A Method for Avoiding Bias from Feature Selection with Application to Naive Bayes Classification Models

For many classification and regression problems, a large number of features are available for possible use - this is typical of DNA microarray data on gene expression, for example. Often, for computational or other reasons, only a small subset of these features are selected for use in a model, based on some simple measure such as correlation with the response variable. This procedure may introduce an optimistic bias, however, in which the response variable appears to be more predictable than it actually is, because the high correlation of the selected features with the response may be partly or wholely due to chance. We show how this bias can be avoided when using a Bayesian model for the joint distribution of features and response. The crucial insight is that even if we forget the exact values of the unselected features, we should retain, and condition on, the knowledge that their correlation with the response was too small for them to be selected. In this paper we describe how this idea can be implemented for ``naive Bayes'' models of binary data. Experiments with simulated data confirm that this method avoids bias due to feature selection. We also apply the naive Bayes model to subsets of data relating gene expression to colon cancer, and find that correcting for bias from feature selection does improve predictive performance

Discriminative Gene Selection Employing Linear Regression Model

Microarray datasets enables the analysis of expression of thousands of genes across hundreds of samples. Usually classifiers do not perform well for large number of features (genes) as is the case of microarray datasets. That is why a small number of informative and discriminative features are always desirable for efficient classification. Many existing feature selection approaches have been proposed which attempts sample classification based on the analysis of gene expression values. In this paper a linear regression based feature selection algorithm for two class microarray datasets has been developed which divides the training dataset into two subtypes based on the class information. Using one of the classes as the base condition, a linear regression based model is developed. Using this regression model the divergence of each gene across the two classes are calculated and thus genes with higher divergence values are selected as important features from the second subtype of the training data. The classification performance of the proposed approach is evaluated with SVM, Random Forest and AdaBoost classifiers. Results show that the proposed approach provides better accuracy values compared to other existing approaches i.e. ReliefF, CFS, decision tree based attribute selector and attribute selection using correlation analysis

Unlocking the Potential of the CA2, CA7, and ITM2C Gene Signatures for the Early Detection of Colorectal Cancer: A Comprehensive Analysis of RNA-Seq Data by Utilizing Machine Learning Algorithms

Colorectal cancer affects the colon or rectum and is a common global health issue, with 1.1 million new cases occurring yearly. The study aimed to identify gene signatures for the early detection of CRC using machine learning (ML) algorithms utilizing gene expression data. The TCGA-CRC and GSE50760 datasets were pre-processed and subjected to feature selection using the LASSO method in combination with five ML algorithms: Adaboost, Random Forest (RF), Logistic Regression (LR), Gaussian Naive Bayes (GNB), and Support Vector Machine (SVM). The important features were further analyzed for gene expression, correlation, and survival analyses. Validation of the external dataset GSE142279 was also performed. The RF model had the best classification accuracy for both datasets. A feature selection process resulted in the identification of 12 candidate genes, which were subsequently reduced to 3 (CA2, CA7, and ITM2C) through gene expression and correlation analyses. These three genes achieved 100% accuracy in an external dataset. The AUC values for these genes were 99.24%, 100%, and 99.5%, respectively. The survival analysis showed a significant logrank p-value of 0.044 for the final gene signatures. The analysis of tumor immunocyte infiltration showed a weak correlation with the expression of the gene signatures. CA2, CA7, and ITM2C can serve as gene signatures for the early detection of CRC and may provide valuable information for prognostic and therapeutic decision making. Further research is needed to fully understand the potential of these genes in the context of CRC

Two-stage Gene Selection and Classification for a High-Dimensional Microarray Data

Microarray technology has provided benefits for cancer diagnosis and classification. However, classifying cancer using microarray data is confronted with difficulty since the dataset has high dimensions. One strategy for dealing with the dimensionality problem is to make a feature selection before modeling. Lasso is a common regularization method to reduce the number of features or predictors. However, Lasso remains too many features at the optimum regularization parameter. Therefore, feature selection can be continued to the second stage. We proposed Classification and Regression Tree (CART) for feature selection on the second stage which can also produce a classification model. We used a dataset which comparing gene expression in breast tumor tissues and other tumor tissues. This dataset has 10,936 predictor variables and 1,545 observations. The results of this study were the proposed method able to produce a few numbers of selected genes but gave high accuracy. The model also acquired in line with the Oncogenomics Theory by the obtained of GATA3 to split the root node of the decision tree model. GATA3 has become an important marker for breast tumors

Identification of Prognostic Genes and Gene Sets for Early-Stage Non-Small Cell Lung Cancer Using Bi-Level Selection Methods

In contrast to feature selection and gene set analysis, bi-level selection is a process of selecting not only important gene sets but also important genes within those gene sets. Depending on the order of selections, a bi-level selection method can be classified into three categories – forward selection, which first selects relevant gene sets followed by the selection of relevant individual genes; backward selection which takes the reversed order; and simultaneous selection, which performs the two tasks simultaneously usually with the aids of a penalized regression model. To test the existence of subtype-specific prognostic genes for non-small cell lung cancer (NSCLC), we had previously proposed the Cox-filter method that examines the association between patients’ survival time after diagnosis with one specific gene, the disease subtypes, and their interaction terms. In this study, we further extend it to carry out forward and backward bi-level selection. Using simulations and a NSCLC application, we demonstrate that the forward selection outperforms the backward selection and other relevant algorithms in our setting. Both proposed methods are readily understandable and interpretable. Therefore, they represent useful tools for the researchers who are interested in exploring the prognostic value of gene expression data for specific subtypes or stages of a disease

