scholarly journals Unsupervised Machine Learning for Data Encoding applied to Ovarian Cancer Transcriptomes

2019 ◽  
Author(s):  
Tom M George ◽  
Pietro Lio

AbstractMachine learning algorithms are revolutionising how information can be extracted from complex and high-dimensional data sets via intelligent compression. For example, unsupervised Autoen-coders train a deep neural network with a low-dimensional “bottlenecked” central layer to reconstruct input vectors. Variational Autoencoders (VAEs) have shown promise at learning meaningful latent spaces for text, image and more recently, gene-expression data. In the latter case they have been shown capable of capturing biologically relevant features such as a patients sex or tumour type. Here we train a VAE on ovarian cancer transcriptomes from The Cancer Genome Atlas and show that, in many cases, the latent spaces learns an encoding predictive of cisplatin chemotherapy resistance. We analyse the effectiveness of such an architecture to a wide range of hyperparameters as well as use a state-of-the-art clustering algorithm, t-SNE, to embed the data in a two-dimensional manifold and visualise the predictive power of the trained latent spaces. By correlating genes to resistance-predictive encodings we are able to extract biological processes likely responsible for platinum resistance. Finally we demonstrate that variational autoencoders can reliably encode gene expression data contaminated with significant amounts of Gaussian and dropout noise, a necessary feature if this technique is to be applicable to other data sets, including those in non-medical fields.

2009 ◽  
Vol 07 (04) ◽  
pp. 645-661 ◽  
Author(s):  
XIN CHEN

There is an increasing interest in clustering time course gene expression data to investigate a wide range of biological processes. However, developing a clustering algorithm ideal for time course gene express data is still challenging. As timing is an important factor in defining true clusters, a clustering algorithm shall explore expression correlations between time points in order to achieve a high clustering accuracy. Moreover, inter-cluster gene relationships are often desired in order to facilitate the computational inference of biological pathways and regulatory networks. In this paper, a new clustering algorithm called CurveSOM is developed to offer both features above. It first presents each gene by a cubic smoothing spline fitted to the time course expression profile, and then groups genes into clusters by applying a self-organizing map-based clustering on the resulting splines. CurveSOM has been tested on three well-studied yeast cell cycle datasets, and compared with four popular programs including Cluster 3.0, GENECLUSTER, MCLUST, and SSClust. The results show that CurveSOM is a very promising tool for the exploratory analysis of time course expression data, as it is not only able to group genes into clusters with high accuracy but also able to find true time-shifted correlations of expression patterns across clusters.


2021 ◽  
Author(s):  
Jingyi Zhang ◽  
Farhan Ibrahim ◽  
Doaa Altarawy ◽  
Lenwood S Heath ◽  
Sarah Tulin

Abstract BackgroundGene regulatory network (GRN) inference can now take advantage of powerful machine learning algorithms to predict the entire landscape of gene-to-gene interactions with the potential to complement traditional experimental methods in building gene networks. However, the dynamical nature of embryonic development -- representing the time-dependent interactions between thousands of transcription factors, signaling molecules, and effector genes -- is one of the most challenging arenas for GRN prediction. ResultsIn this work, we show that successful GRN predictions for developmental systems from gene expression data alone can be obtained with the Priors Enriched Absent Knowledge (PEAK) network inference algorithm. PEAK is a noise-robust method that models gene expression dynamics via ordinary differential equations and selects the best network based on information-theoretic criteria coupled with the machine learning algorithm Elastic net. We test our GRN prediction methodology using two gene expression data sets for the purple sea urchin (S. purpuratus) and cross-check our results against existing GRN models that have been constructed and validated by over 30 years of experimental results. Our results found a remarkably high degree of sensitivity in identifying known gene interactions in the network (maximum 76.32%). We also generated 838 novel predictions for interactions that have not yet been described, which provide a resource for researchers to use to further complete the sea urchin GRN. ConclusionsGRN predictions that match known gene interactions can be produced using gene expression data alone from developmental time series experiments.


