Elephant Search with Deep Learning for Microarray Data Analysis

Even though there is a plethora of research in Microarray gene expression data analysis, still, it poses challenges for researchers to effectively and efficiently analyze the large yet complex expression of genes. The feature (gene) selection method is of paramount importance for understanding the differences in biological and non-biological variation between samples. In order to address this problem, a novel elephant search (ES) based optimization is proposed to select best gene expressions from the large volume of microarray data. Further, a promising machine learning method is envisioned to leverage such high dimensional and complex microarray dataset for extracting hidden patterns inside to make a meaningful prediction and most accurate classification. In particular, stochastic gradient descent based Deep learning (DL) with softmax activation function is then used on the reduced features (genes) for better classification of different samples according to their gene expression levels. The experiments are carried out on nine most popular Cancer microarray gene selection datasets, obtained from UCI machine learning repository. The empirical results obtained by the proposed elephant search based deep learning (ESDL) approach are compared with most recent published article for its suitability in future Bioinformatics research.Comment: 12 pages, 5 Tabl

Machine Learning and Integrative Analysis of Biomedical Big Data.

Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues

Microarray Data Mining and Gene Regulatory Network Analysis

The novel molecular biological technology, microarray, makes it feasible to obtain quantitative measurements of expression of thousands of genes present in a biological sample simultaneously. Genome-wide expression data generated from this technology are promising to uncover the implicit, previously unknown biological knowledge. In this study, several problems about microarray data mining techniques were investigated, including feature(gene) selection, classifier genes identification, generation of reference genetic interaction network for non-model organisms and gene regulatory network reconstruction using time-series gene expression data. The limitations of most of the existing computational models employed to infer gene regulatory network lie in that they either suffer from low accuracy or computational complexity. To overcome such limitations, the following strategies were proposed to integrate bioinformatics data mining techniques with existing GRN inference algorithms, which enables the discovery of novel biological knowledge. An integrated statistical and machine learning (ISML) pipeline was developed for feature selection and classifier genes identification to solve the challenges of the curse of dimensionality problem as well as the huge search space. Using the selected classifier genes as seeds, a scale-up technique is applied to search through major databases of genetic interaction networks, metabolic pathways, etc. By curating relevant genes and blasting genomic sequences of non-model organisms against well-studied genetic model organisms, a reference gene regulatory network for less-studied organisms was built and used both as prior knowledge and model validation for GRN reconstructions. Networks of gene interactions were inferred using a Dynamic Bayesian Network (DBN) approach and were analyzed for elucidating the dynamics caused by perturbations. Our proposed pipelines were applied to investigate molecular mechanisms for chemical-induced reversible neurotoxicity

Assessment of SVM Reliability for Microarray Data Analysis

The goal of our research is to provide techniques that can assess and validate the results of SVM-based analysis of microarray data. We present preliminary results of the effect of mislabeled training samples. We conducted several systematic experiments on artificial and real medical data using SVMs. We systematically flipped the labels of a fraction of the training data. We show that a relatively small number of mislabeled examples can dramatically decrease the performance as visualized on the ROC graphs. This phenomenon persists even if the dimensionality of the input space is drastically decreased, by using for example feature selection. Moreover we show that for SVM recursive feature elimination, even a small fraction of mislabeled samples can completely change the resulting set of genes. This work is an extended version of the previous paper [MBN04]

Mixtures of Spatial Spline Regressions

We present an extension of the functional data analysis framework for univariate functions to the analysis of surfaces: functions of two variables. The spatial spline regression (SSR) approach developed can be used to model surfaces that are sampled over a rectangular domain. Furthermore, combining SSR with linear mixed effects models (LMM) allows for the analysis of populations of surfaces, and combining the joint SSR-LMM method with finite mixture models allows for the analysis of populations of surfaces with sub-family structures. Through the mixtures of spatial splines regressions (MSSR) approach developed, we present methodologies for clustering surfaces into sub-families, and for performing surface-based discriminant analysis. The effectiveness of our methodologies, as well as the modeling capabilities of the SSR model are assessed through an application to handwritten character recognition

