Towards future directions in data-integrative supervised prediction of human aging-related genes.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36699345", "kind": "science-record", "revision": 3, "content_hash": "sha256:0baa3ad4b8d82c6b36bc7bcc74ec14d8e633b58fa47db5f195a599cb472dca5d", "created_at": "2026-11-01T19:01:15Z", "updated_at": "2026-11-01T22:08:37Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Towards future directions in data-integrative supervised prediction of human aging-related genes.", "doi": "10.1093/bioadv/vbac081", "pmid": "36699345", "authors": ["Qi Li", "Khalique Newaz", "Tijana Milenković"], "journal": "Bioinformatics advances", "year": 2022, "abstract": "Motivation: Identification of human genes involved in the aging process is critical due to the incidence of many diseases with age. A state-of-the-art approach for this purpose infers a weighted dynamic aging-specific subnetwork by mapping gene expression (GE) levels at different ages onto the protein-protein interaction network (PPIN). Then, it analyzes this subnetwork in a supervised manner by training a predictive model to learn how network topologies of known aging- versus non-aging-related genes change across ages. Finally, it uses the trained model to predict novel aging-related gene candidates. However, the best current subnetwork resulting from this approach still yields suboptimal prediction accuracy. This could be because it was inferred using outdated GE and PPIN data. Here, we evaluate whether analyzing a weighted dynamic aging-specific subnetwork inferred from newer GE and PPIN data improves prediction accuracy upon analyzing the best current subnetwork inferred from outdated data.\nResults: Unexpectedly, we find that not to be the case. To understand this, we perform aging-related pathway and Gene Ontology term enrichment analyses. We find that the suboptimal prediction accuracy, regardless of which GE or PPIN data is used, may be caused by the current knowledge about which genes are aging-related being incomplete, or by the current methods for inferring or analyzing an aging-specific subnetwork being unable to capture all of the aging-related knowledge. These findings can potentially guide future directions towards improving supervised prediction of aging-related genes via -omics data integration.\nAvailability and implementation: All data and code are available at zenodo, DOI: 10.5281/zenodo.6995045.\nSupplementary information: Supplementary data are available at Bioinformatics Advances online.", "claims": [{"id": "claim-method", "statement": "We train and test each predictive model via 5-fold cross-validation in terms of prediction accuracy (AUPR, precision, recall and F-score averaged over the five folds).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36699345", "locator": "sections[11] \"3 Results\" paragraph 2", "quote": "We train and test each predictive model via 5-fold cross-validation in terms of prediction accuracy (AUPR, precision, recall and F-score averaged over the five folds)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data and code are available at zenodo, DOI: 10.5281/zenodo.6995045.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36699345", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "All data and code are available at zenodo, DOI: 10.5281/zenodo.6995045."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using newer GTEx gene-expression data or BioGRID protein–protein interaction data did not improve aging-related gene prediction accuracy over using older Berchtold and HPRD data.", "kind": "quantitative", "target": {"value": 52.0, "unit": "per cent", "tolerance": null, "source": "However, our subnetworks are imperfect regardless of what data they are inferred from: the highest AUPR, precision, recall and F-score over all subnetworks are 50, 67, 45 and 52%, respectively."}, "evidence": [{"asset": "source:pmid:36699345", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Unexpectedly, we find that not to be the case."}, {"asset": "source:pmid:36699345", "locator": "sections[3] \"1.2 Our study and contribution\" paragraph 7", "quote": "However, our subnetworks are imperfect regardless of what data they are inferred from: the highest AUPR, precision, recall and F-score over all subnetworks are 50, 67, 45 and 52%, respectively."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Using newer GTEx gene-expression data or BioGRID protein–protein interaction data did not improve aging-related gene prediction accuracy over using older Berchtold and HPRD data.", "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:36699345"], "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": "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": {}, "inputs": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36699345", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1093/bioadv/vbac081", "sha256": "sha256:cc050c797eb64ba1d0350cb23fa0541b9995f800e9f1d5cb5bfc3c906fbbcad7", "bytes": 56201, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1093/bioadv/vbac081", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9710570", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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-2", "family": null, "specific": null, "label": "5-fold cross-validation", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "We train and test each predictive model via 5-fold cross-validation in terms of prediction accuracy (AUPR, precision, recall and F-score averaged over the five folds)."}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "build_graph", "expected_value": 52.0, "unit": "per cent", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}], "gaps": ["method.reader_named_unmapped"]}, "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": true, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ppi_network."}, "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 data and code are available at zenodo, DOI: 10.5281/zenodo.6995045."], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "assets": ["source:pmid:36699345"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "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": "2026-11-01T18:24:46Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 14588, "completion_tokens": 2407, "cached_tokens": 264}}, "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:36699345", "type": "paper", "label": "pmid:36699345"}, {"id": "source:pmid:36699345", "type": "manuscript", "label": "PMID 36699345 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36699345", "type": "paper", "label": "pmid:36699345"}, {"id": "source:pmid:36699345", "type": "manuscript", "label": "PMID 36699345 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36699345", "type": "extraction", "used": ["source:pmid:36699345"], "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:36699345", "parent_hash": "sha256:1298e78de87b44f520f80c2e51b341c92961d8e175e1d0f978db0db3cc8a0aad", "fork_of": null, "generation": 2}, "gaps": ["execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent"], "assays": [{"role": "analysis", "definition_id": "network_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["protein-protein interaction"], "order_basis": "analysis_only", "id": "assay:1"}]}