2013 ◽  
pp. 1626-1641
Author(s):  
Anasua Sarkar ◽  
Ujjwal Maulik

Identification of cancer subtypes is the central goal in the cancer gene expression data analysis. Modified symmetry-based clustering is an unsupervised learning technique for detecting symmetrical convex or non-convex shaped clusters. To enable fast automatic clustering of cancer tissues (samples), in this chapter, the authors propose a rough set based hybrid approach for modified symmetry-based clustering algorithm. A natural basis for analyzing gene expression data using the symmetry-based algorithm is to group together genes with similar symmetrical patterns of microarray expressions. Rough-set theory helps in faster convergence and initial automatic optimal classification, thereby solving the problem of unknown knowledge of number of clusters in gene expression measurement data. For rough-set-theoretic decision rule generation, each cluster is classified using heuristically searched optimal reducts to overcome overlapping cluster problem. The rough modified symmetry-based clustering algorithm is compared with another newly implemented rough-improved symmetry-based clustering algorithm and existing K-Means algorithm over five benchmark cancer gene expression data sets, to demonstrate its superiority in terms of validity. The statistical analyses are also performed to establish the significance of this rough modified symmetry-based clustering approach.


Author(s):  
Anasua Sarkar ◽  
Ujjwal Maulik

Identification of cancer subtypes is the central goal in the cancer gene expression data analysis. Modified symmetry-based clustering is an unsupervised learning technique for detecting symmetrical convex or non-convex shaped clusters. To enable fast automatic clustering of cancer tissues (samples), in this chapter, the authors propose a rough set based hybrid approach for modified symmetry-based clustering algorithm. A natural basis for analyzing gene expression data using the symmetry-based algorithm is to group together genes with similar symmetrical patterns of microarray expressions. Rough-set theory helps in faster convergence and initial automatic optimal classification, thereby solving the problem of unknown knowledge of number of clusters in gene expression measurement data. For rough-set-theoretic decision rule generation, each cluster is classified using heuristically searched optimal reducts to overcome overlapping cluster problem. The rough modified symmetry-based clustering algorithm is compared with another newly implemented rough-improved symmetry-based clustering algorithm and existing K-Means algorithm over five benchmark cancer gene expression data sets, to demonstrate its superiority in terms of validity. The statistical analyses are also performed to establish the significance of this rough modified symmetry-based clustering approach.


2021 ◽  
Vol 12 (2) ◽  
pp. 2422-2439

Cancer classification is one of the main objectives for analyzing big biological datasets. Machine learning algorithms (MLAs) have been extensively used to accomplish this task. Several popular MLAs are available in the literature to classify new samples into normal or cancer populations. Nevertheless, most of them often yield lower accuracies in the presence of outliers, which leads to incorrect classification of samples. Hence, in this study, we present a robust approach for the efficient and precise classification of samples using noisy GEDs. We examine the performance of the proposed procedure in a comparison of the five popular traditional MLAs (SVM, LDA, KNN, Naïve Bayes, Random forest) using both simulated and real gene expression data analysis. We also considered several rates of outliers (10%, 20%, and 50%). The results obtained from simulated data confirm that the traditional MLAs produce better results through our proposed procedure in the presence of outliers using the proposed modified datasets. The further transcriptome analysis found the significant involvement of these extra features in cancer diseases. The results indicated the performance improvement of the traditional MLAs with our proposed procedure. Hence, we propose to apply the proposed procedure instead of the traditional procedure for cancer classification.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Elisabetta Manduchi ◽  
Weixuan Fu ◽  
Joseph D. Romano ◽  
Stefano Ruberto ◽  
Jason H. Moore

