Dataset Information

Integration of Random Forest Classifiers and Deep Convolutional Neural Networks for Classification and Biomolecular Modeling of Cancer Driver Mutations.

ABSTRACT: Development of machine learning solutions for prediction of functional and clinical significance of cancer driver genes and mutations are paramount in modern biomedical research and have gained a significant momentum in a recent decade. In this work, we integrate different machine learning approaches, including tree based methods, random forest and gradient boosted tree (GBT) classifiers along with deep convolutional neural networks (CNN) for prediction of cancer driver mutations in the genomic datasets. The feasibility of CNN in using raw nucleotide sequences for classification of cancer driver mutations was initially explored by employing label encoding, one hot encoding, and embedding to preprocess the DNA information. These classifiers were benchmarked against their tree-based alternatives in order to evaluate the performance on a relative scale. We then integrated DNA-based scores generated by CNN with various categories of conservational, evolutionary and functional features into a generalized random forest classifier. The results of this study have demonstrated that CNN can learn high level features from genomic information that are complementary to the ensemble-based predictors often employed for classification of cancer mutations. By combining deep learning-generated score with only two main ensemble-based functional features, we can achieve a superior performance of various machine learning classifiers. Our findings have also suggested that synergy of nucleotide-based deep learning scores and integrated metrics derived from protein sequence conservation scores can allow for robust classification of cancer driver mutations with a limited number of highly informative features. Machine learning predictions are leveraged in molecular simulations, protein stability, and network-based analysis of cancer mutations in the protein kinase genes to obtain insights about molecular signatures of driver mutations and enhance the interpretability of cancer-specific classification models.

SUBMITTER: Agajanian S

PROVIDER: S-EPMC6579812 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Integration of Random Forest Classifiers and Deep Convolutional Neural Networks for Classification and Biomolecular Modeling of Cancer Driver Mutations.

Agajanian Steve S Oluyemi Odeyemi O Verkhivker Gennady M GM

Frontiers in molecular biosciences 20190611

Development of machine learning solutions for prediction of functional and clinical significance of cancer driver genes and mutations are paramount in modern biomedical research and have gained a significant momentum in a recent decade. In this work, we integrate different machine learning approaches, including tree based methods, random forest and gradient boosted tree (GBT) classifiers along with deep convolutional neural networks (CNN) for prediction of cancer driver mutations in the genomic ...[more]

PMID: 31245384

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Project description:PURPOSE:Convolutional neural networks have become rapidly popular for image recognition and image analysis because of its powerful potential. In this paper, we developed a method for classifying subtypes of lung adenocarcinoma from pathological images using neural network whose that can evaluate phenotypic features from wider area to consider cellular distributions. METHODS:In order to recognize the types of tumors, we need not only to detail features of cells, but also to incorporate statistical distribution of the different types of cells. Variants of autoencoders as building blocks of pre-trained convolutional layers of neural networks are implemented. A sparse deep autoencoder which minimizes local information entropy on the encoding layer is then proposed and applied to images of size [Formula: see text]. We applied this model for feature extraction from pathological images of lung adenocarcinoma, which is comprised of three transcriptome subtypes previously defined by the Cancer Genome Atlas network. Since the tumor tissue is composed of heterogeneous cell populations, recognition of tumor transcriptome subtypes requires more information than local pattern of cells. The parameters extracted using this approach will then be used in multiple reduction stages to perform classification on larger images. RESULTS:We were able to demonstrate that these networks successfully recognize morphological features of lung adenocarcinoma. We also performed classification and reconstruction experiments to compare the outputs of the variants. The results showed that the larger input image that covers a certain area of the tissue is required to recognize transcriptome subtypes. The sparse autoencoder network with [Formula: see text] input provides a 98.9% classification accuracy. CONCLUSION:This study shows the potential of autoencoders as a feature extraction paradigm and paves the way for a whole slide image analysis tool to predict molecular subtypes of tumors from pathological features.

Dataset Information

Integration of Random Forest Classifiers and Deep Convolutional Neural Networks for Classification and Biomolecular Modeling of Cancer Driver Mutations.

Publications

Integration of Random Forest Classifiers and Deep Convolutional Neural Networks for Classification and Biomolecular Modeling of Cancer Driver Mutations.

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