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Analyzing Multifactorial RNA-Seq Experiments with DiCoExpress
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Challenges in projecting clustering results across gene expression-profiling datasets.

Lara Lusa1, Lisa M McShane, James F Reid

  • 1Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. lara.lusa@ifom-ieo-campus.it

Journal of the National Cancer Institute
|November 15, 2007
PubMed
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Mean centering gene expression data aids breast cancer subtype classification but can lead to misclassification, especially for estrogen receptor-positive samples. Careful consideration of patient population comparability is crucial for accurate subtype assignment.

Area of Science:

  • Genomics
  • Bioinformatics
  • Cancer Research

Background:

  • Gene expression microarray studies have identified distinct cancer subtypes.
  • A five-subtype molecular classification for breast cancer exists, showing clinical outcome associations.
  • The method of centroids classifies new samples based on similarity to established subtype profiles.

Purpose of the Study:

  • To assess the impact of mean centering gene expression data on breast cancer subtype classification using the method of centroids.
  • To investigate the influence of mean centering and estrogen receptor-positive (ER+) sample prevalence on ER status classification accuracy.

Main Methods:

  • Utilized previously identified centroids to assign 99 breast cancer samples (65 ER+) to five subtypes via microarray data.

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  • Evaluated the effect of gene mean centering on subtype assignment accuracy.
  • Conducted further studies varying ER+ sample proportion in test sets to assess mean centering's impact on ER status classification.
  • Main Results:

    • Mean centering improved subtype assignment for all 99 samples, aligning with known subtype marker gene expression.
    • Classification of ER+ samples alone revealed misclassifications and unexpected subtype distributions.
    • Gene mean centering for ER status classification showed high dependence on ER+ sample prevalence, an effect absent without mean centering.

    Conclusions:

    • Simple data corrections like gene mean centering can introduce biases, conflating assay effects with patient population differences.
    • Comparability of patient populations must be carefully considered before applying data normalization techniques for subtype assignment.