Filtered selection coupled with support vector machines generate a functionally relevant prediction model for colorectal cancer

Abstract

Musa Nur Gabere,1 Mohamed Aly Hussein,1 Mohammad Azhar Aziz2 1Department of Bioinformatics, King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 2Colorectal Cancer Research Program, Department of Medical Genomics, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia Purpose: There has been considerable interest in using whole-genome expression profiles for the classification of colorectal cancer (CRC). The selection of important features is a crucial step before training a classifier.Methods: In this study, we built a model that uses support vector machine (SVM) to classify cancer and normal samples using Affymetrix exon microarray data obtained from 90 samples of 48 patients diagnosed with CRC. From the 22,011 genes, we selected the 20, 30, 50, 100, 200, 300, and 500 genes most relevant to CRC using the minimum-redundancy–maximum-relevance (mRMR) technique. With these gene sets, an SVM model was designed using four different kernel types (linear, polynomial, radial basis function [RBF], and sigmoid).Results: The best model, which used 30 genes and RBF kernel, outperformed other combinations; it had an accuracy of 84% for both ten fold and leave-one-out cross validations in discriminating the cancer samples from the normal samples. With this 30 genes set from mRMR, six classifiers were trained using random forest (RF), Bayes net (BN), multilayer perceptron (MLP), naïve Bayes (NB), reduced error pruning tree (REPT), and SVM. Two hybrids, mRMR + SVM and mRMR + BN, were the best models when tested on other datasets, and they achieved a prediction accuracy of 95.27% and 91.99%, respectively, compared to other mRMR hybrid models (mRMR + RF, mRMR + NB, mRMR + REPT, and mRMR + MLP). Ingenuity pathway analysis was used to analyze the functions of the 30 genes selected for this model and their potential association with CRC: CDH3, CEACAM7, CLDN1, IL8, IL6R, MMP1, MMP7, and TGFB1 were predicted to be CRC biomarkers.Conclusion: This model could be used to further develop a diagnostic tool for predicting CRC based on gene expression data from patient samples. Keywords: colorectal cancer, support vector machines, exon microarray, minimum redundancy maximum relevance, predictive model, pathway analysis, biomarkers