Identification of Diagnostic Markers Correlated With HIV+ Immune Non-response Based on Bioinformatics Analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35004856", "kind": "science-record", "revision": 5, "content_hash": "sha256:6c9ed4b61db22f13c197eb99c9d257e615a4f532733ddce1b746985b6aebe7a5", "created_at": "2026-11-01T17:36:44Z", "updated_at": "2026-11-01T22:48:13Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Diagnostic Markers Correlated With HIV+ Immune Non-response Based on Bioinformatics Analysis.", "doi": "10.3389/fmolb.2021.809085", "pmid": "35004856", "authors": ["Ruojing Bai", "Zhen Li", "Yuying Hou", "Shiyun Lv", "Ran Wang", "Wei Hua", "Hao Wu", "Lili Dai"], "journal": "Frontiers in molecular biosciences", "year": 2021, "abstract": "Background: HIV-infected immunological non-responders (INRs) are characterized by their inability to reconstitute CD4+ T cell pools after antiretroviral therapy. The risk of non-AIDS-related diseases in INRs is increased, and the outcome and prognosis of INRs are inferior to that of immunological responders (IRs). However, few markers can be used to define INRs precisely. In this study, we aim to identify further potential diagnostic markers associated with INRs through bioinformatic analyses of public datasets. Methods: This study retrieved the microarray data sets of GSE106792 and GSE77939 from the Gene Expression Omnibus (GEO) database. After merging two microarray data and adjusting the batch effect, differentially expressed genes (DEGs) were identified. Gene Ontology (GO) resource and Kyoto Encyclopedia of Genes and Genomes (KEGG) resource were conducted to analyze the biological process and functional enrichment. We performed receiver operating characteristic (ROC) curves to filtrate potential diagnostic markers for INRs. Gene Set Enrichment Analysis (GSEA) was conducted to perform the pathway enrichment analysis of individual genes. Single sample GSEA (ssGSEA) was performed to assess scores of immune cells within INRs and IRs. The correlations between the diagnostic markers and differential immune cells were examined by conducting Spearman's rank correlation analysis. Subsequently, miRNA-mRNA-TF interaction networks in accordance with the potential diagnostic markers were built with Cytoscape. We finally verified the mRNA expression of the diagnostic markers in clinical samples of INRs and IRs by performing RT-qPCR. Results: We identified 52 DEGs in the samples of peripheral blood mononuclear cells (PBMC) between INRs and IRs. A few inflammatory and immune-related pathways, including chronic inflammatory response, T cell receptor signaling pathway, were enriched. FAM120AOS, LTA, FAM179B, JUN, PTMA, and SH3YL1 were considered as potential diagnostic markers. ssGSEA results showed that the IRs had significantly higher enrichment scores of seven immune cells compared with IRs. The miRNA-mRNA-TF network was constructed with 97 miRNAs, 6 diagnostic markers, and 26 TFs, which implied a possible regulatory relationship. Conclusion: The six potential crucial genes, FAM120AOS, LTA, FAM179B, JUN, PTMA, and SH3YL1, may be associated with clinical diagnosis in INRs. Our study provided new insights into diagnostic and therapeutic targets.", "claims": [{"id": "claim-method", "statement": "The DEGs were determined between INRs and IRs samples with the “limma” R package (Ritchie et al., 2015; Phipson et al., 2016).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35004856", "locator": "sections[5] \"Identification of Differentially Expressed Genes\" paragraph 2", "quote": "The DEGs were determined between INRs and IRs samples with the “limma” R package (Ritchie et al., 2015; Phipson et al., 2016)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35004856", "locator": "sections[21] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "ROC analysis identified six genes—FAM120AOS, LTA, FAM179B, JUN, PTMA, and SH3YL1—with AUC values greater than 0.9 as potential diagnostic markers distinguishing INRs from IRs.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35004856", "locator": "sections[15] \"Identification of the Diagnostic Markers and Gene Set Enrichment Analysis\" paragraph 2", "quote": "ROC analysis was conducted on the 52 DEGs and excavated six genes (FAM120AOS, LTA, FAM179B, JUN, PTMA, SH3YL1) with AUC values over 0.9 (Figures 3A–F), thereby illustrating that the mentioned genes exhibited a powerful discrimination ability to discriminate INRs samples from the IRs samples."