Identifying and Assessing Interesting Subgroups in a Heterogeneous Population.

Biological heterogeneity is common in many diseases and it is often the reason for therapeutic failures. Thus, there is great interest in classifying a disease into subtypes that have clinical significance in terms of prognosis or therapy response. One of the most popular methods to uncover unrecogn...

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Publicado en:BioMed Research International Vol. 2015; pp. 1 - 14
Autores principales: Lee, Woojoo, Alexeyenko, Andrey, Pernemalm, Maria, Guegan, Justine, Dessen, Philippe, Lazar, Vladimir, Lehtiö, Janne, Pawitan, Yudi
Formato: algorithm equations & formulas research tables/charts Journal Article
Publicado: Wiley-Blackwell 8/3/2015
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 8/3/2015
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      pub: Wiley-Blackwell
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        10.1155/2015/462549
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        atl: Identifying and Assessing Interesting Subgroups in a Heterogeneous Population.
      aug:
        au:
          Lee, Woojoo
          Alexeyenko, Andrey
          Pernemalm, Maria
          Guegan, Justine
          Dessen, Philippe
          Lazar, Vladimir
          Lehtiö, Janne
          Pawitan, Yudi
        affil: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17177 Stockholm, Sweden
      sug:
        subj:
          Population
          Research Measurement
          Cluster Analysis
          Descriptive Statistics
          Data Analysis Software
          Mathematics
          Validity
          Data Analysis
          Lung Neoplasms
          Funding Source
          Human
      ab: Biological heterogeneity is common in many diseases and it is often the reason for therapeutic failures. Thus, there is great interest in classifying a disease into subtypes that have clinical significance in terms of prognosis or therapy response. One of the most popular methods to uncover unrecognized subtypes is cluster analysis. However, classical clustering methods such as k-means clustering or hierarchical clustering are not guaranteed to produce clinically interesting subtypes. This could be because the main statistical variability—the basis of cluster generation—is dominated by genes not associated with the clinical phenotype of interest. Furthermore, a strong prognostic factor might be relevant for a certain subgroup but not for the whole population; thus an analysis of the whole sample may not reveal this prognostic factor. To address these problems we investigate methods to identify and assess clinically interesting subgroups in a heterogeneous population. The identification step uses a clustering algorithm and to assess significance we use a false discovery rate- (FDR-) based measure. Under the heterogeneity condition the standard FDR estimate is shown to overestimate the true FDR value, but this is remedied by an improved FDR estimation procedure. As illustrations, two real data examples from gene expression studies of lung cancer are provided.
      pubtype: Academic Journal
      doctype:
        algorithm
        equations & formulas
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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