Topoisomerase I inhibition leads to length-dependent gene expression changes in human primary astrocytes.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:28119819", "kind": "science-record", "revision": 6, "content_hash": "sha256:64694416903e0748419c298cb7223c737eabb27ba241e79ec55685dd6fe4f012", "created_at": "2026-11-01T15:40:22Z", "updated_at": "2026-11-01T21:20:47Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Topoisomerase I inhibition leads to length-dependent gene expression changes in human primary astrocytes.", "doi": "10.1016/j.gdata.2016.12.005", "pmid": "28119819", "authors": ["Akira Gokoolparsadh", "Zhiming Fang", "Nady Braidy", "Irina Voineagu"], "journal": "Genomics data", "year": 2017, "abstract": "Topoisomerase I is required for the proper expression of long genes (> 100 kb) in mouse and human cortical neurons, including many candidate genes for autism spectrum disorder (ASD) [1]. Given the important role of astrocytes in brain development [2], we investigated whether long genes, including autism susceptibility genes, also require topoisomerase I expression in human primary astrocytes. We carried genome-wide expression profiling of cultured human primary astrocytes following treatment with the topoisomerase I inhibitor Topotecan, using Illumina microarrays. We identified several thousands of differentially expressed genes and confirmed that topoisomerase I inhibition affects gene expression in human primary astrocytes in a length-dependent manner. We also identified over 20 ASD-associated genes that show topoisomerase-dependent gene expression in human primary astrocytes but have not been previously reported as topoisomerase-I-dependent in neurons. The microarray data have been deposited in NCBI GEO (https://www.ncbi.nlm.nih.gov/geo/) under accession number GSE90052.", "claims": [{"id": "claim-method", "statement": "We observed a significant inverse correlation between gene length and expression change at both time points (Fig. 1; Spearman rho = − 0.57, p value = 4.73 E-252 at 24 h; Spearman rho = − 0.38, p value = 2.85 E-97 at 48 h).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28119819", "locator": "sections[9] \"Results and discussion\" paragraph 2", "quote": "We observed a significant inverse correlation between gene length and expression change at both time points (Fig. 1; Spearman rho = − 0.57, p value = 4.73 E-252 at 24 h; Spearman rho = − 0.38, p value = 2.85 E-97 at 48 h)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The microarray data have been deposited in NCBI GEO (https://www.ncbi.nlm.nih.gov/geo/) under accession number GSE90052.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28119819", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The microarray data have been deposited in NCBI GEO (https://www.ncbi.nlm.nih.gov/geo/) under accession number GSE90052."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Topoisomerase I inhibition produced length-dependent gene-expression changes in human primary astrocytes, with a significant inverse correlation between gene length and expression change at both 24 h (Spearman rho = − 0.57, p value = 4.73 E-252) and 48 h (Spearman rho = − 0.38, p value = 2.85 E-97); the source microarray data are available from NCBI GEO under accession GSE90052.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:28119819", "locator": "sections[9] \"Results and discussion\" paragraph 2", "quote": "We observed a significant inverse correlation between gene length and expression change at both time points (Fig. 1; Spearman rho = − 0.57, p value = 4.73 E-252 at 24 h; Spearman rho = − 0.38, p value = 2.85 E-97 at 48 h)."}, {"asset": "source:pmid:28119819", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The microarray data have been deposited in NCBI GEO (https://www.ncbi.nlm.nih.gov/geo/) under accession number GSE90052."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Topoisomerase I inhibition produced length-dependent gene-expression changes in human primary astrocytes, with a significant inverse correlation between gene length and expression change at both 24 h (Spearman rho = − 0.57, p value = 4.73 E-252) and 48 h (Spearman rho = − 0.38, p value = 2.85 E-97); the source microarray data are available from NCBI GEO under accession GSE90052.", "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:28119819"], "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:GSE90052"], "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:GSE90052"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:28119819", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.gdata.2016.12.005", "sha256": "sha256:578c1af996de42d2c62228f9e4fa2a80b99f74b91066bfc42a548fda35e2060d", "bytes": 10750, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.gdata.2016.12.005", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC5238604", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE90052", "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=GSE90052", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE90052", "version": null, "note": "The microarray data have been deposited in NCBI GEO (https://www.ncbi.nlm.nih.gov/geo/) under accession number GSE90052.