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pmid:36686439

Transcriptomic profiling of hepatic tissues for drug metabolism genes in nonalcoholic fatty liver disease: A study of human and animals.

Li Chen · Lu Chen · Xu Li · Lin Qin · Yan Zhu · Qianru Zhang · Daopeng Tan · Yuqi He · Yu-He Wang

Frontiers in endocrinology · 2022 doi:10.3389/fendo.2022.1034494

Paper

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Experiment

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Data

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title
Transcriptomic profiling of hepatic tissues for drug metabolism genes in nonalcoholic fatty liver disease: A study of human and animals.
doi
10.3389/fendo.2022.1034494
pmid
36686439
authors array · 9 items
[0]
Li Chen
[1]
Lu Chen
[2]
Xu Li
[3]
Lin Qin
[4]
Yan Zhu
[5]
Qianru Zhang
[6]
Daopeng Tan
[7]
Yuqi He
[8]
Yu-He Wang
journal
Frontiers in endocrinology
year
2022
abstract
Background: Drug metabolism genes are involved in the in vivo metabolic processing of drugs. In previous research, we found that a high-fat diet affected the transcript levels of mouse hepatic genes responsible for drug metabolism. Aims: Our research intends to discover the drug metabolism genes that are dysregulated at the transcriptome level in nonalcoholic fatty liver disease (NAFLD). Methods: We analyzed the transcriptome for drug metabolism genes of 35 human liver tissues obtained during laparoscopic cholecystectomy. Additionally, we imported transcriptome data from mice fed a high-fat diet in previous research and two open-access Gene Expression Omnibus (GEO) datasets (GSE63067 and GSE89632). Then, using quantitative real-time polymerase chain reaction (qRT-PCR), we cross-linked the differentially expressed genes (DEGs) in clinical and animal samples and validated the common genes. Results: In this study, we identified 35 DEGs, of which 33 were up-regulated and two were down-regulated. Moreover, we found 71 DEGs (39 up- and 32 down-regulated), 276 DEGs (157 up- and 119 down-regulated), and 158 DEGs (117 up- and 41 down-regulated) in the GSE63067, GSE89632, and high-fat diet mice, respectively. Of the 35 DEGs, nine co-regulated DEGs were found in the Venn diagram (CYP20A1, CYP2U1, SLC9A6, SLC26A6, SLC31A1, SLC46A1, SLC46A3, SULT1B1, and UGT2A3). Conclusion: Nine significant drug metabolism genes were identified in NAFLD. Future research should investigate the impacts of these genes on drug dose adjustment in patients with NAFLD. Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR2100041714.
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Nine significant drug metabolism genes were identified in NAFLD.
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Transcriptomic profiling of hepatic tissues for drug metabo
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etabolism genes that are dysregulated at the transcriptome level in nonalcoholic fatty liver disease (N
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c cholecystectomy. Additionally, we imported transcriptome data from mice fed a high-fat diet in previo
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ize and high false positive rate of a single transcriptome analysis, it may be difficult to obtain reli
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d: Drug metabolism genes are involved in the in vivo metabolic processing of drugs. In previous r
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develop a list of 612 drug metabolism genes in mice (9). Meanwhile, in the present study, from a
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36686439", "kind": "science-record", "revision": 3, "content_hash": "sha256:c011d94da912b036fd2791168f23359cf17cc6f94aa5b097678a758f683bc0de", "created_at": "2026-11-01T19:01:14Z", "updated_at": "2026-11-01T22:08:37Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Transcriptomic profiling of hepatic tissues for drug metabolism genes in nonalcoholic fatty liver disease: A study of human and animals.", "doi": "10.3389/fendo.2022.1034494", "pmid": "36686439", "authors": ["Li Chen", "Lu Chen", "Xu Li", "Lin Qin", "Yan Zhu", "Qianru Zhang", "Daopeng Tan", "Yuqi He", "Yu-He Wang"], "journal": "Frontiers in endocrinology", "year": 2022, "abstract": "Background: Drug metabolism genes are involved in the in vivo metabolic processing of drugs. In previous research, we found that a high-fat diet affected the transcript levels of mouse hepatic genes responsible for drug metabolism.\nAims: Our research intends to discover the drug metabolism genes that are dysregulated at the transcriptome level in nonalcoholic fatty liver disease (NAFLD).\nMethods: We analyzed the transcriptome for drug metabolism genes of 35 human liver tissues obtained during laparoscopic cholecystectomy. Additionally, we imported transcriptome data from mice fed a high-fat diet in previous research and two open-access Gene Expression Omnibus (GEO) datasets (GSE63067 and GSE89632). Then, using quantitative real-time polymerase chain reaction (qRT-PCR), we cross-linked the differentially expressed genes (DEGs) in clinical and animal samples and validated the common genes.\nResults: In this study, we identified 35 DEGs, of which 33 were up-regulated and two were down-regulated. Moreover, we found 71 DEGs (39 up- and 32 down-regulated), 276 DEGs (157 up- and 119 down-regulated), and 158 DEGs (117 up- and 41 down-regulated) in the GSE63067, GSE89632, and high-fat diet mice, respectively. Of the 35 DEGs, nine co-regulated DEGs were found in the Venn diagram (CYP20A1, CYP2U1, SLC9A6, SLC26A6, SLC31A1, SLC46A1, SLC46A3, SULT1B1, and UGT2A3).\nConclusion: Nine significant drug metabolism genes were identified in NAFLD. Future research should investigate the impacts of these genes on drug dose adjustment in patients with NAFLD.\nClinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR2100041714.", "claims": [{"id": "claim-method", "statement": "The screening criteria for DEGs were as follows: P-value <0.05 and |fold change|>1.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36686439", "locator": "sections[13] \"3.3 Differentially expressed genes\" paragraph 2", "quote": "The screening criteria for DEGs were as follows: P-value <0.05 and |fold change|>1."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The data presented in the study are deposited in the ArrayExpress repository, accession number E-MTAB-12445. