Multi-Cell Line Analysis of Lysosomal Proteomes Reveals Unique Features and Novel Lysosomal Proteins.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36791992", "kind": "science-record", "revision": 2, "content_hash": "sha256:d9965240ddd405164d364f8d7ba1aa3ec43dbc850ac799c64797ef036edc0651", "created_at": "2026-11-01T19:01:22Z", "updated_at": "2026-11-01T21:30:08Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Multi-Cell Line Analysis of Lysosomal Proteomes Reveals Unique Features and Novel Lysosomal Proteins.", "doi": "10.1016/j.mcpro.2023.100509", "pmid": "36791992", "authors": ["Fatema Akter", "Sara Bonini", "Srigayatri Ponnaiyan", "Bianca Kögler-Mohrbacher", "Florian Bleibaum", "Markus Damme", "Bernhard Y Renard", "Dominic Winter"], "journal": "Molecular & cellular proteomics : MCP", "year": 2023, "abstract": "Lysosomes, the main degradative organelles of mammalian cells, play a key role in the regulation of metabolism. It is becoming more and more apparent that they are highly active, diverse, and involved in a large variety of processes. The essential role of lysosomes is exemplified by the detrimental consequences of their malfunction, which can result in lysosomal storage disorders, neurodegenerative diseases, and cancer. Using lysosome enrichment and mass spectrometry, we investigated the lysosomal proteomes of HEK293, HeLa, HuH-7, SH-SY5Y, MEF, and NIH3T3 cells. We provide evidence on a large scale for cell type-specific differences of lysosomes, showing that levels of distinct lysosomal proteins are highly variable within one cell type, while expression of others is highly conserved across several cell lines. Using differentially stable isotope-labeled cells and bimodal distribution analysis, we furthermore identify a high confidence population of lysosomal proteins for each cell line. Multi-cell line correlation of these data reveals potential novel lysosomal proteins, and we confirm lysosomal localization for six candidates. All data are available via ProteomeXchange with identifier PXD020600.", "claims": [{"id": "claim-method", "statement": "For each cell line, we estimated the mixture of two univariate normal distributions and assigned a posterior probability of lysosomal localization to each protein using an expectation-maximization algorithm (40).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36791992", "locator": "sections[27] \"Bimodal Distribution Analysis Revealed Specifically Enriched Proteins\" paragraph 3", "quote": "For each cell line, we estimated the mixture of two univariate normal distributions and assigned a posterior probability of lysosomal localization to each protein using an expectation-maximization algorithm (40)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (92) partner repository and are publicly available (http://proteomecentral.proteomexchange.org/) with the dataset identifier PXD020600. MS/MS spectrum identifications from MaxQuant searches were deposited at MS-Viewer (93) and are publicly available (https://msviewer.ucsf.edu/) with the search keys c0vxdeqfnr (combined human datasets from HEK293, HeLa, HuH-7, and SH-SY5Y cells) and qwtwxcxfbm (combined mouse datasets from MEF and NIH3T3 cells).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36791992", "locator": "sections[31] \"Data Availability\" paragraph 2", "quote": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (92) partner repository and are publicly available (http://proteomecentral.proteomexchange.org/) with the dataset identifier PXD020600. MS/MS spectrum identifications from MaxQuant searches were deposited at MS-Viewer (93) and are publicly available (https://msviewer.ucsf.edu/) with the search keys c0vxdeqfnr (combined human datasets from HEK293, HeLa, HuH-7, and SH-SY5Y cells) and qwtwxcxfbm (combined mouse datasets from MEF and NIH3T3 cells)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using differentially stable isotope-labeled cells and bimodal distribution analysis, the study identified a high-confidence population of lysosomal proteins for each cell line and confirmed lysosomal localization for six candidates.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36791992", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Using differentially stable isotope-labeled cells and bimodal distribution analysis, we furthermore identify a high confidence population of lysosomal proteins for each cell line."}, {"asset": "source:pmid:36791992", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Multi–cell line correlation of these data reveals potential novel lysosomal proteins, and we confirm lysosomal localization for six candidates."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using differentially stable isotope-labeled cells and bimodal distribution analysis, the study identified a high-confidence population of lysosomal proteins for each cell line and confirmed lysosomal localization for six candidates.", "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:36791992"], "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:PXD020600"], "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": ["data:geo:PXD020600"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36791992", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.mcpro.2023.100509", "sha256": "sha256:90026d78eb865d8660a72ef150fd73eec68be071978579ecff6aef09337bce42", "bytes": 90137, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.mcpro.2023.100509", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10025164", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:PXD020600", "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=PXD020600", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD020600", "version": null, "note": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (92) partner repository and are publicly available (http://proteomecentral.proteomexchange.org/) with the dataset identifier PXD020600. MS/MS spectrum identifications from MaxQuant searches were deposited at MS-Viewer (93) and are publicly available (https://msviewer.ucsf.edu/) with the search keys c0vxdeqfnr (combined human datasets from HEK293, HeLa, HuH-7, and SH-SY5Y cells) and qwtwxcxfbm (combined mouse datasets from MEF and NIH3T3 cells).