Correlation of genetic alterations by whole-exome sequencing with clinical outcomes of glioblastoma patients from the Lebanese population.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33237934", "kind": "science-record", "revision": 7, "content_hash": "sha256:937f6ccf2f31fade33da9b97472593ce78a4bacb9b87e206be664a438ff583d8", "created_at": "2026-11-01T15:41:17Z", "updated_at": "2026-11-01T22:02:36Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Correlation of genetic alterations by whole-exome sequencing with clinical outcomes of glioblastoma patients from the Lebanese population.", "doi": "10.1371/journal.pone.0242793", "pmid": "33237934", "authors": ["Fadi S Saadeh", "Rami Z Morsi", "Abdallah El-Kurdi", "Georges Nemer", "Rami Mahfouz", "Maya Charafeddine", "Jessica Khoury", "Marwan W Najjar", "Pierre Khoueiry", "Hazem I Assi"], "journal": "PloS one", "year": 2020, "abstract": "INTRODUCTION: Glioblastoma (GBM) is an aggressive brain tumor associated with high degree of resistance to treatment. Given its heterogeneity, it is important to understand the molecular landscape of this tumor for the development of more effective therapies. Because of the different genetic profiles of patients with GBM, we sought to identify genetic variants in Lebanese patients with GBM (LEB-GBM) and compare our findings to those in the Cancer Genome Atlas (TCGA).\nMETHODS: We performed whole exome sequencing (WES) to identify somatic variants in a cohort of 60 patient-derived GBM samples. We focused our analysis on 50 commonly mutated GBM candidate genes and compared mutation signatures between our population and publicly available GBM data from TCGA. We also cross-tabulated biological covariates to assess for associations with overall survival, time to recurrence and follow-up duration.\nRESULTS: We included 60 patient-derived GBM samples from 37 males and 23 females, with age ranging from 3 to 80 years (mean and median age at diagnosis were 51 and 56, respectively). Recurrent tumor formation was present in 94.8% of patients (n = 55/58). After filtering, we identified 360 somatic variants from 60 GBM patient samples. After filtering, we identified 360 somatic variants from 60 GBM patient samples. Most frequently mutated genes in our samples included ATRX, PCDHX11, PTEN, TP53, NF1, EGFR, PIK3CA, and SCN9A. Mutations in NLRP5 were associated with decreased overall survival among the Lebanese GBM cohort (p = 0.002). Mutations in NLRP5 were associated with decreased overall survival among the Lebanese GBM cohort (p = 0.002). EGFR and NF1 mutations were associated with the frontal lobe and temporal lobe in our LEB-GBM cohort, respectively.\nCONCLUSIONS: Our WES analysis confirmed the similarity in mutation signature of the LEB-GBM population with TCGA cohorts. It showed that 1 out of the 50 commonly GBM candidate gene mutations is associated with decreased overall survival among the Lebanese cohort. This study also highlights the need for studies with larger sample sizes to inform clinicians for better prognostication and management of Lebanese patients with GBM.", "claims": [{"id": "claim-data-access", "statement": "All relevant data are within the paper and its Supporting information files. The data contain potentially identifying information and thus cannot be shared publicly. There are legal and ethical restrictions on sharing our de-identified data imposed by the Institutional Review Board (IRB). Data access requests can be sent to the IRB. Email: irb@aub.edu.lb Telephone: 00961 -1-350000 or 1 374374, ext: 5445 Fax: +961 1 738025 PO BOX: 11-0236 F15 Riad El Solh, Beirut 1107 2020 Lebanon.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33237934", "locator": "sections[15] \"Data Availability\" paragraph 2", "quote": "All relevant data are within the paper and its Supporting information files. The data contain potentially identifying information and thus cannot be shared publicly. There are legal and ethical restrictions on sharing our de-identified data imposed by the Institutional Review Board (IRB). Data access requests can be sent to the IRB. Email: irb@aub.edu.lb Telephone: 00961 -1-350000 or 1 374374, ext: 5445 Fax: +961 1 738025 PO BOX: 11-0236 F15 Riad El Solh, Beirut 1107 2020 Lebanon."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "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:33237934"], "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": "blocked", "blocked_on": "data:accession_absent", "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": [], "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:student_t", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:student_t", "step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33237934", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1371/journal.pone.0242793", "sha256": "sha256:d09c7e1b6c7d99a35894f6fe32617a891cac8de85024dab9144e1fb946990bfb", "bytes": 