Novel Methods of Biomarker Discovery and Predictive Modeling using Random Forest

abstract: Random forest (RF) is a popular and powerful technique nowadays. It can be used for classification, regression and unsupervised clustering. In its original form introduced by Leo Breiman, RF is used as a predictive model to generate predictions for new observations. Recent researches have proposed several methods based on RF for feature selection and for generating prediction intervals. However, they are limited in their applicability and accuracy. In this dissertation, RF is applied to build a predictive model for a complex dataset, and used as the basis for two novel methods for biomarker discovery and generating prediction interval. Firstly, a biodosimetry is developed using RF to determine absorbed radiation dose from gene expression measured from blood samples of potentially exposed individuals. To improve the prediction accuracy of the biodosimetry, day-specific models were built to deal with day interaction effect and a technique of nested modeling was proposed. The nested models can fit this complex data of large variability and non-linear relationships. Secondly, a panel of biomarkers was selected using a data-driven feature selection method as well as handpick, considering prior knowledge and other constraints. To incorporate domain knowledge, a method called Know-GRRF was developed based on guided regularized RF. This method can incorporate domain knowledge as a penalized term to regulate selection of candidate features in RF. It adds more flexibility to data-driven feature selection and can improve the interpretability of models. Know-GRRF showed significant improvement in cross-species prediction when cross-species correlation was used to guide selection of biomarkers. The method can also compete with existing methods using intrinsic data characteristics as alternative of domain knowledge in simulated datasets. Lastly, a novel non-parametric method, RFerr, was developed to generate prediction interval using RF regression. This method is widely applicable to any predictive models and was shown to have better coverage and precision than existing methods on the real-world radiation dataset, as well as benchmark and simulated datasets.Dissertation/ThesisDoctoral Dissertation Biomedical Informatics 201

Risk prediction for prostate cancer recurrence through regularized estimation with simultaneous adjustment for nonlinear clinical effects

In biomedical studies it is of substantial interest to develop risk prediction scores using high-dimensional data such as gene expression data for clinical endpoints that are subject to censoring. In the presence of well-established clinical risk factors, investigators often prefer a procedure that also adjusts for these clinical variables. While accelerated failure time (AFT) models are a useful tool for the analysis of censored outcome data, it assumes that covariate effects on the logarithm of time-to-event are linear, which is often unrealistic in practice. We propose to build risk prediction scores through regularized rank estimation in partly linear AFT models, where high-dimensional data such as gene expression data are modeled linearly and important clinical variables are modeled nonlinearly using penalized regression splines. We show through simulation studies that our model has better operating characteristics compared to several existing models. In particular, we show that there is a nonnegligible effect on prediction as well as feature selection when nonlinear clinical effects are misspecified as linear. This work is motivated by a recent prostate cancer study, where investigators collected gene expression data along with established prognostic clinical variables and the primary endpoint is time to prostate cancer recurrence.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS458 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Inferring RBP-mediated regulation in lung squamous cell carcinoma

RNA-binding proteins (RBPs) play key roles in post-transcriptional regulation of mRNAs. Dysregulations in RBP-mediated mechanisms have been found to be associated with many steps of cancer initiation and progression. Despite this, previous studies of gene expression in cancer have ignored the effect of RBPs. To this end, we developed a lasso regression model that predicts gene expression in cancer by incorporating RBP-mediated regulation as well as the effects of other well-studied factors such as copy-number variation, DNA methylation, TFs and miRNAs. As a case study, we applied our model to Lung squamous cell carcinoma (LUSC) data as we found that there are several RBPs differentially expressed in LUSC. Including RBP-mediated regulatory effects in addition to the other features significantly increased the Spearman rank correlation between predicted and measured expression of held-out genes. Using a feature selection procedure that accounts for the adaptive search employed by lasso regularization, we identified the candidate regulators in LUSC. Remarkably, several of these candidate regulators are RBPs. Furthermore, majority of the candidate regulators have been previously found to be associated with lung cancer. To investigate the mechanisms that are controlled by these regulators, we predicted their target gene sets based on our model. We validated the target gene sets by comparing against experimentally verified targets. Our results suggest that the future studies of gene expression in cancer must consider the effect of RBP-mediated regulation.No sponso

Modified Logistic Regression Models Using Gene Coexpression and Clinical Features to Predict Prostate Cancer Progression

Predicting disease progression is one of the most challenging problems in prostate cancer research. Adding gene expression data to prediction models that are based on clinical features has been proposed to improve accuracy. In the current study, we applied a logistic regression (LR) model combining clinical features and gene co-expression data to improve the accuracy of the prediction of prostate cancer progression. The top-scoring pair (TSP) method was used to select genes for the model. The proposed models not only preserved the basic properties of the TSP algorithm but also incorporated the clinical features into the prognostic models. Based on the statistical inference with the iterative cross validation, we demonstrated that prediction LR models that included genes selected by the TSP method provided better predictions of prostate cancer progression than those using clinical variables only and/or those that included genes selected by the one-gene-at-a-time approach. Thus, we conclude that TSP selection is a useful tool for feature (and/or gene) selection to use in prognostic models and our model also provides an alternative for predicting prostate cancer progression