Biomarker discovery and redundancy reduction towards classification using a multi-factorial MALDI-TOF MS T2DM mouse model dataset

BMC Bioinformatics. 2011 May 9:12:140. doi: 10.1186/1471-2105-12-140.

Abstract

Background: Diabetes like many diseases and biological processes is not mono-causal. On the one hand multi-factorial studies with complex experimental design are required for its comprehensive analysis. On the other hand, the data from these studies often include a substantial amount of redundancy such as proteins that are typically represented by a multitude of peptides. Coping simultaneously with both complexities (experimental and technological) makes data analysis a challenge for Bioinformatics.

Results: We present a comprehensive work-flow tailored for analyzing complex data including data from multi-factorial studies. The developed approach aims at revealing effects caused by a distinct combination of experimental factors, in our case genotype and diet. Applying the developed work-flow to the analysis of an established polygenic mouse model for diet-induced type 2 diabetes, we found peptides with significant fold changes exclusively for the combination of a particular strain and diet. Exploitation of redundancy enables the visualization of peptide correlation and provides a natural way of feature selection for classification and prediction. Classification based on the features selected using our approach performs similar to classifications based on more complex feature selection methods.

Conclusions: The combination of ANOVA and redundancy exploitation allows for identification of biomarker candidates in multi-dimensional MALDI-TOF MS profiling studies with complex experimental design. With respect to feature selection our method provides a fast and intuitive alternative to global optimization strategies with comparable performance. The method is implemented in R and the scripts are available by contacting the corresponding author.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / analysis
  • Analysis of Variance
  • Animals
  • Biomarkers / analysis*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diet
  • Hemoglobins / analysis
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Peptides / analysis
  • Proteomics / methods*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*

Substances

  • Albumins
  • Biomarkers
  • Hemoglobins
  • Peptides