A review on recent progress in machine learning and deep learning methods for cancer classification on gene expression data

Data-driven model with predictive ability are important to be used in medical and healthcare. However, the most challenging task in predictive modeling is to construct a prediction model, which can be addressed using machine learning (ML) methods. The methods are used to learn and trained the model using a gene expression dataset without being programmed explicitly. Due to the vast amount of gene expression data, this task becomes complex and time consuming. This paper provides a recent review on recent progress in ML and deep learning (DL) for cancer classification, which has received increasing attention in bioinformatics and computational biology. The development of cancer classification methods based on ML and DL is mostly focused on this review. Although many methods have been applied to the cancer classification problem, recent progress shows that most of the successful techniques are those based on supervised and DL methods. In addition, the sources of the healthcare dataset are also described. The development of many machine learning methods for insight analysis in cancer classification has brought a lot of improvement in healthcare. Currently, it seems that there is highly demanded further development of efficient classification methods to address the expansion of healthcare applications

Sparse PLS discriminant analysis: biologically relevant feature selection and graphical displays for multiclass problems

Background: Variable selection on high throughput biological data, such as gene expression or single nucleotide polymorphisms (SNPs), becomes inevitable to select relevant information and, therefore, to better characterize diseases or assess genetic structure. There are different ways to perform variable selection in large data sets. Statistical tests are commonly used to identify differentially expressed features for explanatory purposes, whereas Machine Learning wrapper approaches can be used for predictive purposes. In the case of multiple highly correlated variables, another option is to use multivariate exploratory approaches to give more insight into cell biology, biological pathways or complex traits.Results: A simple extension of a sparse PLS exploratory approach is proposed to perform variable selection in a multiclass classification framework.Conclusions: sPLS-DA has a classification performance similar to other wrapper or sparse discriminant analysis approaches on public microarray and SNP data sets. More importantly, sPLS-DA is clearly competitive in terms of computational efficiency and superior in terms of interpretability of the results via valuable graphical outputs. sPLS-DA is available in the R package mixOmics, which is dedicated to the analysis of large biological data sets

Molecular cancer classification using an meta-sample-based regularized robust coding method

Motivation Previous studies have demonstrated that machine learning based molecular cancer classification using gene expression profiling (GEP) data is promising for the clinic diagnosis and treatment of cancer. Novel classification methods with high efficiency and prediction accuracy are still needed to deal with high dimensionality and small sample size of typical GEP data. Recently the sparse representation (SR) method has been successfully applied to the cancer classification. Nevertheless, its efficiency needs to be improved when analyzing large-scale GEP data. Results In this paper we present the meta-sample-based regularized robust coding classification (MRRCC), a novel effective cancer classification technique that combines the idea of meta-sample-based cluster method with regularized robust coding (RRC) method. It assumes that the coding residual and the coding coefficient are respectively independent and identically distributed. Similar to meta-sample-based SR classification (MSRC), MRRCC extracts a set of meta-samples from the training samples, and then encodes a testing sample as the sparse linear combination of these meta-samples. The representation fidelity is measured by the l2-norm or l1-norm of the coding residual. Conclusions Extensive experiments on publicly available GEP datasets demonstrate that the proposed method is more efficient while its prediction accuracy is equivalent to existing MSRC-based methods and better than other state-of-the-art dimension reduction based methods.This article was funded by the National Science Foundation of China on finding tumor-related driver pathway with comprehensive analysis method based on next-generation sequencing data and the dimension reduction of gene expression data based on heuristic method (grant nos. 61474267, 60973153 and 61133010) and the National Institutes of Health (NIH) Grant P01 AG12993 (PI: E. Michaelis). This article has been published as part of BMC Bioinformatics Volume 15 Supplement 15, 2014: Proceedings of the 2013 International Conference on Intelligent Computing (ICIC 2013). The full contents of the supplement are available online at http://www.biomedcentral.com/bmcbioinformatics/supplements/15/S15