HIDE: hierarchical cell-type deconvolution.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40662776", "kind": "science-record", "revision": 2, "content_hash": "sha256:bd866437d2de7e8dfcd5717e96df8a958c2004cb07d711fa8cf34b7f7a2890a6", "created_at": "2026-11-01T20:30:45Z", "updated_at": "2026-11-01T21:35:27Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "HIDE: hierarchical cell-type deconvolution.", "doi": "10.1093/bioinformatics/btaf179", "pmid": "40662776", "authors": ["Dennis Völkl", "Malte Mensching-Buhr", "Thomas Sterr", "Sarah Bolz", "Andreas Schäfer", "Nicole Seifert", "Jana Tauschke", "Austin Rayford", "Oddbjørn Straume", "Helena U Zacharias", "Sushma Nagaraja Grellscheid", "Tim Beissbarth", "Michael Altenbuchinger", "Franziska Görtler"], "journal": "Bioinformatics (Oxford, England)", "year": 2025, "abstract": "MOTIVATION: Cell-type deconvolution is a computational approach to infer cellular distributions from bulk transcriptomics data. Several methods have been proposed, each with its own advantages and disadvantages. Reference based approaches make use of archetypic transcriptomic profiles representing individual cell types. Those reference profiles are ideally chosen such that the observed bulks can be reconstructed as a linear combination thereof. This strategy, however, ignores the fact that cellular populations arise through the process of cellular differentiation, which entails the gradual emergence of cell groups with diverse morphological and functional characteristics.\nRESULTS: Here, we propose Hierarchical cell-type Deconvolution (HIDE), a cell-type deconvolution approach which incorporates a cell hierarchy for improved performance and interpretability. This is achieved by a hierarchical procedure that preserves estimates of major cell populations while inferring their respective subpopulations. We show in simulation studies that this procedure produces more reliable and more consistent results than other state-of-the-art approaches. Finally, we provide an example application of HIDE to explore breast cancer specimens from TCGA.\nAVAILABILITY AND IMPLEMENTATION: A python implementation of HIDE is available at zenodo (doi: 10.5281/zenodo.14724906).", "claims": [{"id": "claim-method", "statement": "The predicted cell type proportions were analyzed for their association with patient survival via Cox regression, using the CoxPHFitter function from lifelines 0.30.0 (https://lifelines.readthedocs.io/en/latest/) with robust errors to account for possible violations of the model assumptions (Lin and Wei 1989).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40662776", "locator": "sections[12] \"3.4 Breast cancer subtype analysis using bulk transcriptomics data from TCGA\" paragraph 2", "quote": "The predicted cell type proportions were analyzed for their association with patient survival via Cox regression, using the CoxPHFitter function from lifelines 0.30.0 (https://lifelines.readthedocs.io/en/latest/) with robust errors to account for possible violations of the model assumptions (Lin and Wei 1989)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Supplementary data are available at Bioinformatics online", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40662776", "locator": "sections[20] \"Supplementary data\" paragraph 2", "quote": "Supplementary data are available at Bioinformatics online"}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "", "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:40662776"], "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:40662776", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1093/bioinformatics/btaf179", "sha256": "sha256:66028cee2daad0411fceab913809f30dc1fbfb17e17ad4750655d3704c20f684", "bytes": 49464, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1093/bioinformatics/btaf179", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12261400", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The predicted cell type proportions were analyzed for their association with patient survival via Cox regression, using the CoxPHFitter function from lifelines 0.30.0 (https://lifelines.readthedocs.io/en/latest/) with robust errors to account for possible violations of the model assumptions (Lin and Wei 1989)."}}], "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": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "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": ["Supplementary data are available at Bioinformatics online"], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:40662776"], "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": "2026-11-01T19:57:11Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 13147, "completion_tokens": 1421, "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:40662776", "type": "paper", "label": "pmid:40662776"}, {"id": "source:pmid:40662776", "type": "manuscript", "label": "PMID 40662776 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40662776", "type": "paper", "label": "pmid:40662776"}, {"id": "source:pmid:40662776", "type": "manuscript", "label": "PMID 40662776 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40662776", "type": "extraction", "used": ["source:pmid:40662776"], "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:40662776", "parent_hash": "sha256:2f1ab8f24cc02cdef8eb8c20bd3a3a9c4efecad42e851a39949b77dab4369777", "fork_of": null, "generation": 1}, "gaps": ["execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent"], "assays": [{"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The predicted cell type proportions were analyzed for their association with patient survival via Cox regression, using the CoxPHFitter function from lifelines 0.30.0 (https://lifelines.readthedocs.io/en/latest/) with robust errors to account for possible violations of the model assumptions (Lin and Wei 1989)."], "order_basis": "analysis_only", "id": "assay:1"}]}