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The microarray data have been deposited in NCBI GEO (https://www.ncbi.nlm.nih.gov/geo/) under accession number GSE90052.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2396563", "GSM2396564", "GSM2396565", "GSM2396566", "GSM2396567", "GSM2396568", "GSM2396569", "GSM2396570", "GSM2396571", "GSM2396572", "GSM2396573", "GSM2396574"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "Topoisomerase I dependent gene expression in human primary astrocytes", "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:28119819:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:0d9bc127d5b2f2bb313dae058ea6ae9b50bba6d0bc4bf0de557813b257c4b86c", "bytes": 646, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[1]/table-wrap[1]#t0010", "version": null, "note": null, "structure": {"pmcid": "PMC5238604", "section_index": 1, "section_title": "Specifications [standardized info for the reader]", "row_count": 8, "column_count": 2}, "table": {"label": null, "caption": null, "rows": [["Organism/cell line/tissue", "Homo sapiens/primary astrocytes isolated from 14–18-week-old postmortem fetal brain"], ["Sex", "NA"], ["Sequencer or array type", "Illumina HumanHT-12 v4"], ["Data format", "Raw and normalized"], ["Experimental factors", "Topoisomerase I inhibition"], ["Experimental features", "Triplicate cultures of human primary astrocytes were treated with 300 nM Topotecan or 0.1% DMSO (as control), for either 24 or 48 h."], ["Consent", "NA"], ["Sample source location", "Sydney, Australia"]], "row_count": 8, "column_count": 2, "numeric_cells": 3, "header_rows": 0, "locator": "section[1]/table-wrap[1]#t0010"}}, {"id": "asset:table:pmid:28119819:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:925a3ff97e119ec041272eead6fe965748968c5fc9dc6ea3257848ecd4fa09ee", "bytes": 2795, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[9]/table-wrap[1]#t0005", "version": null, "note": "ASD genes differentially expressed upon topotecan treatment. ProbeID: Illumina Array Address ID. P value: Differential expression p-value at the corresponding time point, after multiple testing correction.", "structure": {"pmcid": "PMC5238604", "section_index": 9, "section_title": "Results and discussion", "row_count": 43, "column_count": 6}, "table": {"label": "Table 1", "caption": "ASD genes differentially expressed upon topotecan treatment. ProbeID: Illumina Array Address ID. P value: Differential expression p-value at the corresponding time point, after multiple testing correction.", "rows": [["Gene symbol", "ProbeID", "log2 fold change", "p value", "Gene length (bp)", "Time point"], ["ADSL", "5870228", "− 0.67", "1.13E-04", "20249", "48 h"], ["ADSL", "5870228", "− 0.64", "2.67E-03", "20249", "24 h"], ["AHI1", "5860253", "0.65", "2.10E-03", "213794", "24 h"], ["AHI1", "5860253", "0.96", "6.40E-06", "213794", "48 h"], ["ANKRD11", "3370274", "− 0.77", "1.81E-02", "222941", "24 h"], ["BCKDK", "5220347", "− 0.59", "3.65E-04", "4498", "48 h"], ["CTNND2", "4610075", "− 1.36", "5.94E-03", "932203", "24 h"], ["CTNND2", "4610075", "− 0.93", "9.41E-06", "932203", "48 h"], ["DHCR7", "5360678", "− 0.80", "4.85E-05", "14021", "48 h"], ["DHCR7", "6550048", "− 0.69", "1.21E-04", "14021", "48 h"], ["DMPK", "3930164", "0.90", "4.77E-05", "12849", "48 h"], ["EP300", "7570068", "0.66", "8.78E-05", "87468", "48 h"], ["HDAC4", "5900468", "− 1.13", "4.70E-04", "352782", "24 h"], ["HDAC4", "5900468", "− 0.79", "6.98E-05", "352782", "48 h"], ["HERC2", "6130674", "− 0.87", "7.44E-03", "211116", "24 h"], ["KAT2B", "7200703", "− 0.92", "2.31E-03", "114373", "24 h"], ["NFIX", "5720129", "− 0.60", "4.00E-03", "103027", "24 h"], ["NTNG1", "6940053", "− 1.45", "5.23E-07", "344982", "48 h"], ["NTNG1", "4390333", "− 1.19", "6.10E-07", "344982", "48 h"], ["OCRL", "60324", "0.66", "7.83E-05", "52279", "48 h"], ["PRKD1", "1070184", "− 0.78", "3.66E-03", "351213", "24 h"], ["RAI1", "520561", "− 0.73", "2.26E-03", "129979", "24 h"], ["RPS6KA3", "3370110", "− 0.62", "9.64E-05", "116722", "48 h"], ["SGSH", "1340538", "0.87", "1.18E-02", "11121", "24 h"], ["SGSH", "1340538", "0.94", "2.89E-05", "11121", "48 h"], ["SNX14", "4260504", "− 