← All .science files
pmid:41097329
Exometabolome and Molecular Signatures Associated with HPV 16 in Cervical Cancer: Integrative Metabolomic and Transcriptomic Analysis for Biomarker Discovery.
Adán Arizmendi-Izazaga · Napoleón Navarro-Tito · Gabriela Elizabeth Campos-Viguri · Hilda Jiménez-Wences · Macdiel Emilio Acevedo-Quiroz · Eric Genaro Salmerón-Bárcenas · Berenice Illades-Aguiar · Marco Antonio Leyva-Vázquez · Julio Ortiz-Ortiz
Molecules (Basel, Switzerland) · 2025 doi:10.3390/molecules30193909
Paper
complete
Experiment
partial
Data
partial
Analysis
partial
Execution
absent
Execution evidence has not yet been added to this .science file. Explore its methods, data and open questions to plan the next step.
Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
paper object · 10 fields
authors array · 9 items
claims array · 3 items
[0] object · 6 fields
evidence array · 1 item
[0] object · 3 fields
[1] object · 6 fields
[2] object · 6 fields
gaps array · 0 items
experiment object · 8 fields
steps array · 3 items
[0] object · 13 fields
parameters object · 0 fields
inputs array · 1 item
outputs array · 1 item
instruments array · 0 items
reagents array · 0 items
[1] object · 13 fields
parameters object · 0 fields
inputs array · 1 item
outputs array · 1 item
instruments array · 0 items
reagents array · 0 items
[2] object · 13 fields
parameters object · 0 fields
inputs array · 1 item
outputs array · 1 item
instruments array · 0 items
reagents array · 0 items
materials array · 0 items
instruments array · 0 items
reagents array · 0 items
conditions object · 0 fields
gaps array · 1 item
data object · 3 fields
assets array · 2 items
[0] object · 15 fields
structure object · 4 fields
[1] object · 15 fields
structure object · 15 fields
sample_accessions array · 66 items
gaps array · 2 items
analysis object · 4 fields
methods array · 2 items
[0] object · 10 fields
dsl_operations array · 0 items
missing_operations array · 1 item
parameters object · 0 fields
data_shapes array · 1 item
evidence object · 3 fields
[1] object · 10 fields
dsl_operations array · 1 item
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
targets array · 0 items
gaps array · 2 items
capability object · 3 fields
requirements array · 1 item
[0] object · 6 fields
assay_families array · 9 items
gaps array · 0 items
readiness object · 8 fields
axes object · 3 fields
method object · 5 fields
required_operations array · 0 items
missing_operations array · 1 item
capability object · 4 fields
data object · 6 fields
accessions array · 1 item
resolved_accessions array · 1 item
statements array · 1 item
can_run object · 3 fields
dsl_operations array · 0 items
assets array · 2 items
steps array · 0 items
must_build object · 5 fields
dsl_operations array · 1 item
[0] object · 3 fields
converters array · 0 items
readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
gaps array · 0 items
review object · 5 fields
machine_critique object · 5 fields
reader object · 5 fields
evidence_check object · 2 fields
usage object · 3 fields
stages array · 1 item
[0] object · 4 fields
gaps array · 3 items
provenance object · 7 fields
entities array · 3 items
activities array · 3 items
[0] object · 4 fields
used array · 3 items
[0] object · 3 fields
[1] object · 3 fields
[2] object · 3 fields
[1] object · 4 fields
agents array · 2 items
lineage object · 4 fields
gaps array · 9 items
assays array · 2 items
[0] object · 11 fields
required_operations array · 0 items
source_hashes object · 1 field
evidence array · 2 items
[1] object · 11 fields
required_operations array · 0 items
source_hashes object · 1 field
evidence array · 1 item
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41097329", "kind": "science-record", "revision": 4, "content_hash": "sha256:95756751cacf52f3e9104af20aa956a86e8a47bee78c0668fa27985f7452c088", "created_at": "2026-11-01T20:31:09Z", "updated_at": "2026-11-01T22:57:19Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Exometabolome and Molecular Signatures Associated with HPV 16 in Cervical Cancer: Integrative Metabolomic and Transcriptomic Analysis for Biomarker Discovery.", "doi": "10.3390/molecules30193909", "pmid": "41097329", "authors": ["Adán Arizmendi-Izazaga", "Napoleón Navarro-Tito", "Gabriela Elizabeth Campos-Viguri", "Hilda Jiménez-Wences", "Macdiel Emilio Acevedo-Quiroz", "Eric Genaro Salmerón-Bárcenas", "Berenice Illades-Aguiar", "Marco Antonio Leyva-Vázquez", "Julio Ortiz-Ortiz"], "journal": "Molecules (Basel, Switzerland)", "year": 2025, "abstract": "Cervical cancer (CC) represents