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pmid:30949322

Investigation of health benefits of cocoa in human colorectal cancer cell line, HT-29 through interactome analysis.

Mona Zamanian-Azodi · Mostafa Rezaei-Tavirani

Gastroenterology and hepatology from bed to bench · 2019

Paper

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Experiment

complete

Data

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Analysis

partial

Execution

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Investigation of health benefits of cocoa in human colorectal cancer cell line, HT-29 through interactome analysis.
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null
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30949322
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Mona Zamanian-Azodi
[1]
Mostafa Rezaei-Tavirani
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Gastroenterology and hepatology from bed to bench
year
2019
abstract
AIM: This bioinformatics study aims to identify the potential key genes influenced by cocoa extraction treatment on colon cancer cell line HT-29 after 24h. BACKGROUND: Cocoa consumption has been claimed to have beneficial effects on human body including protection against diseases such as different types of cancers. However, the mechanisms behind this is still remained to be studied. METHODS: The microarray dataset (GSE94154) from GEO, was the source for differentially expressed genes (DEGs) extraction through GEO2R analysis. The comparison was between 3 controls of colorectal cell line HT-29 and 3 ones incubated with 500 µg cocoa extraction after 24 h. Afterwards, the top significant DEGs were assigned for protein-protein interaction network construction and analysis by Cytoscape v 3.7.0. and the related applications. RESULTS: The findings indicate that there are 222 up-regulated and 28 down-regulated genes among 250 top-ranked DEGs in cocoa incubated group. What is more, centrality analysis of the DEGs network identified 10 hub-bottlenecks that ISG15, MX 1, and STAT1 were among the significant differential expression genes with the contribution in type 1 interferon signaling pathway, positive regulation of erythrocyte differentiation, and negative regulation of viral genome replication. CONCLUSION: In conclusion, the underlying mechanisms of cocoa treatment could be clarified by its up-regulatory and modulatory effect on prominent genes of tumor suppressor family. In other words, valuable clues for future clinical studies of cocoa health benefits are highlighted as anticancer agent in this study once validation studies are carried out.
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The microarray dataset (GSE94154) from GEO, was the source for differentially expressed genes (DEGs) extraction through GEO2R analysis. The comparison was between 3 controls of colorectal cell line HT-29 and 3 ones incubated with 500 µg cocoa extraction after 24 h. The study identifies with Series Accession: GSE94154 and Platform: GPL570 that was conducted by Ciudad CJ, et al. in 2018 entitled, “Gene expression after 24h Cocoa Extract incubation in HT29 cells (Homo sapiens)”.
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The microarray dataset (GSE94154) from GEO, was the source for differentially expressed genes (DEGs) extraction through GEO2R analysis.
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The comparison was between 3 controls of colorectal cell line HT-29 and 3 ones incubated with 500 µg cocoa extraction after 24 h.
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Gene expression after 24h Cocoa Extract incubation in HT29 cells
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Abbreviations S-DE-HB, FC, FDR, and NS indicate significant differentially expressed hub-bottlenecks, fold change, false discovery rate, and number of spots, respectively
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The microarray dataset (GSE94154) from GEO, was the source for differentially expressed genes (DEGs) extraction through GEO2R analysis. The comparison was between 3 controls of colorectal cell line HT-29 and 3 ones incubated with 500 µg cocoa extraction after 24 h. The study identifies with Series Accession: GSE94154 and Platform: GPL570 that was conducted by Ciudad CJ, et al. in 2018 entitled, “Gene expression after 24h Cocoa Extract incubation in HT29 cells (Homo sapiens)”.
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However, the mechanisms behind this is still remained to be studied.\nMETHODS: The microarray dataset (GSE94154) from GEO, was the source for differentially expressed genes (DEGs) extraction through GEO2R analysis. The comparison was between 3 controls of colorectal cell line HT-29 and 3 ones incubated with 500 µg cocoa extraction after 24 h. Afterwards, the top significant DEGs were assigned for protein-protein interaction network construction and analysis by Cytoscape v 3.7.0. and the related applications.\nRESULTS: The findings indicate that there are 222 up-regulated and 28 down-regulated genes among 250 top-ranked DEGs in cocoa incubated group. What is more, centrality analysis of the DEGs network identified 10 hub-bottlenecks that ISG15, MX 1, and STAT1 were among the significant differential expression genes with the contribution in type 1 interferon signaling pathway, positive regulation of erythrocyte differentiation, and negative regulation of viral genome replication.\nCONCLUSION: In conclusion, the underlying mechanisms of cocoa treatment could be clarified by its up-regulatory and modulatory effect on prominent genes of tumor suppressor family. In other words, valuable clues for future clinical studies of cocoa health benefits are highlighted as anticancer agent in this study once validation studies are carried out.", "claims": [{"id": "claim-method", "statement": "In GEO2R, at first data were preprocessed via box plot analysis and then the DEGs were analyzed by the application of t-test, and the top ranked genes (250 significant ones) were screened and assigned by the consideration of adj. 