Inter-species pathway perturbation prediction via data-driven detection of functional homology.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:25150249", "kind": "science-record", "revision": 2, "content_hash": "sha256:0aa629bb730a5de408d8d8baa2b1784af788ccbb5a4e25908a36228166ad373b", "created_at": "2026-11-01T15:40:05Z", "updated_at": "2026-11-01T18:47:09Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Inter-species pathway perturbation prediction via data-driven detection of functional homology.", "doi": "10.1093/bioinformatics/btu570", "pmid": "25150249", "authors": ["Christoph Hafemeister", "Roberto Romero", "Erhan Bilal", "Pablo Meyer", "Raquel Norel", "Kahn Rhrissorrakrai", "Richard Bonneau", "Adi L Tarca"], "journal": "Bioinformatics (Oxford, England)", "year": 2015, "abstract": "MOTIVATION: Experiments in animal models are often conducted to infer how humans will respond to stimuli by assuming that the same biological pathways will be affected in both organisms. The limitations of this assumption were tested in the IMPROVER Species Translation Challenge, where 52 stimuli were applied to both human and rat cells and perturbed pathways were identified. In the Inter-species Pathway Perturbation Prediction sub-challenge, multiple teams proposed methods to use rat transcription data from 26 stimuli to predict human gene set and pathway activity under the same perturbations. Submissions were evaluated using three performance metrics on data from the remaining 26 stimuli.\nRESULTS: We present two approaches, ranked second in this challenge, that do not rely on sequence-based orthology between rat and human genes to translate pathway perturbation state but instead identify transcriptional response orthologs across a set of training conditions. The translation from rat to human accomplished by these so-called direct methods is not dependent on the particular analysis method used to identify perturbed gene sets. In contrast, machine learning-based methods require performing a pathway analysis initially and then mapping the pathway activity between organisms. Unlike most machine learning approaches, direct methods can be used to predict the activation of a human pathway for a new (test) stimuli, even when that pathway was never activated by a training stimuli.\nAVAILABILITY: Gene expression data are available from ArrayExpress (accession E-MTAB-2091), while software implementations are available from http://bioinformaticsprb.med.wayne.edu?p=50 and http://goo.gl/hJny3h.\nCONTACT: christoph.hafemeister@nyu.edu or atarca@med.wayne.edu.\nSUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.", "claims": [{"id": "claim-target-result", "statement": "The paper used two direct, non-sequence-based translation approaches that identify transcriptional response orthologs across training conditions to predict human pathway perturbation states from rat transcription data; the source gene-expression data are available through ArrayExpress under accession E-MTAB-2091.", "kind": "quantitative", "target": {"value": 50.0, "unit": "p-value", "tolerance": null, "source": "Gene expression data are available from ArrayExpress (accession E-MTAB-2091), while software implementations are available from http://bioinformaticsprb.med.wayne.edu?p=50 and http://goo.gl/hJny3h."}, "evidence": [{"asset": "source:pmid:25150249", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "We present two approaches, ranked second in this challenge, that do not rely on sequence-based orthology between rat and human genes to translate pathway perturbation state but instead identify transcriptional response orthologs across a set of training conditions."}, {"asset": "source:pmid:25150249", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Gene expression data are available from ArrayExpress (accession E-MTAB-2091), while software implementations are available from http://bioinformaticsprb.med.wayne.edu?p=50 and http://goo.gl/hJny3h."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The paper used two direct, non-sequence-based translation approaches that identify transcriptional response orthologs across training conditions to predict human pathway perturbation states from rat transcription data; the source gene-expression data are available through ArrayExpress under accession E-MTAB-2091.", "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:25150249"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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