Pathway analysis identifies altered mitochondrial metabolism, neurotransmission, structural pathways and complement cascade in retina/RPE/ choroid in chick model of form-deprivation myopia.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:29967729", "kind": "science-record", "revision": 6, "content_hash": "sha256:22fca9a8b308bb0a334d5a8c328fb98588c072fdff7497d35c685852e7025cb7", "created_at": "2026-11-01T15:40:35Z", "updated_at": "2026-11-01T21:21:31Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Pathway analysis identifies altered mitochondrial metabolism, neurotransmission, structural pathways and complement cascade in retina/RPE/ choroid in chick model of form-deprivation myopia.", "doi": "10.7717/peerj.5048", "pmid": "29967729", "authors": ["Loretta Giummarra", "Sheila G Crewther", "Nina Riddell", "Melanie J Murphy", "David P Crewther"], "journal": "PeerJ", "year": 2018, "abstract": "PURPOSE: RNA sequencing analysis has demonstrated bidirectional changes in metabolism, structural and immune pathways during early induction of defocus induced myopia. Thus, the aim of this study was to investigate whether similar gene pathways are also related to the more excessive axial growth, ultrastructural and elemental microanalytic changes seen during the induction and recovery from form-deprivation myopia (FDM) in chicks and predicted by the RIDE model of myopia.\nMETHODS: Archived genomic transcriptome data from the first three days of induction of monocularly occluded form deprived myopia (FDMI) in chicks was obtained from the GEO database (accession # GSE6543) while data from chicks monocularly occluded for 10 days and then given up to 24 h of normal visual recovery (FDMR) were collected. Gene set enrichment analysis (GSEA) software was used to determine enriched pathways during the induction (FDMI) and recovery (FDMR) from FD. Curated gene-sets were obtained from open access sources.\nRESULTS: Clusters of significant changes in mitochondrial energy metabolism, neurotransmission, ion channel transport, G protein coupled receptor signalling, complement cascades and neuron structure and growth were identified during the 10 days of induction of profound myopia and were found to correlate well with change in axial dimensions. Bile acid and bile salt metabolism pathways (cholesterol/lipid metabolism and sodium channel activation) were significantly upregulated during the first 24 h of recovery from 10 days of FDM.\nCONCLUSIONS: The gene pathways altered during induction of FDM are similar to those reported in defocus induced myopia and are established indicators of oxidative stress, osmoregulatory and associated structural changes. These findings are also consistent with the choroidal thinning, axial elongation and hyperosmotic ion distribution patterns across the retina and choroid previously reported in FDM and predicted by RIDE.", "claims": [{"id": "claim-data-access", "statement": "The following information was supplied regarding data availability:The data discussed in this article are available in NCBI’s Gene Expression Omnibus under accession number GSE89325.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29967729", "locator": "sections[32] \"Microarray Data Availability\" paragraph 2", "quote": "The following information was supplied regarding data availability:The data discussed in this article are available in NCBI’s Gene Expression Omnibus under accession number GSE89325."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The paper used Gene Set Enrichment Analysis (GSEA) to compare archived GEO induction data (GSE6543) with newly collected FDMR microarray data, finding pathway changes involving mitochondrial energy metabolism, neurotransmission, ion transport, complement cascades, and bile acid metabolism.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:29967729", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Gene set enrichment analysis (GSEA) software was used to determine enriched pathways during the induction (FDMI) and recovery (FDMR) from FD."