Altered Gene Expression in the Testis of Infertile Patients with Nonobstructive Azoospermia.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34221106", "kind": "science-record", "revision": 8, "content_hash": "sha256:7f078feeee1c3ef8eed4507fbbc0e055b61fc0cf6e85902e6ef5dfd44db738ef", "created_at": "2026-11-01T15:41:41Z", "updated_at": "2026-11-01T22:47:00Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Altered Gene Expression in the Testis of Infertile Patients with Nonobstructive Azoospermia.", "doi": "10.1155/2021/5533483", "pmid": "34221106", "authors": ["Zhiqiang Wang", "Zhongjun Ding", "Yan Guan", "Chunhui Liu", "Linjun Wang", "Wensheng Shan", "Jie Yang"], "journal": "Computational and mathematical methods in medicine", "year": 2021, "abstract": "BACKGROUND: The molecular mechanism of nonobstructive azoospermia (NOA) remains unclear. The aim of this study was to identify gene expression changes in NOA patients and to explore potential biomarkers and therapeutic targets.\nMETHODS: The gene expression profiles of GSE45885 and GSE145467 were collected from the Gene Expression Omnibus (GEO) database, and the differences between NOA and normal spermatogenesis were analyzed. Enrichment analysis was performed to explore biological functions for common differentially expressed genes (DEGs) in GSE45885 and GSE145467. Coexpression analysis of DEGs in GSE45885 was performed, and two modules with the highest correlation with NOA were screened. Key genes were then screened from the intersection genes of the two modules and common DEGs and PPI network. The expression of key genes was validated by quantitative real-time polymerase chain reaction (qRT-PCR) experiments. Finally, through miRTarBase, miRDB, and RAID, the miRNAs were predicted to regulate key genes, respectively.\nRESULTS: A total of 345 common DEGs were identified and they were mainly related to spermatogenesis, insulin signaling pathway. Coexpression analysis of DEGs in GSE45885 yielded eight modules; MEblack and MEturquoise had the highest correlation with NOA. Six genes in MEturquoise and RNF141 in MEblack were identified as key genes. qRT-PCR experiments validated the differential expression of key genes between NOA and control. Furthermore, RNF141 was regulated by the largest number of miRNAs.\nCONCLUSION: Our findings suggest that the significant change expression of key genes may be potential markers and therapeutic targets of NOA and may have some impact on the development of NOA.", "claims": [{"id": "claim-method", "statement": "Differential expression analysis was performed using the limma R package [21, 22] to identify differentially expressed genes (DEGs) between NOA and normal spermatogenesis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34221106", "locator": "sections[4] \"2.2. Difference Analysis\" paragraph 2", "quote": "Differential expression analysis was performed using the limma R package [21, 22] to identify differentially expressed genes (DEGs) between NOA and normal spermatogenesis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The corresponding data can be found in GSE45885 and GSE145467.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34221106", "locator": "sections[19] \"Data Availability\" paragraph 2", "quote": "The corresponding data can be found in GSE45885 and GSE145467."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:34221106"], "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:GSE145467"], "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:GSE145467"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34221106", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2021/5533483", "sha256": "sha256:99263b696e23ecdadec10b9e772f6d6debf0b68fc45b1074b804e3d14b8cabe4", "bytes": 17199, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2021/5533483", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8211532", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE145467", "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=GSE145467", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE145467", "version": null, "note": "The corresponding data can be found in GSE45885 and GSE145467.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The corresponding data can be found in GSE45885 and GSE145467.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4318655", "GSM4318656", "GSM4318657", "GSM4318658", "GSM4318660", "GSM4318662", "GSM4318665", "GSM4318668", "GSM4318670", "GSM4318672", "GSM4318673", "GSM4318674", "GSM4318675", "GSM4318676", "GSM4318677", "GSM4318678", "GSM4318679", "GSM4318680", "GSM4318681", "GSM4318682"], "sample_count": 20, "group_sizes": null, "group_sizes_basis": null, "platform": "4133", "taxon": "Homo sapiens", "title": "Transcriptome changes in patients with severely impaired spermatogenesis", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE45885", "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=GSE45885", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE45885", "version": null, "note": "The corresponding data can be found in GSE45885 and GSE145467.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The corresponding data can be found in GSE45885 and GSE145467.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1118241", "GSM1118242", "GSM1118243", "GSM1118244", "GSM1118245", "GSM1118246", "GSM1118247", "GSM1118248", "GSM1118249", "GSM1118250", "GSM1118251", "GSM1118252", "GSM1118253", "GSM1118254", "GSM1118255", "GSM1118256", "GSM1118257", "GSM1118258", "GSM1118259", "GSM1118260", "GSM1118261", "GSM1118262", "GSM1118263", "GSM1118264", "GSM1118265", "GSM1118266", "GSM1118267", "GSM1118268", "GSM1118269", "GSM1118270", "GSM1118271"], "sample_count": 31, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Potential biomarkers of non-obstructive azoospermia identified in microarray gene expression analysis", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE145467 not downloaded", "asset:data:geo:GSE145467 licence not read", "asset:data:geo:GSE45885 not downloaded", "asset:data:geo:GSE45885 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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": 1.0, "band": "verbatim", "quote": "Differential expression analysis was performed using the limma R package [21, 22] to identify differentially expressed genes (DEGs) between NOA and normal spermatogenesis."}}, {"id": "method-2", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Student's t-test"}}, {"id": "method-3", "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": "PPI"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "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": "R1", "reachable": true, "accessions": ["GSE45885", "GSE145467"], "resolved_accessions": ["GSE45885", "GSE145467"], "statements": ["The corresponding data can be found in GSE45885 and GSE145467."], "basis": "The paper names GSE45885, GSE145467 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:34221106", "data:geo:GSE145467"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE145467"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:31:50Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 14402, "completion_tokens": 1305, "cached_tokens": 784}}, "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:34221106", "type": "paper", "label": "pmid:34221106"}, {"id": "source:pmid:34221106", "type": "manuscript", "label": "PMID 34221106 full text"}, {"id": "data:geo:GSE145467", "type": "dataset", "label": "GEO GSE145467"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34221106", "type": "paper", "label": "pmid:34221106"}, {"id": "source:pmid:34221106", "type": "manuscript", "label": "PMID 34221106 full text"}, {"id": "data:geo:GSE145467", "type": "dataset", "label": "GEO GSE145467"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34221106", "type": "extraction", "used": ["source:pmid:34221106"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE145467", "type": "accession_resolution", "used": ["data:geo:GSE145467"], "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:34221106", "parent_hash": "sha256:a89c11ed68af488a7ebf2b11c5165e67dfb8ef3a2f34c45012d2ec698969ccfb", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE145467 licence not read", "asset:data:geo:GSE145467 not downloaded", "asset:data:geo:GSE45885 licence not read", "asset:data:geo:GSE45885 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Differential expression analysis was performed using the limma R package [21, 22] to identify differentially expressed genes (DEGs) between NOA and normal spermatogenesis."], "order_basis": "analysis_only", "id": "assay:1"}]}