a major public health concern, ranking as the fourth most frequently diagnosed cancer and one of the leading causes of cancer-related mortality among middle-aged women worldwide. CC is caused by persistent infection with high-risk human papillomaviruses (HR-HPVs), with HPV 16 being the cause of more than 50% of CC cases. In this study, the exometabolome of the HPV 16-positive cell lines SiHa and Ca Ski, as well as the HPV 16-negative control cell line C-33 A, was evaluated. The exometabolome was validated through molecular signatures using a transcriptomic approach to identify genes encoding cellular metabolic enzymes. The exometabolome was analyzed using 1H nuclear magnetic resonance spectroscopy (1H-NMR). Exometabolomic profiles were subsequently compared through both multivariate and univariate statistical analyses to identify significant differences between cell lines. Molecular signatures were analyzed from the GSE9750 dataset obtained from the GEO database. Exometabolic profiling of the HPV 16 positive cell lines showed higher concentrations of leucine, isoleucine, valine, lysine, methionine, glutamine, ornithine, choline, glucose, and tryptophan. An expression analysis showed increased expression of enzymes involved in amino acid synthesis, the tricarboxylic acid cycle, glycolysis, the pentose phosphate pathway, galactose metabolism, and HIF-1α. These data suggest metabolites and metabolism-associated genes that can be used as non-invasive, stable diagnostic and prognostic biomarkers, as well as therapeutic targets for CC in the presence of HPV 16.", "claims": [{"id": "claim-method", "statement": "PCA was used to examine intrinsic variability within the dataset, to observe clustering or separation trends, and to identify outliers. OPLS-DA was applied to minimize the potential contribution of intergroup variability and to improve the separation between sample groups further.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41097329", "locator": "sections[12] \"4.4. Multivariate Analysis\" paragraph 3", "quote": "PCA was used to examine intrinsic variability within the dataset, to observe clustering or separation trends, and to identify outliers. OPLS-DA was applied to minimize the potential contribution of intergroup variability and to improve the separation between sample groups further."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The links to the expression data were posted in the Section 4.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41097329", "locator": "sections[23] \"Data Availability Statement\" paragraph 2", "quote": "The links to the expression data were posted in the Section 4."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Exometabolic profiling of the HPV 16 positive cell lines showed higher concentrations of leucine, isoleucine, valine, lysine, methionine, glutamine, ornithine, choline, glucose, and tryptophan.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41097329", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Exometabolic profiling of the HPV 16 positive cell lines showed higher concentrations of leucine, isoleucine, valine, lysine, methionine, glutamine, ornithine, choline, glucose, and tryptophan."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Exometabolic profiling of the HPV 16 positive cell lines showed higher concentrations of leucine, isoleucine, valine, lysine, methionine, glutamine, ornithine, choline, glucose, and tryptophan.", "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:41097329"], "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:GSE9750"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:student_t", "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:GSE9750"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:student_t"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41097329", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/molecules30193909", "sha256": "sha256:6cda5c933402d129ad6a5609d556c0d06617c678a885a2dc3161cb0b58fd3d21", "bytes": 64041, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3390/molecules30193909", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12525624", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE9750", "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=GSE9750", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE9750", "version": null, "note": "The links to the expression data were posted in the Section 4.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The links to the expression data were posted in the Section 4.