}, {"asset": "source:pmid:29967729", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Archived genomic transcriptome data from the first three days of induction of monocularly occluded form deprived myopia (FDMI) in chicks was obtained from the GEO database (accession # GSE6543) while data from chicks monocularly occluded for 10 days and then given up to 24 h of normal visual recovery (FDMR) were collected."}, {"asset": "source:pmid:29967729", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Clusters of significant changes in mitochondrial energy metabolism, neurotransmission, ion channel transport, G protein coupled receptor signalling, complement cascades and neuron structure and growth were identified during the 10 days of induction of profound myopia and were found to correlate well with change in axial dimensions. Bile acid and bile salt metabolism pathways (cholesterol/lipid metabolism and sodium channel activation) were significantly upregulated during the first 24 h of recovery from 10 days of FDM."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The paper used Gene Set Enrichment Analysis (GSEA) to compare archived GEO induction data (GSE6543) with newly collected FDMR microarray data, finding pathway changes involving mitochondrial energy metabolism, neurotransmission, ion transport, complement cascades, and bile acid metabolism.", "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:29967729"], "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. 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Most genes responding to FD are involved in mitochondrial energy metabolism. The NES reflects the degree to which a set of genes is over-represented at either the top or bottom of a ranked list of genes while also taking into account differences in pathway size (i.e. gene-set size) and is the primary statistic for examining enrichment results, and for comparing results across pathways.", "structure": {"pmcid": "PMC6026464", "section_index": 15, "section_title": "Enrichment analysis for short-term FDM induction", "row_count": 14, "column_count": 5}, "table": {"label": "Table 1", "caption": "Pathways enriched between 6 h and 72 h of FD induction.Mean Normalised Enrichment Score (NES) and false discovery rate (FDR) for the biological pathways identified by GSEA in FD induction. Most genes responding to FD are involved in mitochondrial energy metabolism. The NES reflects the degree to which a set of genes is over-represented at either the top or bottom of a ranked list of genes while also taking into account differences in pathway size (i.e. gene-set size) and is the primary statistic for examining enrichment results, and for comparing results across pathways.", "rows": [["Pathway", "Core genes", "Database", "NES", "FDR"], ["Huntingtons disease", "APAF1, ATP5C1, ATP5D, ATP5E, ATP5F1, ATP5H, ATP5O, BDNF, CASP3, CASP8, CLTA, COX4I1, COX5A, COX6A1, COX6C, COX7A2, COX7A2L, COX7C, COX8A, CYCS, DNAH3, DNAI1, DNAL1, DNALI1, GPX1, HDAC2, IFT57, NDUFA1, NDUFA10, NDUFA2, NDUFA4, NDUFA5, NDUFA6, NDUFA7, NDUFA8, NDUFB1, NDUFB10, NDUFB3, NDUFB4, NDUFB5, NDUFB6, NDUFB8, NDUFB9, NDUFC1, NDUFC2, NDUFS1, NDUFS3, NDUFS4, NDUFS6, NDUFS7, NDUFS8, NDUFV3, PLCB1, PLCB4, POLR2D, POLR2F, POLR2J, POLR2L, PPID, SDHA, SLC25A4, SLC25A6, SOD2, TAF4, TBP, TBPL1, TFAM, UQCR10, UQCR11, UQCRFS1, UQCRH, VDAC3", "KEGG", "1.76", "0.15"], ["Oxidative phosphorylation", 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PSMA6, PSMA7, PSMB1, PSMB2, PSMB3, PSMC1, PSMC2, PSMC3, PSMC5, PSMD1, PSMD10, PSMD3, PSMD5, RPS27A, SEC61B, SEC61G, TAP1, UBA52", "Reactome", "1.74", "0.18"], ["Alzheimers disease", "NDUFB6, CYCS, NDUFB3, NDUFA8, UQCR11, NDUFC2, ATP5F1, ATP5E, NDUFB5, UQCR10, COX4I1, COX6A1, COX7C, NDUFB10, NDUFB1, CASP8, NDUFV3, NDUFA6, ATP5H, COX7A2, RYR3, NDUFA2, NDUFC1, NDUFS1, NDUFA1, SDHA, NDUFB8, NDUFA4, NDUFA5, APAF1, UQCRH, ATP5O, NDUFA7, NDUFS6, NDUFS4, ATP5D, ATP5C1, NDUFB9, CACNA1D, NDUFS8, NDUFS3, NDUFS7, CASP3, COX8A, COX6C, COX5A, NDUFA10, ATP2A1, COX7A2L, TNFRSF1A, UQCRFS1, PSEN1, NDUFB4, IL1B, PLCB1, NCSTN, PLCB4", "KEGG", "1.74", "0.19"], ["Parkinsons