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36686439", "locator": "sections[18] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The data presented in the study are deposited in the ArrayExpress repository, accession number E-MTAB-12445. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material ."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Nine significant drug metabolism genes were identified in NAFLD.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36686439", "locator": "sections[0] \"Abstract\" paragraph 5", "quote": "Nine significant drug metabolism genes were identified in NAFLD."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Nine significant drug metabolism genes were identified in NAFLD.", "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:36686439"], "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:E-MTAB-12445"], "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:E-MTAB-12445"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36686439", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fendo.2022.1034494", "sha256": "sha256:19d14b727d1e922c5338c6b0989603e1b545cb04ac96d688ab53a5f77360e4f3", "bytes": 47763, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fendo.2022.1034494", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9845619", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:E-MTAB-12445", "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=E-MTAB-12445", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "E-MTAB-12445", "version": null, "note": "The datasets presented in this study can be found in online repositories. The data presented in the study are deposited in the ArrayExpress repository, accession number E-MTAB-12445. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. The data presented in the study are deposited in the ArrayExpress repository, accession number E-MTAB-12445. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": null, "resolution_checked_at": "2026-11-01T18:46:41Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE63067", "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=GSE63067", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE63067", "version": null, "note": "The datasets presented in this study can be found in online repositories. The data presented in the study are deposited in the ArrayExpress repository, accession number E-MTAB-12445. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. The data presented in the study are deposited in the ArrayExpress repository, accession number E-MTAB-12445. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1539877", "GSM1539878", "GSM1539879", "GSM1539880", "GSM1539881", "GSM1539882", "GSM1539883", "GSM1539884", "GSM1539885", "GSM1539886", "GSM1539887", "GSM1539888", "GSM1539889", "GSM1539890", "GSM1539891", "GSM1539892", "GSM1539893", "GSM1539894"], "sample_count": 18, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Expression data from human non-alcoholic fatty liver disease stages", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE89632", "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=GSE89632", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE89632", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2385720", "GSM2385721", "GSM2385722", "GSM2385723", "GSM2385724", "GSM2385725", "GSM2385726", "GSM2385727", "GSM2385728", "GSM2385729", "GSM2385730", "GSM2385731", "GSM2385732", "GSM2385733", "GSM2385734", "GSM2385735", "GSM2385736", "GSM2385737", "GSM2385738", "GSM2385739", "GSM2385740", "GSM2385741", "GSM2385742", "GSM2385743", "GSM2385744", "GSM2385745", "GSM2385746", "GSM2385747", "GSM2385748", "GSM2385749", "GSM2385750", "GSM2385751", "GSM2385752", "GSM2385753", "GSM2385754", "GSM2385755", "GSM2385756", "GSM2385757", "GSM2385758", "GSM2385759", "GSM2385760", "GSM2385761", "GSM2385762", "GSM2385763", "GSM2385764", "GSM2385765", "GSM2385766", "GSM2385767", "GSM2385768", "GSM2385769", "GSM2385770", "GSM2385771", "GSM2385772", "GSM2385773", "GSM2385774", "GSM2385775", "GSM2385776", "GSM2385777", "GSM2385778", "GSM2385779", "GSM2385780", "GSM2385781", "GSM2385782"], "sample_count": 63, "group_sizes": null, "group_sizes_basis": null, "platform": "14951", "taxon": "Homo sapiens", "title": "Genome-wide analysis of hepatic gene expression in patients with non-alcoholic fatty liver disease  and in healthy donors in relation to hepatic fatty acid composition and other nutritional factors", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:E-MTAB-12445 not downloaded", "asset:data:geo:E-MTAB-12445 licence not read", "asset:data:geo:GSE63067 not downloaded", "asset:data:geo:GSE63067 licence not read", "asset:data:geo:GSE89632 not downloaded", "asset:data:geo:GSE89632 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "principal_component_analysis", "specific": "pca", "label": "Principal component analysis", "dsl_operations": ["pca_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["wide_numeric_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "PCA"}}, {"id": "method-2", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 0.8, "band": "high", "quote": "limma"}}, {"id": "method-3", "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-4", "family": null, "specific": null, "label": "Differentially expressed genes were screened using P-value and absolute fold-change thresholds with volcano plots.", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The screening criteria for DEGs were as follows: P-value <0.05 and |fold change|>1."}}], "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": ["pca_fit"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: pca."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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Additionally, we imported transcriptome data from mice fed a high-fat diet in previo", "ize and high false positive rate of a single transcriptome analysis, it may be difficult to obtain reli"], "order_basis": "paper_text_order:0", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["d: Drug metabolism genes are involved in the in vivo metabolic processing of drugs. In previous r", "h-fat diet affected the transcript levels of mouse hepatic genes responsible for drug metabolis", "develop a list of 612 drug metabolism genes in mice (9). Meanwhile, in the present study, from a", "oups are in red, and the HFD groups are blue in the mouse data. 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