0.74", "1.37E-03", "88660", "24 h"], ["SNX14", "1990561", "− 0.63", "4.83E-03", "88660", "24 h"], ["STXBP1", "6100112", "0.62", "1.76E-04", "80510", "48 h"], ["STXBP1", "1260564", "0.84", "2.45E-05", "80510", "48 h"], ["TCF4", "2510672", "− 1.26", "1.23E-06", "366299", "48 h"], ["TCF4", "2510672", "− 1.14", "9.25E-04", "366299", "24 h"], ["TSC2", "450376", "− 0.60", "6.78E-03", "40826", "24 h"], ["UBE3A", "2360379", "− 0.94", "1.65E-03", "101780", "24 h"], ["UBE3A", "1990307", "− 0.93", "1.38E-03", "101780", "24 h"], ["UPF3B", "780743", "1.19", "1.87E-06", "19003", "48 h"], ["UPF3B", "4640239", "1.21", "1.63E-06", "19003", "48 h"], ["UPF3B", "780743", "1.38", "2.40E-04", "19003", "24 h"], ["UPF3B", "4640239", "1.43", "1.24E-04", "19003", "24 h"], ["USP7", "4640670", "− 0.70", "1.79E-03", "71391", "24 h"], ["USP7", "4640670", "− 0.60", "1.42E-04", "71391", "48 h"], ["ZBTB20", "3440189", "− 0.73", "2.26E-03", "832781", "24 h"], ["ZBTB20", "3440189", "− 0.64", "1.57E-04", "832781", "48 h"]], "row_count": 43, "column_count": 6, "numeric_cells": 216, "header_rows": 1, "locator": "section[9]/table-wrap[1]#t0005"}}], "gaps": ["asset:data:geo:GSE90052 not downloaded", "asset:data:geo:GSE90052 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "correlation_analysis", "specific": "spearman", "label": "Correlation analysis", "dsl_operations": ["spearman_rho"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "We observed a significant inverse correlation between gene length and expression change at both time points (Fig. 1; Spearman rho = − 0.57, p value = 4.73 E-252 at 24 h; Spearman rho = − 0.38, p value = 2.85 E-97 at 48 h)."}}], "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": ["spearman_rho"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: spearman."}, "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": ["GSE90052"], "resolved_accessions": ["GSE90052"], "statements": ["The microarray data have been deposited in NCBI GEO (https://www.ncbi.nlm.nih.gov/geo/) under accession number GSE90052."], "basis": "The paper names GSE90052 in NCBI GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["spearman_rho"], "assets": ["source:pmid:28119819", "data:geo:GSE90052", "asset:table:pmid:28119819:1", "asset:table:pmid:28119819:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE90052"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:30:23Z", "independence": "same_provider"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 8, "usage": {"prompt_tokens": 26805, "completion_tokens": 3192, "cached_tokens": 4640}}, "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:28119819", "type": "paper", "label": "pmid:28119819"}, {"id": "source:pmid:28119819", "type": "manuscript", "label": "PMID 28119819 full text"}, {"id": "data:geo:GSE90052", "type": "dataset", "label": "GEO GSE90052"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:28119819", "type": "paper", "label": "pmid:28119819"}, {"id": "source:pmid:28119819", "type": "manuscript", "label": "PMID 28119819 full text"}, {"id": "data:geo:GSE90052", "type": "dataset", "label": "GEO GSE90052"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-28119819", "type": "extraction", "used": ["source:pmid:28119819"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE90052", "type": "accession_resolution", "used": ["data:geo:GSE90052"], "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:28119819", "parent_hash": "sha256:6adc7179763c73e60082dffbd8244aa08837f2575635e498d9736cd8ed91410e", "fork_of": null, "generation": 5}, "gaps": ["asset:data:geo:GSE90052 licence not read", "asset:data:geo:GSE90052 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["roper expression of long genes (> 100 kb) in mouse and human cortical neurons, including many c"], "order_basis": "paper_text_order:143", "id": "assay:1"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["as topoisomerase-I-dependent in neurons. The microarray data have been deposited in NCBI GEO (https:"], "order_basis": "paper_text_order:1035", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["out as previously described [13]. Cells were cultured in RPMI 1640 medium (Life Technologies, no. 618"], "order_basis": "paper_text_order:1464", "id": "assay:3"}, {"role": "analysis", "definition_id": "correlation_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["spearman_rho"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["We observed a significant inverse correlation between gene length and expression change at both time points (Fig. 1; Spearman rho = − 0.57, p value = 4.73 E-252 at 24 h; Spearman rho = − 0.38, p value = 2.85 E-97 at 48 h)."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}