Dual role of Cathepsin S in cutaneous melanoma: insights from mendelian randomization and bioinformatics analysis.

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P value < 0.05 indicates the presence of heterogeneity or horizontal pleiotropy", "rows": [["exposure/outcome", "Horizontal pleiotropy", "Heterogeneity"], ["MR-Egger regression", "MR-PRESSO", "Methods", "Cochran’s Q", "P value"], ["Egger intercept", "SE", "P value", "Global test P value", "Outliers", "MR Egger", "10", "0.02*"], ["CTSS/CM", "-0.005", "0.055", "0.93", "0.085", "NULL", "IVW", "11", "0.03*"]], "row_count": 4, "column_count": 9, "numeric_cells": 8, "header_rows": 3, "locator": "section[16]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:39833734:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:3c154e48a5d165efe044a216a6f6aefdb018b66b8153623ab446712732c4339b", "bytes": 1522, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[1]#Tab2", "version": null, "note": "Gene Ontology (GO) analysis of key proteins for PPI screening. Abbreviations: BP — biological process; CC — cellular component; MF — molecular function. FDR — false discovery rate", "structure": {"pmcid": "PMC11744831", "section_index": 17, "section_title": "CTSS may play a dual role in CM through multiple bio-informatics analyses", "row_count": 15, "column_count": 6}, "table": {"label": "Table 2", "caption": "Gene Ontology (GO) analysis of key proteins for PPI screening. Abbreviations: BP — biological process; CC — cellular component; MF — molecular function. FDR — false discovery rate", "rows": [["Go term", "Ontology", "Description", "count in network", "Strength", "FDR"], ["GO:0097048", "BP", "Dendritic cell apoptotic process", "2 of 2", "3.25", "0.0021"], ["GO:2,000,669", "BP", "Negative regulation of dendritic cell apoptotic process", "2 of 9", "2.6", "0.007"], ["GO:0097284", "BP", "Hepatocyte apoptotic process", "2 of 13", "2.44", "0.0108"], ["GO:0001836", "BP", "Release of cytochrome c from mitochondria", "3 of 21", "2.41", "0.00096"], ["GO:0002903", "BP", "Negative regulation of B cell apoptotic process", "2 of 15", "2.38", "0.0121"], ["GO:0004920", "MF", "Interleukin-10 receptor activity", "2 of 2", "3.25", "0.0084"], ["GO:0051434", "MF", "BH3 domain binding", "2 of 6", "2.78", "0.0195"], ["GO:0004896", "MF", "Cytokine receptor activity", "3 of 96", "1.75", "0.0306"], ["GO:0004197", "MF", "Cysteine-type endopeptidase activity", "3 of 124", "1.64", "0.0341"], ["GO:0036021", "CC", "Endolysosome lumen", "3 of 5", "3.03", "1.48E-05"], ["GO:0043202", "CC", "Lysosomal lumen", "4 of 97", "1.87", "0.00014"], ["GO:0005775", "CC", "Vacuolar lumen", "5 of 175", "1.71", "2.72E-05"], ["GO:1,904,813", "CC", "Ficolin-1-rich granule lumen", "3 of 124", "1.64", "0.0106"], ["GO:0005741", "CC", "Mitochondrial outer membrane", "3 of 209", "1.41", "0.0278"]], "row_count": 15, "column_count": 6, "numeric_cells": 58, "header_rows": 1, "locator": "section[17]/table-wrap[1]#Tab2"}}, {"id": "asset:table:pmid:39833734:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:301255d2c43a329aa100759e781f697486bd622d2c613e15fa9cfad2390fb05f", "bytes": 622, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[2]#Tab3", "version": null, "note": "Kyoto Encyclopedia of genes and genomes (KEGG) analysis of key proteins for PPI screening", "structure": {"pmcid": "PMC11744831", "section_index": 17, "section_title": "CTSS may play a dual role in CM through multiple bio-informatics analyses", "row_count": 6, "column_count": 5}, "table": {"label": "Table 3", "caption": "Kyoto Encyclopedia of genes and genomes (KEGG) analysis of key proteins for PPI screening", "rows": [["Pathway", "Description", "count in network", "Strength", "FDR"], ["hsa04215", "Apoptosis", "3 of 30", "2.25", "4.70E-05"], ["hsa04612", "Antigen processing and presentation", "4 of 64", "2.05", "4.70E-06"], ["hsa01524", "Platinum drug resistance", "3 of 70", "1.89", "0.00038"], ["hsa04115", "p53 signaling pathway", "3 of 