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM246087", "GSM246088", "GSM246089", "GSM246090", "GSM246119", "GSM246120", "GSM246121", "GSM246122", "GSM246123", "GSM246422", "GSM246423", "GSM246484", "GSM246485", "GSM246486", "GSM246487", "GSM246488", "GSM246489", "GSM246490", "GSM246491", "GSM247162", "GSM247163", "GSM247164", "GSM247165", "GSM247166", "GSM247168", "GSM247169", "GSM247171", "GSM247173", "GSM247174", "GSM247175", "GSM247188", "GSM247189", "GSM247190", "GSM247650", "GSM247651", "GSM247652", "GSM247653", "GSM247654", "GSM247655", "GSM247656", "GSM247657", "GSM247658", "GSM247659", "GSM247660", "GSM247661", "GSM247662", "GSM247663", "GSM247856", "GSM247857", "GSM247859", "GSM247860", "GSM247862", "GSM247864", "GSM247865", "GSM247866", "GSM247876", "GSM247877", "GSM247878", "GSM247879", "GSM247881", "GSM247882", "GSM247883", "GSM247884", "GSM247885", "GSM247886", "GSM247887"], "sample_count": 66, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Identification of gene expression profiles in cervical cancer ", "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:GSE9750 not downloaded", "asset:data:geo:GSE9750 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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": 1.0, "band": "verbatim", "quote": "PCA was used to examine intrinsic variability within the dataset, to observe clustering or separation trends, and to identify outliers. OPLS-DA was applied to minimize the potential contribution of intergroup variability and to improve the separation between sample groups further."}}, {"id": "method-2", "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": "Principal Component Analysis"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor", "method.student_t"]}, "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": false, "required_operations": [], "missing_operations": ["student_t"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: student_t_test."}, "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": ["GSE9750"], "resolved_accessions": ["GSE9750"], "statements": ["The links to the expression data were posted in the Section 4."], "basis": "The paper names GSE9750 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": [], "assets": ["source:pmid:41097329", "data:geo:GSE9750"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "student_t", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE9750"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T20:03:12Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 18817, "completion_tokens": 1751, "cached_tokens": 264}}, "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:41097329", "type": "paper", "label": "pmid:41097329"}, {"id": "source:pmid:41097329", "type": "manuscript", "label": "PMID 41097329 full text"}, {"id": "data:geo:GSE9750", "type": "dataset", "label": "GEO GSE9750"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:41097329", "type": "paper", "label": "pmid:41097329"}, {"id": "source:pmid:41097329", "type": "manuscript", "label": "PMID 41097329 full text"}, {"id": "data:geo:GSE9750", "type": "dataset", "label": "GEO GSE9750"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-41097329", "type": "extraction", "used": ["source:pmid:41097329"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE9750", "type": "accession_resolution", "used": ["data:geo:GSE9750"], "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:41097329", "parent_hash": "sha256:a0edc0ed6d1fae13ad1ca42f80251f95909de7b8a4b195c08ebe19a06dc78269", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE9750 licence not read", "asset:data:geo:GSE9750 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "method.student_t", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:student_t"], "assays": [{"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["metabolomic profiles of the media where the cell lines were cultured. Assignment of metabolites in a typical H-CP", "genome) were acquired from the ATCC and were cultured in DMEM (Dulbecco’s modified Eagle’s medium) su"], "order_basis": "paper_text_order:2585", "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": 1.0, "evidence": ["PCA was used to examine intrinsic variability within the dataset, to observe clustering or separation trends, and to identify outliers. OPLS-DA was applied to minimize the potential contribution of intergroup variability and to improve the separation between sample groups further."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}