell infiltration proportion. Interestingly, PC tumor cells with co-inhibition of PARP-related genes and ATR showed reduced survival ability. In conclusion, 24-GPS can robustly identify PC patients with HRD status at the individualized level.", "claims": [{"id": "claim-method", "statement": "Multiple HRD-related features were compared among clusters using Wilcoxon rank-sum test. OS was estimated by Kaplan-Meier curves and tested by log-rank test with p value less than 0.05. Finally, we implemented the LASSO model to further optimize the 1,000 gene pairs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34786207", "locator": "sections[14] \"Unsupervised clustering\" paragraph 2", "quote": "Multiple HRD-related features were compared among clusters using Wilcoxon rank-sum test."}, {"asset": "source:pmid:34786207", "locator": "sections[24] \"Survival analysis\" paragraph 2", "quote": "OS was estimated by Kaplan-Meier curves and tested by log-rank test with p value less than 0.05."}, {"asset": "source:pmid:34786207", "locator": "sections[15] \"Discovering a REO-based HRD signature\" paragraph 2", "quote": "Finally, we implemented the LASSO model to further optimize the 1,000 gene pairs."}], "state": "complete"}, {"id": "claim-data-access", "statement": "For samples documented in ICGC-AU, GSE17891 and GSE57495 datasets were used to validate the signature.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34786207", "locator": "sections[11] \"Data sources\" paragraph 2", "quote": "For samples documented in ICGC-AU, GSE17891 and GSE57495 datasets were used to validate the signature."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The REO-based 24-GPS classified 147 TCGA pancreatic cancer samples into 37 HRD and 110 non-HRD cases, with an AUC of 0.98.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34786207", "locator": "sections[3] \"Discovering HRD signature for PC\" paragraph 4", "quote": "As a result, 147 PC samples were classified into 37 HRD (25.2%) and 110 non-HRD (74.8%) with an area under curve (AUC) of 0.98 (Figure 1E)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The REO-based 24-GPS classified 147 TCGA pancreatic cancer samples into 37 HRD and 110 non-HRD cases, with an AUC of 0.98.", "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:34786207"], "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:GSE17891"], "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:GSE17891"], "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:34786207", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.omtn.2021.10.014", "sha256": "sha256:8dddefe6230feb2f9c5b46a0402200bae9b384d0b9443bcf0114291a464dc842", "bytes": 52037, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.omtn.2021.10.014", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8571416", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE17891", "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=GSE17891", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE17891", "version": null, "note": "For samples documented in ICGC-AU, GSE17891 and GSE57495 datasets were used to validate the signature.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "For samples documented in ICGC-AU, GSE17891 and GSE57495 datasets were used to validate the signature.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM446731", "GSM446732", "GSM446733", "GSM446734", "GSM446735", "GSM446736", "GSM446737", "GSM446738", "GSM446739", "GSM446740", "GSM446741", "GSM446742", "GSM446743", "GSM446744", "GSM446745", "GSM446746", "GSM446747", "GSM446748", "GSM446749", "GSM446750", "GSM446751", "GSM446752", "GSM446753", "GSM446754", "GSM446755", "GSM446756", "GSM446757", "GSM446763", "GSM446764", "GSM446765", "GSM446766", "GSM446767", "GSM446768", "GSM446769", "GSM446770", "GSM446771", "GSM446772", "GSM446773", "GSM446774", "GSM446775", "GSM446776", "GSM446777", "GSM446778", "GSM446779", "GSM446780", "GSM446781", "GSM446782", "GSM451598", "GSM451599", "GSM451600", "GSM451601", "GSM451602", "GSM451603", "GSM451604", "GSM451605", "GSM451606", "GSM451607", "GSM451608", "GSM451609", "GSM451610", "GSM451611", "GSM451612"], "sample_count": 62, "group_sizes": null, "group_sizes_basis": null, "platform": "8321;570", "taxon": "Mus musculus; 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