46492, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1371/journal.pone.0242793", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7688136", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "asset:table:pmid:33237934:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:654cec4acec429cbd3bc63878a83df45d09a9f68cde5e489b6cb08761fed5130", "bytes": 1172, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#pone.0242793.t001", "version": null, "note": "Comparison of common GBM gene mutations between the LEB-GBM cohort and the TCGA cohort.", "structure": {"pmcid": "PMC7688136", "section_index": 10, "section_title": "Distribution of frequently mutated genes across LEB-GBM patients", "row_count": 11, "column_count": 9}, "table": {"label": "Table 1", "caption": "Comparison of common GBM gene mutations between the LEB-GBM cohort and the TCGA cohort.", "rows": [["Gene", "Mutation", "Type of Mutation", "# Affected Samples (n = 60)", "% Affected Samples (n = 60)a", "95% CI (LEB-GBM Cohort)a", "# TCGA (n = 391)", "% TCGA (n = 391)b", "95% CI (TCGA Cohort)b"], ["IDH1", "R132H", "Missense", "6", "10.0", "2.4–17.6", "23", "5.9", "3.6–8.2"], ["EGFR", "A289V", "Missense", "1", "1.7", "-1.6–4.9", "15", "3.8", "1.9–5.7"], ["EGFR", "G598V", "Missense", "3", "5.0", "-0.5–10.5", "13", "3.3", "1.5–5.1"], ["TP53", "R175H", "Missense", "2", "3.3", "-1.2–7.9", "8", "2.0", "0.6–3.4"], ["TP53", "R248Q", "Missense", "2", "3.3", "1.1–5.8", "7", "1.8", "0.5–3.1"], ["EGFR", "R222C", "Missense", "0", "0.0", "0.0–0.0", "6", "1.5", "0.3–2.8"], ["TP53", "R248W", "Missense", "1", "1.7", "-1.6–4.9", "5", "1.3", "0.2–2.4"], ["TP53", "R282W", "Missense", "0", "0.0", "0.0–0.0", "5", "1.3", "0.2–2.4"], ["EGFR", "A289D", "Missense", "0", "0.0", "0.0–0.0", "5", "1.3", "0.2–2.4"], ["BRAF", "V600E", "Missense", "2", "3.3", "-1.2–7.9", "5", "1.3", "0.2–2.4"]], "row_count": 11, "column_count": 9, "numeric_cells": 80, "header_rows": 1, "locator": "section[10]/table-wrap[1]#pone.0242793.t001"}}], "gaps": []}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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-2", "family": "sequence_alignment", "specific": "read_mapping", "label": "Sequence alignment / homology", "dsl_operations": ["sequence_align", "alignment_identity"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["sequence_records"], "evidence": {"score": 0.8, "band": "high", "quote": "BWA"}}, {"id": "method-3", "family": "contingency_analysis", "specific": "chi_square", "label": "Categorical (contingency table) analysis", "dsl_operations": ["chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 0.8, "band": "high", "quote": "Chi-square"}}], "targets": [], "gaps": ["method.student_t"]}, "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": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R1", "expressible": false, "required_operations": [], "missing_operations": ["student_t"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: student_t_test."}, "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": "R4", "reachable": false, "accessions": [], "resolved_accessions": [], "statements": ["All relevant data are within the paper and its Supporting information files. The data contain potentially identifying information and thus cannot be shared publicly. There are legal and ethical restrictions on sharing our de-identified data imposed by the Institutional Review Board (IRB). Data access requests can be sent to the IRB. Email: irb@aub.edu.lb Telephone: 00961 -1-350000 or 1 374374, ext: 5445 Fax: +961 1 738025 PO BOX: 11-0236 F15 Riad El Solh, Beirut 1107 2020 Lebanon."], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:33237934", "asset:table:pmid:33237934:1"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "student_t", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:None"]}, "gaps": ["data:accession_absent"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T19:16:59Z", "independence": "single_reader"}, "evidence_check": {"method": "absent", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 42304, "completion_tokens": 1220, "cached_tokens": 776}}, "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:33237934", "type": "paper", "label": "pmid:33237934"}, {"id": "source:pmid:33237934", "type": "manuscript", "label": "PMID 33237934 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33237934", "type": "paper", "label": "pmid:33237934"}, {"id": "source:pmid:33237934", "type": "manuscript", "label": "PMID 33237934 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33237934", "type": "extraction", "used": ["source:pmid:33237934"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-None", "type": "accession_resolution", "used": ["data:geo:None"], "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:33237934", "parent_hash": "sha256:b1d19ee1212a123c83bc87f417481389f97afbb8245483991a21436b56b24a14", "fork_of": null, "generation": 6}, "gaps": ["execution.not_run", "method.student_t", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent", "step:run_analysis blocked on method:student_t"], "assays": [{"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Student t-test"], "order_basis": "analysis_only", "id": "assay:1"}]}