Exploiting the full power of temporal gene expression profiling through a new statistical test: application to the analysis of muscular dystrophy data.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:16584545", "kind": "science-record", "revision": 6, "content_hash": "sha256:5593c63cd33bf8c78e0eaf17f88da1c1fe5b1c3411c33c2c7d1ab25c820764c3", "created_at": "2026-11-01T15:40:00Z", "updated_at": "2026-11-01T21:19:34Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Exploiting the full power of temporal gene expression profiling through a new statistical test: application to the analysis of muscular dystrophy data.", "doi": "10.1186/1471-2105-7-183", "pmid": "16584545", "authors": ["Veronica Vinciotti", "Xiaohui Liu", "Rolf Turk", "Emile J de Meijer", "Peter A C 't Hoen"], "journal": "BMC bioinformatics", "year": 2006, "abstract": "BACKGROUND: The identification of biologically interesting genes in a temporal expression profiling dataset is challenging and complicated by high levels of experimental noise. Most statistical methods used in the literature do not fully exploit the temporal ordering in the dataset and are not suited to the case where temporal profiles are measured for a number of different biological conditions. We present a statistical test that makes explicit use of the temporal order in the data by fitting polynomial functions to the temporal profile of each gene and for each biological condition. A Hotelling T2-statistic is derived to detect the genes for which the parameters of these polynomials are significantly different from each other.\nRESULTS: We validate the temporal Hotelling T2-test on muscular gene expression data from four mouse strains which were profiled at different ages: dystrophin-, beta-sarcoglycan and gamma-sarcoglycan deficient mice, and wild-type mice. The first three are animal models for different muscular dystrophies. Extensive biological validation shows that the method is capable of finding genes with temporal profiles significantly different across the four strains, as well as identifying potential biomarkers for each form of the disease. The added value of the temporal test compared to an identical test which does not make use of temporal ordering is demonstrated via a simulation study, and through confirmation of the expression profiles from selected genes by quantitative PCR experiments. The proposed method maximises the detection of the biologically interesting genes, whilst minimising false detections.\nCONCLUSION: The temporal Hotelling T2-test is capable of finding relatively small and robust sets of genes that display different temporal profiles between the conditions of interest. The test is simple, it can be used on gene expression data generated from any experimental design and for any number of conditions, and it allows fast interpretation of the temporal behaviour of genes. The R code is available from V.V. The microarray data have been submitted to GEO under series GSE1574 and GSE3523.", "claims": [{"id": "claim-method", "statement": "We have applied the temporal Hotelling T2-test with second order polynomials on microarray data from wild-type mice and three mouse strains with different forms of muscular dystrophy, to identify genes with differences in temporal expression profiles between the four strains.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:16584545", "locator": "sections[7] \"Analysis of muscular dystrophy dataset\" paragraph 2", "quote": "We have applied the temporal Hotelling T2-test with second order polynomials on microarray data from wild-type mice and three mouse strains with different forms of muscular dystrophy, to identify genes with differences in temporal expression profiles between the four strains."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The microarray data have been submitted to GEO under series GSE1574 and GSE3523.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:16584545", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The microarray data have been submitted to GEO under series GSE1574 and GSE3523."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The paper presents the temporal Hotelling T2-test, a polynomial-based statistical test for detecting genes with significantly different temporal profiles across biological conditions, and identifies the source microarray data through GEO series GSE1574 and GSE3523.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:16584545", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We present a statistical test that makes explicit use of the temporal order in the data by fitting polynomial functions to the temporal profile of each gene and for each biological condition. A Hotelling T2-statistic is derived to detect the genes for which the parameters of these polynomials are significantly different from each other."}, {"asset": "source:pmid:16584545", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The microarray data have been submitted to GEO under series GSE1574 and GSE3523."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The paper presents the temporal Hotelling T2-test, a polynomial-based statistical test for detecting genes with significantly different temporal profiles across biological conditions, and identifies the source microarray data through GEO series GSE1574 and GSE3523.", "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:16584545"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": [], "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": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:16584545", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/1471-2105-7-183", "sha256": "sha256:011aae0dbbbbc5e22fcc59c4e0f29fd559677363128df7f30c601dc035594ea3", "bytes": 55968, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/1471-2105-7-183", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC1450310", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "asset:table:pmid:16584545:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ddeaa23015f7a5043f0cfabf554a98bbdda683673535abc4ddcbb5d7d8533757", "bytes": 2933, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[7]/table-wrap[1]#T1", "version": null, "note": "Biomarker genes for the different muscular dystrophies. Biomarker genes selected at the 5% confidence level from temporal Hotelling pairwise tests, whereby each strain of muscular dystrophy is tested for significant differences with each of the other strains.", "structure": {"pmcid": "PMC1450310", "section_index": 7, "section_title": "Analysis of muscular dystrophy dataset", "row_count": 31, "column_count": 9}, "table": {"label": "Table 1", "caption": "Biomarker genes for the different muscular dystrophies. 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Interestingly, also the Gtl2 gene (the murine homologue of the human MEG3 gene), which is", "ns observed in the time series of MDX and WT mice were also found in the qPCR experiment (Figure 4,", "icroarray data from wild-type mice and three mouse strains with different forms of muscular dys"], "order_basis": "paper_text_order:941", "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": 0.99, "evidence": ["genes. The R code is available from V.V. The microarray data have been submitted to GEO under series", "ing T2-test with second order polynomials on microarray data from wild-type mice and three mouse str", "due to technical artefacts arising from the microarray technology. We did so by determining the tem", "differences in heights of the curves in the microarray and qPCR experiments. Interestingly, also th"], "order_basis": "paper_text_order:2180", "id": "assay:2"}, {"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": ["dent quantitative reverse-transcription PCR (qPCR) technique. Distribution of P-values. P-valu", "iddle panel). The trend was confirmed by the qPCR assay (right panel). However, in the qPCR as", "he qPCR assay (right panel). However, in the qPCR assay, an even sharper drop in expression fr", "heights of the curves in the microarray and qPCR experiments. Interestingly, also the Gtl2 ge"], "order_basis": "paper_text_order:3897", "id": "assay:3"}]}