disease", "APAF1, ATP5C1, ATP5D, ATP5E, ATP5F1, ATP5H, ATP5O, CASP3, COX4I1, COX5A, COX6A1, COX6C, COX7A2, COX7A2L, COX7C, COX8A, CYCS, GPR37, NDUFA1, NDUFA10, NDUFA2, NDUFA4, NDUFA5, NDUFA6, NDUFA7, NDUFA8, NDUFB1, NDUFB10, NDUFB3, NDUFB5, NDUFB6, NDUFB8, NDUFB9, NDUFC1, NDUFC2, NDUFS1, NDUFS3, NDUFS4, NDUFS6, NDUFS7, NDUFS8, NDUFV3, 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and heat production by uncoupling proteins", "ATP5C1, ATP5D, ATP5E, ATP5F1, ATP5H, ATP5I, ATP5J2, ATP5O, COX4I1, COX5A, COX6A1, COX6C, COX7A2L, COX7C, COX8A, CYCS, NDUFA1, NDUFA10, NDUFA12, NDUFA2, NDUFA4, NDUFA5, NDUFA6, NDUFA7, NDUFA8, NDUFB1, NDUFB10, NDUFB3, NDUFB4, NDUFB5, NDUFB6, NDUFB8, NDUFB9, NDUFC1, NDUFC2, NDUFS1, NDUFS3, NDUFS4, NDUFS6, NDUFS7, NDUFS8, NDUFV3, SDHA, UCP3, UQCR11, UQCRFS1, UQCRH", "Reactome", "1.83", "0.23"], ["Translation", "EEF1B2, EIF2B1, EIF2B2, EIF2S1, EIF2S2, EIF2S3, EIF3D, EIF3H, EIF3I, EIF3J, EIF4EBP1, EIF4H, EIF5B, RPL10A, RPL11, RPL13, RPL14, RPL18A, RPL19, RPL21, RPL22, RPL23A, RPL24, RPL26L1, RPL27, RPL27A, RPL29, RPL30, RPL32, RPL35, RPL35A, RPL36, RPL36A, RPL37, RPL37A, RPL38, RPL39, RPL5, RPL6, RPL7, RPL8, RPLP1, RPLP2, RPN1, RPS10, RPS11, RPS14, RPS15, RPS15A, RPS16, RPS2, RPS20, RPS23, RPS24, RPS25, RPS26, RPS27A, RPS28, RPS29, RPS3, RPS3A, RPS4X, RPS6, RPS7, RPS8, RPSA, SEC61B, SEC61G, SPCS1, SPCS2, SPCS3, SRP19, SRP72, SSR3, UBA52", "Reactome", "1.69", "0.24"], ["ER phagosome pathway", "PSMA1, PSMA2, PSMA3, PSMA5, PSMA6, PSMA7, PSMB1, PSMB2, PSMB3, PSMC1, PSMC2, PSMC3, PSMC5, PSMD1, PSMD10, PSMD3, PSMD5, RPS27A, SEC61B, SEC61G, TAP1, UBA52", "Reactome", "1.67", "0.25"]], "row_count": 14, "column_count": 5, "numeric_cells": 37, "header_rows": 1, "locator": "section[15]/table-wrap[1]#table-1"}}, {"id": "asset:table:pmid:29967729:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:87f9e0f0ffe8ee8f010e2ebe6563b2508b0030532b0c9843907cf09e63674195", "bytes": 3655, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[16]/table-wrap[1]#table-2", "version": null, "note": "Summary statistics for clusters of pathways enriched during FDMI and normal development.Mean Normalised Enrichment Score (NES), false discovery rate (FDR) and signal strength statistic (Signal) for the biological pathways implicated by GSEA in control and FDM. Normal eye development implicated 10 cluster of pathways showing average signal strength while form-deprivation induction implicated 18 clusters of pathways. Pathways shown here only include clustered pathways as represented in Figs. 3 and 4 and do not include pathways that were unclustered. Further detail on the unclustered pathways can be found in File 1. The NES reflects the degree to which a set of genes is overrepresented at either the top or bottom of a ranked list of genes while also taking into account differences in pathway size (i.e., geneset size). NES is the primary statistic for examining enrichment results, and for comparing results across pathways. The percentage signal strength statistic reflects the proportion of the core set of genes that contribute most to a given pathway’s enrichment by accounting for particular genes position in the ranked list. A high signal strength indicates that the genes within a pathway are located close to the top (positive NES) or bottom (negative NES) of the ranked gene list. If the core genes are spread throughout the ranked list, then the signal strength decreases towards zero (Mootha et al., 2003; Subramanian et al., 2005).", "structure": {"pmcid": "PMC6026464", "section_index": 16, "section_title": "Enrichment analysis for long-term FDM induction (FDMI) and recovery (FDMR)", "row_count": 24, "column_count": 9}, "table": {"label": "Table 2", "caption": "Summary statistics for clusters of pathways enriched during FDMI and normal development.Mean Normalised Enrichment Score (NES), false discovery rate (FDR) and signal strength statistic (Signal) for the biological pathways implicated by GSEA in control and FDM. Normal eye development implicated 10 cluster of pathways showing average signal strength while form-deprivation induction implicated 18 clusters of pathways. Pathways shown here only include clustered pathways as represented in Figs. 3 and 4 and do not include pathways that were unclustered. Further