Discovering robust protein biomarkers for disease from relative expression reversals in 2-D DIGE data.
This study assesses the ability of a novel family of machine learning algorithms to identify changes in relative protein expression levels, measured using 2-D DIGE data, which support accurate class prediction. The analysis was done using a training set of 36 total cellular lysates comprised of six normal and three cancer biological replicates (the remaining are technical replicates) and a validation set of four normal and two cancer samples. Protein samples were separated by 2-D DIGE and expression was quantified using DeCyder-2D Differential Analysis Software. The relative expression reversal (RER) classifier correctly classified 9/9 training biological samples (p<0.022) as estimated using a modified version of leave one out cross validation and 6/6 validation samples. The classification rule involved comparison of expression levels for a single pair of protein spots, tropomyosin isoforms and alpha-enolase, both of which have prior association as potential biomarkers in cancer. The data was also analyzed using algorithms similar to those found in the extended data analysis package of DeCyder software. We propose that by accounting for sources of within- and between-gel variation, RER classifiers applied to 2-D DIGE data provide a useful approach for identifying biomarkers that discriminate among protein samples of interest.
Anderson
Troy J
TJ
Center for Cardiovascular Bioinformatics and Modeling and The Institute of Computational Medicine, Johns Hopkins University, Baltimore, MD 21218, USA. troy_anderson@jhu.edu
Tchernyshyov
Irina
I
Diez
Roberto
R
Cole
Robert N
RN
Geman
Donald
D
Dang
Chi V
CV
Winslow
Raimond L
RL
D000465:Algorithms; D014408:Biomarkers, Tumor / Q000032:analysis*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000032:analysis; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods*; D006801:Humans; D008969:Molecular Sequence Data; D010363:Pattern Recognition, Automated; D010751:Phosphopyruvate Hydratase / Q000032:analysis; D020033:Protein Isoforms / Q000032:analysis; D011506:Proteins / Q000032:analysis*; D015203:Reproducibility of Results; D012984:Software; D014335:Tropomyosin / Q000032:analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D020033:Protein Isoforms; D011506:Proteins; D014335:Tropomyosin; D025521:Tumor Suppressor Proteins; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase