Dataset Information

NeoMutate: an ensemble machine learning framework for the prediction of somatic mutations in cancer.

ABSTRACT: BACKGROUND:The accurate screening of tumor genomic landscapes for somatic mutations using high-throughput sequencing involves a crucial step in precise clinical diagnosis and targeted therapy. However, the complex inherent features of cancer tissue, especially, tumor genetic intra-heterogeneity coupled with the problem of sequencing and alignment artifacts, makes somatic variant calling a challenging task. Current variant filtering strategies, such as rule-based filtering and consensus voting of different algorithms, have previously helped to increase specificity, although comes at the cost of sensitivity. METHODS:In light of this, we have developed the NeoMutate framework which incorporates 7 supervised machine learning (ML) algorithms to exploit the strengths of multiple variant callers, using a non-redundant set of biological and sequence features. We benchmarked NeoMutate by simulating more than 10,000 bona fide cancer-related mutations into three well-characterized Genome in a Bottle (GIAB) reference samples. RESULTS:A robust and exhaustive evaluation of NeoMutate's performance based on 5-fold cross validation experiments, in addition to 3 independent tests, demonstrated a substantially improved variant detection accuracy compared to any of its individual composite variant callers and consensus calling of multiple tools. CONCLUSIONS:We show here that integrating multiple tools in an ensemble ML layer optimizes somatic variant detection rates, leading to a potentially improved variant selection framework for the diagnosis and treatment of cancer.

SUBMITTER: Anzar I

PROVIDER: S-EPMC6524241 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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NeoMutate: an ensemble machine learning framework for the prediction of somatic mutations in cancer.

Anzar Irantzu I Sverchkova Angelina A Stratford Richard R Clancy Trevor T

BMC medical genomics 20190516 1

<h4>Background</h4>The accurate screening of tumor genomic landscapes for somatic mutations using high-throughput sequencing involves a crucial step in precise clinical diagnosis and targeted therapy. However, the complex inherent features of cancer tissue, especially, tumor genetic intra-heterogeneity coupled with the problem of sequencing and alignment artifacts, makes somatic variant calling a challenging task. Current variant filtering strategies, such as rule-based filtering and consensus v ...[more]

PMID: 31096972

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Project description:BACKGROUND:In plants, long non-protein coding RNAs are believed to have essential roles in development and stress responses. However, relative to advances on discerning biological roles for long non-protein coding RNAs in animal systems, this RNA class in plants is largely understudied. With comparatively few validated plant long non-coding RNAs, research on this potentially critical class of RNA is hindered by a lack of appropriate prediction tools and databases. Supervised learning models trained on data sets of mostly non-validated, non-coding transcripts have been previously used to identify this enigmatic RNA class with applications largely focused on animal systems. Our approach uses a training set comprised only of empirically validated long non-protein coding RNAs from plant, animal, and viral sources to predict and rank candidate long non-protein coding gene products for future functional validation. RESULTS:Individual stochastic gradient boosting and random forest classifiers trained on only empirically validated long non-protein coding RNAs were constructed. In order to use the strengths of multiple classifiers, we combined multiple models into a single stacking meta-learner. This ensemble approach benefits from the diversity of several learners to effectively identify putative plant long non-coding RNAs from transcript sequence features. When the predicted genes identified by the ensemble classifier were compared to those listed in GreeNC, an established plant long non-coding RNA database, overlap for predicted genes from Arabidopsis thaliana, Oryza sativa and Eutrema salsugineum ranged from 51 to 83% with the highest agreement in Eutrema salsugineum. Most of the highest ranking predictions from Arabidopsis thaliana were annotated as potential natural antisense genes, pseudogenes, transposable elements, or simply computationally predicted hypothetical protein. Due to the nature of this tool, the model can be updated as new long non-protein coding transcripts are identified and functionally verified. CONCLUSIONS:This ensemble classifier is an accurate tool that can be used to rank long non-protein coding RNA predictions for use in conjunction with gene expression studies. Selection of plant transcripts with a high potential for regulatory roles as long non-protein coding RNAs will advance research in the elucidation of long non-protein coding RNA function.

Project description:BackgroundAccurate estimation of historical PM2.5 (particle matter with an aerodynamic diameter of less than 2.5μm) is critical and essential for environmental health risk assessment.ObjectivesThe aim of this study was to develop a multiple-level stacked ensemble machine learning framework for improving the estimation of the daily ground-level PM2.5 concentrations.MethodsAn innovative deep ensemble machine learning framework (DEML) was developed to estimate the daily PM2.5 concentrations. The framework has a three-stage structure: At the first stage, four base models [gradient boosting machine (GBM), support vector machine (SVM), random forest (RF), and eXtreme gradient boosting (XGBoost)] were used to generate a new data set of PM2.5 concentrations for training the next-stage learners. At the second stage, three meta-models [RF, XGBoost, and Generalized Linear Model (GLM)] were used to estimate PM2.5 concentrations using a combination of the original data set and the predictions from the first-stage models. At the third stage, a nonnegative least squares (NNLS) algorithm was employed to obtain the optimal weights for PM2.5 estimation. We took the data from 133 monitoring stations in Italy as an example to implement the DEML to predict daily PM2.5 at each 1km×1km grid cell from 2015 to 2019 across Italy. We evaluated the model performance by performing 10-fold cross-validation (CV) and compared it with five benchmark algorithms [GBM, SVM, RF, XGBoost, and Super Learner (SL)].ResultsThe results revealed that the PM2.5 prediction performance of DEML [coefficients of determination (R2)=0.87 and root mean square error (RMSE)=5.38μg/m3] was superior to any benchmark models (with R2 of 0.51, 0.76, 0.83, 0.70, and 0.83 for GBM, SVM, RF, XGBoost, and SL approach, respectively). DEML displayed reliable performance in capturing the spatiotemporal variations of PM2.5 in Italy.DiscussionThe proposed DEML framework achieved an outstanding performance in PM2.5 estimation, which could be used as a tool for more accurate environmental exposure assessment. https://doi.org/10.1289/EHP9752.

Dataset Information

NeoMutate: an ensemble machine learning framework for the prediction of somatic mutations in cancer.

Publications

NeoMutate: an ensemble machine learning framework for the prediction of somatic mutations in cancer.

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