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This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE94154"], "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:GSE94154"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:30949322", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": null, "sha256": "sha256:7b37b37d10809fc6161760fea5a05dda03fb2c9d9ff72722d6adbba7e3c3b42a", "bytes": 23064, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "30949322", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6441487", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE94154", "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=GSE94154", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE94154", "version": null, "note": "The microarray dataset (GSE94154) from GEO, was the source for differentially expressed genes (DEGs) extraction through GEO2R analysis. The comparison was between 3 controls of colorectal cell line HT-29 and 3 ones incubated with 500 µg cocoa extraction after 24 h. The study identifies with Series Accession: GSE94154 and Platform: GPL570 that was conducted by Ciudad CJ, et al. in 2018 entitled, “Gene expression after 24h Cocoa Extract incubation in HT29 cells (Homo sapiens)”.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The microarray dataset (GSE94154) from GEO, was the source for differentially expressed genes (DEGs) extraction through GEO2R analysis. The comparison was between 3 controls of colorectal cell line HT-29 and 3 ones incubated with 500 µg cocoa extraction after 24 h. The study identifies with Series Accession: GSE94154 and Platform: GPL570 that was conducted by Ciudad CJ, et al. in 2018 entitled, “Gene expression after 24h Cocoa Extract incubation in HT29 cells (Homo sapiens)”.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM2471152", "GSM2471153", "GSM2471154", "GSM2471155", "GSM2471156", "GSM2471157"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Gene expression after 24h Cocoa Extract incubation in HT29 cells", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:30949322:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:03f1f53638771f33cbe6866b29a8ec05d0008c2899fd30df8a013c4224762f74", "bytes": 1053, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[1]#T1", "version": null, "note": "The list of hub-bottlenecks of network of colon cancer cell line HT-29 treated with cocoa extraction. BC refers to betweenness centrality", "structure": {"pmcid": "PMC6441487", "section_index": 3, "section_title": "Results", "row_count": 11, "column_count": 6}, "table": {"label": "Table 1", "caption": "The list of hub-bottlenecks of network of colon cancer cell line HT-29 treated with cocoa extraction. BC refers to betweenness centrality", "rows": [["R", "Display name", "Description", "Degree", "BC", "Query term"], ["1", "ISG15", "ISG15 ubiquitin-like modifier", "111", "0.02", "ISG15"], ["2", "STAT1", "signal transducer and activator of transcription 1, 91kDa", "105", "0.03", "STAT1"], ["3", "MX1", "myxovirus (influenza virus) resistance 1, interferon-inducible protein p78 (mouse)", "95", "0.02", "MX1"], ["4", "TP53", "tumor protein p53", "89", "0.04", "-"], ["5", "GAPDH", "glyceraldehyde-3-phosphate dehydrogenase", "87", "0.02", "-"], ["6", "PRDM10", "PR domain containing 10", "85", "0.03", "-"], ["7", "EGR1", "early growth response 1", "80", "0.02", "-"], ["8", "IL6", "interleukin 6 (interferon, beta 2)", "78", "0.02", "-"], ["9", "AKT1", "v-akt murine thymoma viral oncogene homolog 1", "76", "0.04", "-"], ["10", "TNF", "tumor necrosis factor", "76", "0.02", "-"]], "row_count": 11, "column_count": 6, "numeric_cells": 43, "header_rows": 1, "locator": "section[3]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:30949322:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:e694f6433e2328815c10de73c4afdf6464ac1cc06d9b8ccbf018296d65d1fd82", "bytes": 620, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[4]/table-wrap[1]#T2", "version": null, "note": "Abbreviations S-DE-HB, FC, FDR, and NS indicate significant differentially expressed hub-bottlenecks, fold change, false discovery rate, and number of spots, respectively", "structure": {"pmcid": "PMC6441487", "section_index": 4, "section_title": "Discussion", "row_count": 4, "column_count": 7}, "table": {"label": "Table 2", "caption": "Abbreviations S-DE-HB, FC, FDR, and NS indicate significant differentially expressed hub-bottlenecks, fold change, false discovery rate, and number of spots, respectively", "rows": [["Rank", "S-DE-HB", "Protein name", "Expression Condition", "FC", "FDR", "NS"], ["12", "MX1", "MX dynamin like GTPase 1", "Up", "4.5", "0.00007", "1"], ["211", "ISG15", "ISG15 ubiquitin-like modifier", "Up", "2.3", "0.0008", "1"], ["38", "STAT1", "signal transducer and activator of transcription 1", "UP", "2.3", "0.00014", "7"]], "row_count": 4, "column_count": 7, "numeric_cells": 16, "header_rows": 1, "locator": "section[4]/table-wrap[1]#T2"}}], "gaps": ["asset:data:geo:GSE94154 not downloaded", "asset:data:geo:GSE94154 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}, {"id": "method-2", "family": "network_analysis", "specific": "centrality", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "centrality"}}, {"id": "method-3", "family": null, "specific": null, "label": "t-test", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "In GEO2R, at first data were preprocessed via box plot analysis and then the DEGs were analyzed by the application of t-test, and the top ranked genes (250 significant ones) were screened and assigned by the consideration of adj. P-value via Benjamini and Hochberg correction method."}}], "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": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ppi_network."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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