Abstract Background A typical task in bioinformatics consists of identifying which features are associated with a target outcome of interest and building a predictive model. Automated machine learning (AutoML) systems such as the Tree-based Pipeline Optimization Tool (TPOT) constitute an appealing approach to this end. However, in biomedical data, there are often baseline characteristics of the subjects in a study or batch effects that need to be adjusted for in order to better isolate the effects of the features of interest on the target. Thus, the ability to perform covariate adjustments becomes particularly important for applications of AutoML to biomedical big data analysis. Results We developed an approach to adjust for covariates affecting features and/or target in TPOT. Our approach is based on regressing out the covariates in a manner that avoids ‘leakage’ during the cross-validation training procedure. We describe applications of this approach to toxicogenomics and schizophrenia gene expression data sets. The TPOT extensions discussed in this work are available at https://github.com/EpistasisLab/tpot/tree/v0.11.1-resAdj. Conclusions In this work, we address an important need in the context of AutoML, which is particularly crucial for applications to bioinformatics and medical informatics, namely covariate adjustments. To this end we present a substantial extension of TPOT, a genetic programming based AutoML approach. We show the utility of this extension by applications to large toxicogenomics and differential gene expression data. The method is generally applicable in many other scenarios from the biomedical field.


2020 ◽  
Author(s):  
Elisabetta Manduchi ◽  
Weixuan Fu ◽  
Joseph D. Romano ◽  
Stefano Ruberto ◽  
Jason H. Moore

AbstractBackgroundA typical task in bioinformatics consists of identifying which features are associated with a target outcome of interest and building a predictive model. Automated machine learning (AutoML) systems such as the Tree-based Pipeline Optimization Tool (TPOT) constitute an appealing approach to this end. However, in biomedical data, there are often baseline characteristics of the subjects in a study or batch effects that need to be adjusted for in order to better isolate the effects of the features of interest on the target. Thus, the ability to perform covariate adjustments becomes particularly important for applications of AutoML to biomedical big data analysis.ResultsWe present an approach to adjust for covariates affecting features and/or target in TPOT. Our approach is based on regressing out the covariates in a manner that avoids ‘leakage’ during the cross-validation training procedure. We then describe applications of this approach to toxicogenomics and schizophrenia gene expression data sets. The TPOT extensions discussed in this work are available at https://github.com/EpistasisLab/tpot/tree/v0.11.1-resAdj.ConclusionsIn this work, we address an important need in the context of AutoML, which is particularly crucial for applications to bioinformatics and medical informatics, namely covariate adjustments. To this end we present a substantial extension of TPOT, a genetic programming based AutoML approach. We show the utility of this extension by applications to large toxicogenomics and differential gene expression data. The method is generally applicable in many other scenarios from the biomedical field.


Author(s):  
Ching Wei Wang

One of the most active areas of research in supervised machine learning has been to study methods for constructing good ensembles of classifiers. The main discovery is that the ensemble classifier often performs much better than single classifiers that make them up. Recent researches (Dettling, 2004, Tan & Gilbert, 2003) have confirmed the utility of ensemble machine learning algorithms for gene expression analysis. The motivation of this work is to investigate a suitable machine learning algorithm for classification and prediction on gene expression data. The research starts with analyzing the behavior and weaknesses of three popular ensemble machine learning methods—Bagging, Boosting, and Arcing—followed by presentation of a new ensemble machine learning algorithm. The proposed method is evaluated with the existing ensemble machine learning algorithms over 12 gene expression datasets (Alon et al., 1999; Armstrong et al., 2002; Ash et al., 2000; Catherine et al., 2003; Dinesh et al., 2002; Gavin et al., 2002; Golub et al., 1999; Scott et al., 2002; van ’t Veer et al., 2002; Yeoh et al., 2002; Zembutsu et al., 2002). The experimental results show that the proposed algorithm greatly outperforms existing methods, achieving high accuracy in classification. The outline of this chapter is as follows: Ensemble machine learning approach and three popular ensembles (i.e., Bagging, Boosting, and Arcing) are introduced first in the Background section; second, the analyses on existing ensembles, details of the proposed algorithm, and experimental results are presented in Method section, followed by discussions on the future trends and conclusion.


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