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (92) partner repository and are publicly available (http://proteomecentral.proteomexchange.org/) with the dataset identifier PXD020600. MS/MS spectrum identifications from MaxQuant searches were deposited at MS-Viewer (93) and are publicly available (https://msviewer.ucsf.edu/) with the search keys c0vxdeqfnr (combined human datasets from HEK293, HeLa, HuH-7, and SH-SY5Y cells) and qwtwxcxfbm (combined mouse datasets from MEF and NIH3T3 cells).", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "Multi cell line comparison of lysosome enriched fractions reveals cell type specific features and novel lysosomal proteins", "resolution_checked_at": "2026-11-01T18:46:41Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:PXD020600 not downloaded", "asset:data:geo:PXD020600 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Pearson correlation"}}, {"id": "method-2", "family": "clustering", "specific": "hierarchical", "label": "Clustering", "dsl_operations": ["hierarchical_cluster"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["feature_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "hierarchical clustering"}}, {"id": "method-3", "family": null, "specific": null, "label": "Bimodal distribution analysis using an expectation-maximization algorithm", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "For each cell line, we estimated the mixture of two univariate normal distributions and assigned a posterior probability of lysosomal localization to each protein using an expectation-maximization algorithm (40)."}}], "targets": [], "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": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["pearson_r"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: pearson."}, "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": ["PXD020600"], "resolved_accessions": ["PXD020600"], "statements": ["The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (92) partner repository and are publicly available (http://proteomecentral.proteomexchange.org/) with the dataset identifier PXD020600. MS/MS spectrum identifications from MaxQuant searches were deposited at MS-Viewer (93) and are publicly available (https://msviewer.ucsf.edu/) with the search keys c0vxdeqfnr (combined human datasets from HEK293, HeLa, HuH-7, and SH-SY5Y cells) and qwtwxcxfbm (combined mouse datasets from MEF and NIH3T3 cells)."], "basis": "The paper names PXD020600 in ProteomeXchange Consortium via the PRIDE partner repository and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["pearson_r"], "assets": ["source:pmid:36791992", "data:geo:PXD020600"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:PXD020600"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:27:33Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 22072, "completion_tokens": 2547, "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:36791992", "type": "paper", "label": "pmid:36791992"}, {"id": "source:pmid:36791992", "type": "manuscript", "label": "PMID 36791992 full text"}, {"id": "data:geo:PXD020600", "type": "dataset", "label": "GEO PXD020600"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36791992", "type": "paper", "label": "pmid:36791992"}, {"id": "source:pmid:36791992", "type": "manuscript", "label": "PMID 36791992 full text"}, {"id": "data:geo:PXD020600", "type": "dataset", "label": "GEO PXD020600"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36791992", "type": "extraction", "used": ["source:pmid:36791992"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-PXD020600", "type": "accession_resolution", "used": ["data:geo:PXD020600"], "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:36791992", "parent_hash": "sha256:8438e66da9b36573e1bf95454b6db8312d8816d42236ebfe0bcb37e8d774ad3a", "fork_of": null, "generation": 1}, "gaps": ["asset:data:geo:PXD020600 licence not read", "asset:data:geo:PXD020600 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "mass_spectrometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["s, and cancer. Using lysosome enrichment and mass spectrometry, we investigated the lysosomal proteomes of", "plete SILAC labeling. Sample Preparation for Mass Spectrometry For each sample, 100 μg of protein was preci", "Design and Statistical Rationale Samples for mass spectrometric analysis were generated for each cell line i", "ed fractions of the individual cell lines by mass spectrometry–based proteomics (Fig. 1A and supplemental T"], "order_basis": "paper_text_order:511", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": [", we investigated the lysosomal proteomes of HEK293, HeLa, HuH-7, SH-SY5Y, MEF, and NIH3T3 cells", "estigated the lysosomal proteomes of HEK293, HeLa, HuH-7, SH-SY5Y, MEF, and NIH3T3 cells. We p", "lysosomal proteomes of HEK293, HeLa, HuH-7, SH-SY5Y, MEF, and NIH3T3 cells. We provide evidence", "es of HEK293, HeLa, HuH-7, SH-SY5Y, MEF, and NIH3T3 cells. We provide evidence on a large scale"], "order_basis": "paper_text_order:573", "id": "assay:2"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["cell line), 5235 were identified in the two mouse cell lines with 75% and 90% unique identific", "al compartment in PANTHER and/or UniProt for mouse or human, irrespective of the fact if they f"], "order_basis": "paper_text_order:4337", "id": "assay:3"}, {"role": "analysis", "definition_id": "correlation_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pearson_r"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Pearson correlation"], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}