72", "1.87", "0.00038"], ["hsa05145", "Toxoplasmosis", "4 of 103", "1.84", "2.21E-05"]], "row_count": 6, "column_count": 5, "numeric_cells": 21, "header_rows": 1, "locator": "section[17]/table-wrap[2]#Tab3"}}], "gaps": ["asset:source:pmid:39833734 not verified"]}, "analysis": {"state": "absent", "methods": [], "targets": [], "gaps": ["method", "targets"]}, "capability": {"state": "absent", "requirements": [], "gaps": ["capability"]}, "readiness": {"state": "partial", "tier": null, "blocking_axis": null, "blocked_on": null, "axes": {}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:39833734", "asset:table:pmid:39833734:1", "asset:table:pmid:39833734:2", "asset:table:pmid:39833734:3"], "steps": ["read_published_estimate"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": ["xml"], "capabilities": [], "data_gaps": ["source:pmid:39833734"]}, "gaps": ["corpus_record_absent"]}, "review": {"state": "partial", "machine_critique": {"status": "blocked", "providers": [{"provider": "minimax", "model": "MiniMax-M3.1-Flash", "prompt_version": "full-text-reading-v1", "prompt_hash": "ca5650ce02f244c33658271b44492990764ac0affd950570466c31dc46cea7d4", "source_hash": "fe28f54b37d02b346a2558c419fcf9ce0816f602a02a7d68155a28bc2c894eba", "raw_response_sha256": "sha256:bbecc51809a96bceb09b072655b59cd88abbb86ac8194e7096ad7a063bfa870c", "raw_response_chars": 4972}, {"provider": "minimax_alt", "model": "MiniMax-M3", "prompt_version": "full-text-reading-v1", "prompt_hash": "751d98fe576dcab56a48e9c4f07ca329c6aaa74d2988ed87835836b94ad872f0", "source_hash": "fe28f54b37d02b346a2558c419fcf9ce0816f602a02a7d68155a28bc2c894eba", "raw_response_sha256": "sha256:6b14b9398f8d16b7a429867ffded3afcc1723131fc731be56688308fd0920404", "raw_response_chars": 71659}], "target_providers": [{"provider": "minimax", "model": "MiniMax-M3.1-Flash", "prompt_version": "replication-target-v2", "prompt_hash": "044aaa8839e254580887e1ecdf32bae8455eb9593241bf7c3e131db72db362c4", "source_hash": "fe28f54b37d02b346a2558c419fcf9ce0816f602a02a7d68155a28bc2c894eba", "raw_response": "{\"parent_value\":1.316,\"unit\":\"odds ratio (OR)\",\"evidence\":\"Using the Inverse variances weighted (IVW) method, we calculated the odds ratio (OR) of 1.316 (95% CI ranging 1.194–1.450, P = 3.02 × 10− 8) for CTSS impact on CM.\",\"target_result\":\"The odds ratio for CTSS impact on cutaneous melanoma using the inverse-variance weighted method was 1.316.\",\"number_stated\":true}", "reading": {"parent_value": 1.316, "unit": "odds ratio (OR)", "evidence": "Using the Inverse variances weighted (IVW) method, we calculated the odds ratio (OR) of 1.316 (95% CI ranging 1.194–1.450, P = 3.02 × 10− 8) for CTSS impact on CM.", "target_result": "The odds ratio for CTSS impact on cutaneous melanoma using the inverse-variance weighted method was 1.316.", "number_stated": true, "source_locator": "chars 8538-8701 of source sha256 fe28f54b37d02b346a2558c419fcf9ce0816f602a02a7d68155a28bc2c894eba"}, "recorded_at": "2026-10-31T15:21:52.224422+00:00"}, {"provider": "minimax_alt", "model": "MiniMax-M3", "prompt_version": "replication-target-v2", "prompt_hash": "0b11ac158144af9e6b7d0392c306687b604d9da7ecd297e09bc2dad2ca27f137", "source_hash": "fe28f54b37d02b346a2558c419fcf9ce0816f602a02a7d68155a28bc2c894eba", "raw_response": "<think>We need produce JSON only extracting headline numerical result for registered target main finding. Need reason what headline number is. Source paper says MR IVW OR 1.316 for CTSS impact CM. Need report headline number value paper states registered target main finding, unit printed. Evidence exact contiguous quote contains number, whole clause if attribution via wording. Could be 1.316 unit odds ratio (OR), quote sentence \"Using the Inverse variances weighted (IVW) method, we calculated the odds ratio (OR) of 1.316 (95% CI ranging 1.194–1.450, P = 3.02 × 10− 8) for CTSS impact on CM.