Integrated Analysis of Multiple Microarrays Based on Raw Data Identified Novel Gene Signatures in Recurrent Implantation Failure.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35197930", "kind": "science-record", "revision": 5, "content_hash": "sha256:84da67f279ca84623598f256aaa98b428f8dbf00a70fbbd7da6361cf983740c8", "created_at": "2026-11-01T17:36:57Z", "updated_at": "2026-11-01T22:05:57Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrated Analysis of Multiple Microarrays Based on Raw Data Identified Novel Gene Signatures in Recurrent Implantation Failure.", "doi": "10.3389/fendo.2022.785462", "pmid": "35197930", "authors": ["Hong Zeng", "Yu Fu", "Lang Shen", "Song Quan"], "journal": "Frontiers in endocrinology", "year": 2022, "abstract": "Background: Recurrent implantation failure (RIF) is an intricate complication following IVF-ET, which refers to the situation that good-quality embryos repeatedly fail to implant following two or more IVF cycles. Intrinsic molecular mechanisms underlying RIF have not yet been fully elucidated. With enormous improvement in high-throughput technologies, researchers screened biomarkers for RIF using microarray. However, the findings of published studies are inconsistent. An integrated study on the endometrial molecular determinants of implantation will help to improve pregnancy outcomes.\nObjective: To identify robust differentially expressed genes (DEGs) and hub genes in endometrium associated with RIF, and to investigate the diagnostic role of hub genes in RIF.\nMethods: Raw data from five GEO microarrays regarding RIF were analyzed. Integrated genetic expression analyses were performed using the Robust Rank Aggregation method to identify robust DEGs. Enrichment analysis and protein-protein interaction (PPI) analysis were further performed with the robust DEGs. Cytohubba was used to screen hub genes based on the PPI network. GSE111974 was used to validate the expression and diagnostic role of hub genes in RIF.\nResults: 1532 Robust DEGs were identified by integrating four GEO datasets. Enrichment analysis showed that the robust DEGs were mainly enriched in processes associated with extracellular matrix remodeling, adhesion, coagulation, and immunity. A total of 18 hub genes (HMGCS1, SQLE, ESR1, LAMC1, HOXB4, PIP5K1B, GNG11, GPX3, PAX2, TF, ALDH6A1, IDH1, SALL1, EYA1, TAGLN, TPD52L1, ST6GALNAC1, NNMT) were identified. 10 of the 18 hub genes were significantly differentially expressed in RIF patients as validated by GSE111974. The 10 hub genes (SQLE, LAMC1, HOXB4, PIP5K1B, PAX2, ALDH6A1, SALL1, EYA1, TAGLN, ST6GALNAC1) were effective in predicting RIF with an accuracy rate of 85%, specificity rate of 100%, and sensitivity rate of 88.9%.\nConclusions: Our integrated analysis identified novel robust DEGs and hub genes in RIF. The hub genes were effective in predicting RIF and will contribute to the understanding of comprehensive molecular mechanisms in RIF pathogenesis.", "claims": [{"id": "claim-method", "statement": "The “RobustRankAggregation” R package (15) was used to integrate the ranked gene lists of DEGs to find the robust DEGs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35197930", "locator": "sections[6] \"RRA Analysis of DEGs From Different GSEs\" paragraph 2", "quote": "The “RobustRankAggregation” R package (15) was used to integrate the ranked gene lists of DEGs to find the robust DEGs."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. 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:35197930", "locator": "sections[21] \"Data Availability Statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. 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": "Robust Rank Aggregation of four GEO endometrial microarray datasets identified 1,532 robust DEGs and 18 hub genes, and a 10-hub-gene model predicted recurrent implantation failure with 85% accuracy, 100% specificity, 88.9% sensitivity, and an AUC of 0.980.", "kind": "quantitative", "target": {"value": 0.98, "unit": "auc", "tolerance": null, "source": "The ROC analysis showed that the AUC is 0.980 ( Figure 7 )."}, "evidence": [{"asset": "source:pmid:35197930", "locator": "sections[15] \"Integrative Analysis of DEGs From Different GSEs\" paragraph 2", "quote": "1532 significantly robust DEGs were identified by the RRA analysis with the criteria of adjusted p-value<0.05."}, {"asset": "source:pmid:35197930", "locator": "sections[17] \"Protein-Protein Interaction (PPI) Analysis and Identification of Hub Genes\" paragraph 2", "quote": "Finally, 18 genes (HMGCS1, SQLE, ESR1, LAMC1, HOXB4, PIP5K1B, GNG11, GPX3, PAX2, TF, ALDH6A1, IDH1, SALL1, EYA1, TAGLN, TPD52L1, ST6GALNAC1, NNMT) were determined as the hub genes."}, {"asset": "source:pmid:35197930", "locator": "sections[19] \"The Diagnostic Role of Hub Genes in RIF\" paragraph 2", "quote": "In the validation set, the prediction model showed an accuracy rate of 85%, specificity rate of 100%, and sensitivity rate of 88.9%."}, {"asset": "source:pmid:35197930", "locator": "sections[19] \"The Diagnostic Role of Hub Genes in RIF\" paragraph 2", "quote": "The ROC analysis showed that the AUC is 0.980 ( Figure 7 )."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Robust Rank Aggregation of four GEO endometrial microarray datasets identified 1,532 robust DEGs and 18 hub genes, and a 10-hub-gene model predicted recurrent implantation failure with 85% accuracy, 100% specificity, 88.9% sensitivity, and an AUC of 0.980.", "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:35197930"], "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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However, the findings of published studies", "y-material Supplementary Table 1DEGs in each microarray dataset.Click here for additional data file."], "order_basis": "paper_text_order:485", "id": "assay:1"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Mann-Whitney"], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}