Biomarker Discovery and Redundancy Reduction towards Classification using a Multi-factorial MALDI-TOF MS T2DM Mouse Model Dataset

• Main Authors: Al-Hasani Hadi, Beule Dieter, Dreja Tanja, Chadt Alexandra, Tiss Ali, Towers Mark W, Smith Celia J, Kleinjung Frank, Bauer Chris, Reinert Knut, Schuchhardt Johannes, Cramer Rainer
• Format: Article
• Language: English
• Published: BMC 2011-05-01
• Series: BMC Bioinformatics
• Online Access: http://www.biomedcentral.com/1471-2105/12/140

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p>