\" Need determine whether headline number is OR 1.316 (IVW main analytical tool). Could alternatively headline 232 DEGs but main finding CTSS causal OR 1.316. Most likely 1.316, unit \"odds ratio\" or \"OR\". Need unit exactly unit paper prints. It prints odds ratio (OR). So unit \"odds ratio (OR)\" perhaps. Target_result textual perhaps \"The paper reports an odds ratio (OR) of 1.316 for CTSS impact on CM using the inverse variance weighted method.\" Evidence exact contiguous quote, can include full sentence. Need ensure phrase not altered. Actual source \"Using the Inverse variances weighted (IVW) method, we calculated the odds ratio (OR) of 1.316 (95% CI ranging 1.194–1.450, P = 3.02 × 10− 8) for CTSS impact on CM.\" We can quote as is including spacing. JSON escapes? Unicode fine.\n\nWe must follow user instructions single numerical result, headline number only: \"Report the headline number only: the value the paper itself states for the registered target, not a value you calculated, converted, averaged or reconstructed.\" We output parent_value 1.316, unit odds ratio (OR), evidence quote full clause for checking. They explicitly evidence full clause. target_result can minimal \"1.316 (odds ratio)\" perhaps avoid other numerical results. number_stated true.\n\nNeed think whether unit dimensionless (\"odds ratio\") they expect maybe \"OR\". \"unit must be the unit the paper prints\". It says \"odds ratio (OR)\" so \"odds ratio (OR)\" likely. Could choose \"odds ratio\" no unit? Usually extraction tasks parent_value and unit could be unit \"OR\". They want printed unit. Could be \"odds ratio (OR)\" safe.\n\nNeed not include confidence interval as number in parent_value. Evidence includes numbers but unavoidable. \"headline number only\" means no extras. target_result could \"The paper states an odds ratio (OR) of 1.316 for CTSS impact on CM using the inverse variance weighted method.\" Exact quote in evidence. It uses \"Inverse variances weighted (IVW)\" which is main method. We can directly say \"The paper reports an odds ratio (OR) of 1.316 for CTSS impact on CM using the Inverse variances weighted (IVW) method.\" No unsupported interpretation.\n\nConsider if \"headline numerical result paper states for main finding\" might be 232 DEGs since abstract says 232 differentially expressed genes, main finding only CTSS causal. But target is headline numerical result main finding. The numerical effect is 1.316, highlighted from main method. Paper abstract no OR. Could they want 232? Let's reason likely benchmark style. Registered target generic \"the headline numerical result the paper states for its main finding\" extraction answer should main numerical result. Main causal effect OR 1.316. 232 DEGs is pipeline not main effect. They might identify result as \"odds ratio of 1.316\" because main finding CTSS deleterious and OR. Good.\n\nNeed ensure no \"confidence interval\" unit. We can set unit \"odds ratio (OR)\". target_result maybe \"The reported CTSS–CM causal association had an odds ratio (OR) of 1.316 using the Inverse variances weighted (IVW) method.\" More direct paper wording with quote. Evidence exact sentence. No need include final period? exact contiguous quote can include it. We quote sentence including end. In source text period follows CM. Include.\n\nWill output JSON proper.</think>\n\n{\n  \"parent_value\": 1.316,\n  \"unit\": \"odds ratio (OR)\",\n  \"evidence\": \"Using the Inverse variances weighted (IVW) method, we calculated the odds ratio (OR) of 1.316 (95% CI ranging 1.194–1.450, P = 3.02 × 10− 8) for CTSS impact on CM.\",\n  \"target_result\": \"The paper reports an odds ratio (OR) of 1.316 for CTSS impact on CM using the Inverse variances weighted (IVW) method.