Mechanistic Clues Provided by Concurrent Changes in the Expression of Genes Encoding the M1 Muscarinic Receptor, β-Catenin Signaling Proteins, and Downstream Targets in Adenocarcinomas of the Colon.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35370785", "kind": "science-record", "revision": 3, "content_hash": "sha256:d43cd5c64f39d6c54040879aca2fddf0ce5b466a4c649dca7d665d0cd0e1e4f7", "created_at": "2026-11-01T18:14:11Z", "updated_at": "2026-11-01T21:27:34Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Mechanistic Clues Provided by Concurrent Changes in the Expression of Genes Encoding the M1 Muscarinic Receptor, β-Catenin Signaling Proteins, and Downstream Targets in Adenocarcinomas of the Colon.", "doi": "10.3389/fphys.2022.857563", "pmid": "35370785", "authors": ["Madeline Alizadeh", "Alyssa Schledwitz", "Kunrong Cheng", "Jean-Pierre Raufman"], "journal": "Frontiers in physiology", "year": 2022, "abstract": "Muscarinic receptors (MRs) in the G protein-coupled receptor superfamily are recipients and mediators of parasympathetic neural transmission within the central and enteric nervous systems. MR subtypes, M1R-M5R, encoded by CHRM1-CHRM5, expressed widely throughout the gastrointestinal (GI) tract, modulate a range of critical, highly regulated activities in healthy tissue, including secretion, motility, and cellular renewal. CHRM3/M3R overexpression in colon cancer is associated with increased cell proliferation, metastasis, and a worse outcome, but little is known about the role of the other four muscarinic receptor subtypes. To address this gap in knowledge, we queried the NCI Genomic Data Commons for publicly available TCGA-COAD samples collected from colon tissue. RNA-seq data were collected and processed for all available primary adenocarcinomas paired with adjacent normal colon. In this unbiased analysis, 78 paired samples were assessed using correlation coefficients and univariate linear regressions; gene ontologies were performed on a subset of correlated genes. We detected a consistent pattern of CHRM1 downregulation across colorectal adenocarcinomas. CHRM1 expression levels were positively associated with those for APC and SMAD4, and negatively associated with CTNNB1, the gene for β-catenin, and with coordinate changes in the expression of β-catenin target genes. These findings implicating CHRM1/M1R as an important deterrent of colon cancer development and progression warrant further exploration.", "claims": [{"id": "claim-method", "statement": "Univariate mixed linear models comparing the final processed counts of various genes and CHRM1, controlling for participant ID, were generated using the nlme package in R (Pinheiro et al., 2021).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35370785", "locator": "sections[6] \"Differential Expression and Model Analysis\" paragraph 2", "quote": "Univariate mixed linear models comparing the final processed counts of various genes and CHRM1, controlling for participant ID, were generated using the nlme package in R (Pinheiro et al., 2021)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analyzed for this study can be found in the Genomic Data Commons, at https://portal.gdc.cancer.gov/, under the TCGA-COAD project.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35370785", "locator": "sections[15] \"Data Availability Statement\" paragraph 2", "quote": "The datasets analyzed for this study can be found in the Genomic Data Commons, at https://portal.gdc.cancer.gov/, under the TCGA-COAD project."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In this unbiased analysis, 78 paired samples were assessed using correlation coefficients and univariate linear regressions; gene ontologies were performed on a subset of correlated genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35370785", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In this unbiased analysis, 78 paired samples were assessed using correlation coefficients and univariate linear regressions; gene ontologies were performed on a subset of correlated genes."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "In this unbiased analysis, 78 paired samples were assessed using correlation coefficients and univariate linear regressions; gene ontologies were performed on a subset of correlated genes.", "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:35370785"], "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:35370785", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fphys.2022.857563", "sha256": "sha256:e44c4f002b2562454721ffda806ed172a1a25455e608c35adf36bebe87390be1", "bytes": 47684, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fphys.2022.857563", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8966224", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": null, "specific": null, "label": "univariate mixed linear models controlling for participant ID", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Univariate mixed linear models comparing the final processed counts of various genes and CHRM1, controlling for participant ID, were generated using the nlme package in R (Pinheiro et al., 2021)."}}], "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": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R4", "expressible": false, "required_operations": [], "missing_operations": [], "basis": "The reader quoted the method the paper names (univariate mixed linear models controlling for participant ID), but the corpus's method extractor could not map it onto a DSL operation, so the method is published but not expressible."}, "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": ["The datasets analyzed for this study can be found in the Genomic Data Commons, at https://portal.gdc.cancer.gov/, under the TCGA-COAD project."], "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:35370785"], "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": "2026-11-01T17:40:35Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 14262, "completion_tokens": 1452, "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:35370785", "type": "paper", "label": "pmid:35370785"}, {"id": "source:pmid:35370785", "type": "manuscript", "label": "PMID 35370785 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35370785", "type": "paper", "label": "pmid:35370785"}, {"id": "source:pmid:35370785", "type": "manuscript", "label": "PMID 35370785 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35370785", "type": "extraction", "used": ["source:pmid:35370785"], "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:35370785", "parent_hash": "sha256:3502cfbe857cf724f25ac3623f752a09f62eadecd76a81e366bc1f70338e79e2", "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": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["GA-COAD samples collected from colon tissue. RNA-seq data were collected and processed for all av"], "order_basis": "paper_text_order:930", "id": "assay:1"}]}