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Evaluating machine learning methodologies for identification of cancer driver genes.

ABSTRACT: Cancer is driven by distinctive sorts of changes and basic variations in genes. Recognizing cancer driver genes is basic for accurate oncological analysis. Numerous methodologies to distinguish and identify drivers presently exist, but efficient tools to combine and optimize them on huge datasets are few. Most strategies for prioritizing transformations depend basically on frequency-based criteria. Strategies are required to dependably prioritize organically dynamic driver changes over inert passengers in high-throughput sequencing cancer information sets. This study proposes a model namely PCDG-Pred which works as a utility capable of distinguishing cancer driver and passenger attributes of genes based on sequencing data. Keeping in view the significance of the cancer driver genes an efficient method is proposed to identify the cancer driver genes. Further, various validation techniques are applied at different levels to establish the effectiveness of the model and to obtain metrics like accuracy, Mathew's correlation coefficient, sensitivity, and specificity. The results of the study strongly indicate that the proposed strategy provides a fundamental functional advantage over other existing strategies for cancer driver genes identification. Subsequently, careful experiments exhibit that the accuracy metrics obtained for self-consistency, independent set, and cross-validation tests are 91.08%., 87.26%, and 92.48% respectively.

SUBMITTER: Malebary SJ

PROVIDER: S-EPMC8192921 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Colorectal cancer (CRC) is the third leading cause of cancer-related death and the fourth most commonly diagnosed cancer worldwide. Due to a lack of diagnostic biomarkers and understanding of the underlying molecular mechanisms, CRC's mortality rate continues to grow. CRC occurrence and progression are dynamic processes. The expression levels of specific molecules vary at various stages of CRC, rendering its early detection and diagnosis challenging and the need for identifying accurate and meaningful CRC biomarkers more pressing. The advances in high-throughput sequencing technologies have been used to explore novel gene expression, targeted treatments, and colon cancer pathogenesis. Such approaches are routinely being applied and result in large datasets whose analysis is increasingly becoming dependent on machine learning (ML) algorithms that have been demonstrated to be computationally efficient platforms for the identification of variables across such high-dimensional datasets. We developed a novel ML-based experimental design to study CRC gene associations. Six different machine learning methods were employed as classifiers to identify genes that can be used as diagnostics for CRC using gene expression and clinical datasets. The accuracy, sensitivity, specificity, F1 score, and area under receiver operating characteristic (AUROC) curve were derived to explore the differentially expressed genes (DEGs) for CRC diagnosis. Gene ontology enrichment analyses of these DEGs were performed and predicted gene signatures were linked with miRNAs. We evaluated six machine learning classification methods (Adaboost, ExtraTrees, logistic regression, naïve Bayes classifier, random forest, and XGBoost) across different combinations of training and test datasets over GEO datasets. The accuracy and the AUROC of each combination of training and test data with different algorithms were used as comparison metrics. Random forest (RF) models consistently performed better than other models. In total, 34 genes were identified and used for pathway and gene set enrichment analysis. Further mapping of the 34 genes with miRNA identified interesting miRNA hubs genes. We identified 34 genes with high accuracy that can be used as a diagnostics panel for CRC.

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Evaluating machine learning methodologies for identification of cancer driver genes.

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