\",\n  \"number_stated\": true\n}", "reading": {"parent_value": 1.316, "unit": "odds ratio (OR)", "evidence": "Using the Inverse variances weighted (IVW) method, we calculated the odds ratio (OR) of 1.316 (95% CI ranging 1.194–1.450, P = 3.02 × 10− 8) for CTSS impact on CM.", "target_result": "The paper reports an odds ratio (OR) of 1.316 for CTSS impact on CM using the Inverse variances weighted (IVW) method.", "number_stated": true, "source_locator": "chars 8538-8701 of source sha256 fe28f54b37d02b346a2558c419fcf9ce0816f602a02a7d68155a28bc2c894eba"}, "recorded_at": "2026-10-31T15:22:07.079208+00:00"}], "agreement": false, "disagreements": {"target_result": {"minimax": "CTSS in sun-exposed skin showed a positive causal association with cutaneous melanoma, with an odds ratio of 1.316 (95% CI 1.194–1.450, P = 3.02 × 10−8) using inverse variance weighting.", "minimax_alt": "Positive causal relationship between CTSS in sun-exposed skin and cutaneous melanoma, with an odds ratio (OR) of 1.316 (95% CI ranging 1.194–1.450, P = 3.02 × 10− 8) using the Inverse variances weighted (IVW) method.", "decisive": false}, "analysis_methods": {"minimax": ["Two-sample Mendelian randomization", "Inverse variance weighting", "MR-Egger regression", "Weighted median", "Simple mode", "Weighted mode", "Cochran's Q test", "Leave-One-Out analysis", "MR-PRESSO test"], "minimax_alt": ["Differential expression analysis using log2 fold-change and false discovery rate thresholds", "Two-sample Mendelian randomization (TSMR)", "Inverse variance weighted (IVW) with a random-effects model", "MR-Egger", "Weighted median", "Simple mode", "Weighted mode", "Cochran’s Q test", "Leave-One-Out method", "MR-PRESSO test", "MR-Egger regression"], "decisive": false}, "statistical_method": {"minimax": "Inverse variance weighting (IVW)", "minimax_alt": "Inverse variances weighted (IVW) method", "decisive": true}}, "agreement_basis": {"policy": "decisive_fields", "decisive_fields": ["work_type", "number_stated", "parent_value", "unit"]}, "blinded": true}, "human_critique": {"status": "not_run", "reviewer": null, "signed_at": null, "conflict_checked": false, "commentary": null}, "stages": [{"key": "target_materials", "status": "pending", "reason": null, "evidence": null}, {"key": "independent_readings", "status": "blocked", "reason": "The independent readings are incomplete or disagree; the source evidence must resolve the difference.", "evidence": {"provider_errors": []}}, {"key": "source_resolution", "status": "pending", "reason": null, "evidence": null}, {"key": "protocol_reconstruction", "status": "pending", "reason": null, "evidence": null}, {"key": "control_execution", "status": "pending", "reason": null, "evidence": null}, {"key": "control_comparison", "status": "pending", "reason": null, "evidence": null}, {"key": "publication", "status": "pending", "reason": null, "evidence": null}], "gaps": ["review.human_critique", "review.machine_critique.blocked"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "package:38f8f485adfaec87e540a0ad33e8091189b9b67af95873010d264b31e80231da", "type": "sep_package", "label": "SEP v1 package for pmid:39833734"}], "activities": [{"id": "activity:conversion:pmid:39833734", "type": "conversion", "used": ["package:38f8f485adfaec87e540a0ad33e8091189b9b67af95873010d264b31e80231da"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:minimax", "type": "model", "label": "minimax"}, {"id": "agent:minimax_alt", "type": "model", "label": "minimax_alt"}, {"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}], "source_run_id": "run-20261023T122449232913", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:39833734", "parent_hash": "sha256:4305465ab313bd41bb7e97f8fe7330e7783c55bc81c8ddc61891150da0b1014f", "fork_of": null, "generation": 2}, "gaps": ["abstract", "asset:source:pmid:39833734 not verified", "authors", "capability", "corpus_record_absent", "execution.not_run", "method", "review.human_critique", "review.machine_critique.blocked", "step:obtain_source_data blocked on data:not_downloaded", "step:run_analysis blocked on no owned computational capability is bound to this experiment", "step:run_analysis input 'materials:the source data behind the published result in pmid:39833734' does not resolve to a declared asset", "targets"]}