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "ROC analysis identified six genes—FAM120AOS, LTA, FAM179B, JUN, PTMA, and SH3YL1—with AUC values greater than 0.9 as potential diagnostic markers distinguishing INRs from IRs.", "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:35004856"], "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:GSE106792"], "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:GSE106792"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35004856", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fmolb.2021.809085", "sha256": "sha256:baa71b89ba0cbcae6a4572038da303d4a71ec2777a2c93a02d60a8743ec33036", "bytes": 32198, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fmolb.2021.809085", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8727996", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE106792", "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=GSE106792", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE106792", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2850330", "GSM2850331", "GSM2850332", "GSM2850333", "GSM2850334", "GSM2850335", "GSM2850336", "GSM2850337", "GSM2850338", "GSM2850339", "GSM2850340", "GSM2850341", "GSM2850342", "GSM2850343", "GSM2850344", "GSM2850345", "GSM2850346", "GSM2850347", "GSM2850348", "GSM2850349", "GSM2850350", "GSM2850351", "GSM2850352", "GSM2850353", "GSM2850354", "GSM2850355", "GSM2850356", "GSM2850357", "GSM2850358", "GSM2850359", "GSM2850360", "GSM2850361", "GSM2850362", "GSM2850363", "GSM2850364", "GSM2850365"], "sample_count": 36, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "Cycling CD4+  T cells in HIV-infected immune nonresponders have mitochondrial dysfunction", "resolution_checked_at": "2026-11-01T17:30:42Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE77939", "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=GSE77939", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE77939", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2061728", "GSM2061729", "GSM2061730", "GSM2061731", "GSM2061732", "GSM2061733", "GSM2061734", "GSM2061735", "GSM2061736", "GSM2061737", "GSM2061738", "GSM2061739", "GSM2061740", "GSM2061741", "GSM2061742", "GSM2061743", "GSM2061744", "GSM2061745", "GSM2061746", "GSM2061747", "GSM2061748"], "sample_count": 21, "group_sizes": null, "group_sizes_basis": null, "platform": "15207", "taxon": "Homo sapiens", "title": "Gene expression data from immunological non-responders and responders to antiretroviral therapy in HIV infected patients", "resolution_checked_at": "2026-11-01T17:30:42Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE106792 not downloaded", "asset:data:geo:GSE106792 licence not read", "asset:data:geo:GSE77939 not downloaded", "asset:data:geo:GSE77939 licence not read"]}, "analysis": {"state": "complete", "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": "The DEGs were determined between INRs and IRs samples with the “limma” R package (Ritchie et al., 2015; Phipson et al., 2016)."}}, {"id": "method-2", "family": "correlation_analysis", "specific": "spearman", "label": "Correlation analysis", "dsl_operations": ["spearman_rho"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.7, "band": "medium", "quote": "Spearman's rank correlation"}}, {"id": "method-3", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "pathway enrichment"}}], "targets": [], "gaps": []}, "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": ["GSE106792", "GSE77939"], "resolved_accessions": ["GSE106792", "GSE77939"], "statements": ["The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author."], "basis": "The paper names GSE106792, GSE77939 in NCBI GEO database 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:35004856", "data:geo:GSE106792"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE106792"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:15:16Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 9745, "completion_tokens": 1421, "cached_tokens": 128}}, "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:35004856", "type": "paper", "label": "pmid:35004856"}, {"id": "source:pmid:35004856", "type": "manuscript", "label": "PMID 35004856 full text"}, {"id": "data:geo:GSE106792", "type": "dataset", "label": "GEO GSE106792"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35004856", "type": "paper", "label": "pmid:35004856"}, {"id": "source:pmid:35004856", "type": "manuscript", "label": "PMID 35004856 full text"}, {"id": "data:geo:GSE106792", "type": "dataset", "label": "GEO GSE106792"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35004856", "type": "extraction", "used": ["source:pmid:35004856"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE106792", "type": "accession_resolution", "used": ["data:geo:GSE106792"], "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:35004856", "parent_hash": "sha256:1a3238b05532f67724906016b007add2b19e34b3a2d7a2fcf07f73d9de4d4879", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE106792 licence not read", "asset:data:geo:GSE106792 not downloaded", "asset:data:geo:GSE77939 licence not read", "asset:data:geo:GSE77939 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["inical samples of INRs and IRs by performing RT-qPCR. Results: We identified 52 DEGs in the sampl", "cal samples of INRs and IRs by performing RT-qPCR. Results: We identified 52 DEGs in the sampl"], "order_basis": "paper_text_order:1709", "id": "assay:1"}, {"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": ["The DEGs were determined between INRs and IRs samples with the “limma” R package (Ritchie et al., 2015; Phipson et al., 2016)."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}