detail on the unclustered pathways can be found in File 1. The NES reflects the degree to which a set of genes is overrepresented at either the top or bottom of a ranked list of genes while also taking into account differences in pathway size (i.e., geneset size). NES is the primary statistic for examining enrichment results, and for comparing results across pathways. The percentage signal strength statistic reflects the proportion of the core set of genes that contribute most to a given pathway’s enrichment by accounting for particular genes position in the ranked list. A high signal strength indicates that the genes within a pathway are located close to the top (positive NES) or bottom (negative NES) of the ranked gene list. If the core genes are spread throughout the ranked list, then the signal strength decreases towards zero (Mootha et al., 2003; Subramanian et al., 2005).", "rows": [["Cluster", "Control", "FDMI"], ["", "Pathways in cluster", "NES", "FDR q-value", "Signal", "Pathways in cluster", "NES", "FDR q-value", "Signal"], ["Cell cycle, mitotic", "5", "−2.233", "0.019", "31%", "3", "−2.253", "0.009", "98%"], ["Cell maintenance & survival", "–", "–", "–", "–", "28", "−2.180", "0.014", "117%"], ["Clatherin-mediated endocytosis (CME)", "–", "–", "–", "–", "2", "−2.014", "0.032", "81%"], ["Complement and coagulation cascades (CCC)", "–", "–", "–", "–", "2", "2.708", "0.003", "140%"], ["Cytochrome p450", "2", "2.247", "0.025", "47%", "5", "2.629", "0.002", "133%"], ["Cytokine pathways", "2", "2.717", "0.002", "40%", "–", "–", "–", "–"], ["Neuron structure/growth", "–", "–", "–", "–", "5", "−2.321", "0.007", "80%"], ["Fatty acid (FA) metabolism", "–", "–", "–", "–", "2", "−1.886", "0.032", "84%"], ["Glucosaminoglycan (GAG) metabolism", "4", "2.121", "0.029", "40%", "–", "–", "–", "–"], ["Ion channel transport", "–", "–", "–", "–", "2", "−2.331", "0.007", "99%"], ["Mitochondrial energy metabolism", "–", "–", "–", "–", "7", "2.396", "0.005", "47%"], ["Neurotransmission", "5", "−2.522", "0.011", "37%", "8", "−2.423", "0.007", "103%"], ["Peroxisome", "2", "−2.221", "0.017", "40%", "–", "–", "–", "–"], ["Phospholipid metabolism", "2", "−2.134", "0.026", "28%", "3", "−1.939", "0.027", "57%"], ["Signal transduction, growth factors (GF)", "–", "–", "–", "–", "4", "−1.984", "0.021", "66%"], ["Signal transduction, g-protein coupled receptors (GPCR)", "7", "2.572", "0.019", "52%", "7", "2.683", "0.010", "122%"], ["Signal transduction, mitogen-activated protein kinases (MAPK)", "–", "–", "–", "–", "4", "−1.931", "0.028", "67%"], ["Signal transduction, nerve growth factor (NGF)", "–", "–", "–", "–", "5", "−2.195", "0.014", "84%"], ["Transcription", "–", "–", "–", "–", "10", "−2.218", "0.013", "120%"], ["Translation", "–", "–", "–", "–", "8", "2.731", "0.001", "46%"], ["Ubiquitin-mediated proteolysis", "3", "−2.491", "0.006", "39%", "–", "–", "–", "–"], ["Vesicle-mediated transport", "3", "−2.152", "0.025", "40%", "3", "−2.097", "0.013", "103%"]], "row_count": 24, "column_count": 9, "numeric_cells": 113, "header_rows": 2, "locator": "section[16]/table-wrap[1]#table-2"}}], "gaps": ["asset:data:geo:GSE6543 not downloaded", "asset:data:geo:GSE6543 licence not read", "asset:data:geo:GSE89325 not downloaded", "asset:data:geo:GSE89325 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": null, "specific": null, "label": "Gene Set Enrichment Analysis (GSEA)", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "reordered", "quote": "“The Broad Institute’s Gene Set Enrichment Analysis (GSEA) software was used to determine whether a priori defined sets of genes were significantly enriched (Mootha et al., 2003; Subramanian et al., 2005) during the induction and recovery of FD.”"}}], "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": "method", "blocked_on": "method:not_determinable", "axes": {"method": {"tier": "R4", "expressible": false, "required_operations": [], "missing_operations": [], "basis": "The reader quoted the method the paper names (Gene Set Enrichment Analysis (GSEA)), 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. 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