A new statistical method for curve group analysis of longitudinal gene expression data illustrated for breast cancer in the NOWAC postgenome cohort as a proof of principle.
Background: The understanding of changes in temporal processes related to human carcinogenesis is limited. One approach for prospective functional genomic studies is to compile trajectories of differential expression of genes, based on measurements from many case-control pairs. We propose a new stat...
| Publicado en: | BMC Medical Research Methodology Vol. 16; pp. 1 - 13 |
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| Autores principales: | , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
BioMed Central
3/5/2016
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=113547025&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 113547025 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14712288 1CI1 jtl: BMC Medical Research Methodology issn: 14712288 maglogo: N pubinfo: dt: 3/5/2016 vid: 16 pid: 24147 pub: BioMed Central artinfo: ui: 113547025 113547025 NLM26944545 113547025 10.1186/s12874-016-0129-z NLM26944545 PMC4779232 113547025 ppf: 1 ppct: 12 formats: tig: atl: A new statistical method for curve group analysis of longitudinal gene expression data illustrated for breast cancer in the NOWAC postgenome cohort as a proof of principle. aug: au: Lund, Eiliv Holden, Lars Bøvelstad, Hege Plancade, Sandra Mode, Nicolle Günther, Clara-Cecilie Nuel, Gregory Thalabard, Jean-Christophe Holden, Marit affil: Department of Community Medicine, Pb. 5060, UiT The Arctic University of Norway, 9037 Tromsø, Norway sug: subj: Data Collection Models, Statistical Early Detection of Cancer Methods Disease Susceptibility Epidemiology Breast Neoplasms Gene Expression Profiling Statistics and Numerical Data Breast Neoplasms Epidemiology Prospective Studies Sensitivity and Specificity Incidence Gene Expression Profiling Methods Female Adult Human Reference Values Norway Age Factors Genes Middle Age Aged Risk Assessment Case Control Studies Validation Studies Comparative Studies Evaluation Research Multicenter Studies Clinical Assessment Tools Adult: 19-44 years Middle Aged: 45-64 years Aged: 65+ years Female ab: Background: The understanding of changes in temporal processes related to human carcinogenesis is limited. One approach for prospective functional genomic studies is to compile trajectories of differential expression of genes, based on measurements from many case-control pairs. We propose a new statistical method that does not assume any parametric shape for the gene trajectories.Methods: The trajectory of a gene is defined as the curve representing the changes in gene expression levels in the blood as a function of time to cancer diagnosis. In a nested case-control design it consists of differences in gene expression levels between cases and controls. Genes can be grouped into curve groups, each curve group corresponding to genes with a similar development over time. The proposed new statistical approach is based on a set of hypothesis testing that can determine whether or not there is development in gene expression levels over time, and whether this development varies among different strata. Curve group analysis may reveal significant differences in gene expression levels over time among the different strata considered. This new method was applied as a "proof of concept" to breast cancer in the Norwegian Women and Cancer (NOWAC) postgenome cohort, using blood samples collected prospectively that were specifically preserved for transcriptomic analyses (PAX tube). Cohort members diagnosed with invasive breast cancer through 2009 were identified through linkage to the Cancer Registry of Norway, and for each case a random control from the postgenome cohort was also selected, matched by birth year and time of blood sampling, to create a case-control pair. After exclusions, 441 case-control pairs were available for analyses, in which we considered strata of lymph node status at time of diagnosis and time of diagnosis with respect to breast cancer screening visits.Results: The development of gene expression levels in the NOWAC postgenome cohort varied in the last years before breast cancer diagnosis, and this development differed by lymph node status and participation in the Norwegian Breast Cancer Screening Program. The differences among the investigated strata appeared larger in the year before breast cancer diagnosis compared to earlier years.Conclusions: This approach shows good properties in term of statistical power and type 1 error under minimal assumptions. When applied to a real data set it was able to discriminate between groups of genes with non-linear similar patterns before diagnosis. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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