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

Bayesian hierarchical clustering for studying cancer gene expression data with unknown statistics

Clustering analysis is an important tool in studying gene expression data. The Bayesian hierarchical clustering (BHC) algorithm can automatically infer the number of clusters and uses Bayesian model selection to improve clustering quality. In this paper, we present an extension of the BHC algorithm. Our Gaussian BHC (GBHC) algorithm represents data as a mixture of Gaussian distributions. It uses normal-gamma distribution as a conjugate prior on the mean and precision of each of the Gaussian components. We tested GBHC over 11 cancer and 3 synthetic datasets. The results on cancer datasets show that in sample clustering, GBHC on average produces a clustering partition that is more concordant with the ground truth than those obtained from other commonly used algorithms. Furthermore, GBHC frequently infers the number of clusters that is often close to the ground truth. In gene clustering, GBHC also produces a clustering partition that is more biologically plausible than several other state-of-the-art methods. This suggests GBHC as an alternative tool for studying gene expression data. The implementation of GBHC is available at https://sites. google.com/site/gaussianbhc

SUBIC: A Supervised Bi-Clustering Approach for Precision Medicine

Traditional medicine typically applies one-size-fits-all treatment for the entire patient population whereas precision medicine develops tailored treatment schemes for different patient subgroups. The fact that some factors may be more significant for a specific patient subgroup motivates clinicians and medical researchers to develop new approaches to subgroup detection and analysis, which is an effective strategy to personalize treatment. In this study, we propose a novel patient subgroup detection method, called Supervised Biclustring (SUBIC) using convex optimization and apply our approach to detect patient subgroups and prioritize risk factors for hypertension (HTN) in a vulnerable demographic subgroup (African-American). Our approach not only finds patient subgroups with guidance of a clinically relevant target variable but also identifies and prioritizes risk factors by pursuing sparsity of the input variables and encouraging similarity among the input variables and between the input and target variable

An Archived Multi Objective Simulated Annealing Method to Discover Biclusters in Microarray Data

With the advent of microarray technology it has been possible to measure thousands of expression values of genes in a single experiment. Analysis of large scale geonomics data, notably gene expression, has initially focused on clustering methods. Recently, biclustering techniques were proposed for revealing submatrices showing unique patterns. Biclustering or simultaneous clustering of both genes and conditions is challenging particularly for the analysis of high-dimensional gene expression data in information retrieval, knowledge discovery, and data mining. In biclustering of microarray data, several objectives have to be optimized simultaneously and often these objectives are in conflict with each other. A multi objective model is very suitable for solving this problem. Our method proposes a algorithm which is based on multi objective Simulated Annealing for discovering biclusters in gene expression data. Experimental result in bench mark data base present a significant improvement in overlap among biclusters and coverage of elements in gene expression and quality of biclusters

Unsupervised Algorithms for Microarray Sample Stratification

The amount of data made available by microarrays gives researchers the opportunity to delve into the complexity of biological systems. However, the noisy and extremely high-dimensional nature of this kind of data poses significant challenges. Microarrays allow for the parallel measurement of thousands of molecular objects spanning different layers of interactions. In order to be able to discover hidden patterns, the most disparate analytical techniques have been proposed. Here, we describe the basic methodologies to approach the analysis of microarray datasets that focus on the task of (sub)group discovery.Peer reviewe

Pairwise gene GO-based measures for biclustering of high-dimensional expression data

Background: Biclustering algorithms search for groups of genes that share the same behavior under a subset of samples in gene expression data. Nowadays, the biological knowledge available in public repositories can be used to drive these algorithms to find biclusters composed of groups of genes functionally coherent. On the other hand, a distance among genes can be defined according to their information stored in Gene Ontology (GO). Gene pairwise GO semantic similarity measures report a value for each pair of genes which establishes their functional similarity. A scatter search-based algorithm that optimizes a merit function that integrates GO information is studied in this paper. This merit function uses a term that addresses the information through a GO measure. Results: The effect of two possible different gene pairwise GO measures on the performance of the algorithm is analyzed. Firstly, three well known yeast datasets with approximately one thousand of genes are studied. Secondly, a group of human datasets related to clinical data of cancer is also explored by the algorithm. Most of these data are high-dimensional datasets composed of a huge number of genes. The resultant biclusters reveal groups of genes linked by a same functionality when the search procedure is driven by one of the proposed GO measures. Furthermore, a qualitative biological study of a group of biclusters show their relevance from a cancer disease perspective. Conclusions: It can be concluded that the integration of biological information improves the performance of the biclustering process. The two different GO measures studied show an improvement in the results obtained for the yeast dataset. However, if datasets are composed of a huge number of genes, only one of them really improves the algorithm performance. This second case constitutes a clear option to explore interesting datasets from a clinical point of view.Ministerio de Economía y Competitividad TIN2014-55894-C2-

Discovering gene association networks by multi-objective evolutionary quantitative association rules

In the last decade, the interest in microarray technology has exponentially increased due to its ability to monitor the expression of thousands of genes simultaneously. The reconstruction of gene association networks from gene expression profiles is a relevant task and several statistical techniques have been proposed to build them. The problem lies in the process to discover which genes are more relevant and to identify the direct regulatory relationships among them. We developed a multi-objective evolutionary algorithm for mining quantitative association rules to deal with this problem. We applied our methodology named GarNet to a well-known microarray data of yeast cell cycle. The performance analysis of GarNet was organized in three steps similarly to the study performed by Gallo et al. GarNet outperformed the benchmark methods in most cases in terms of quality metrics of the networks, such as accuracy and precision, which were measured using YeastNet database as true network. Furthermore, the results were consistent with previous biological knowledge.Ministerio de Ciencia y Tecnología TIN2011-28956-C02-02Junta de Andalucía P11-TIC-752

Mining Structural Databases: An Evolutionary Multi-Objetive Conceptual Clustering Methodology

The increased availability of biological databases contain ing representations of complex objects permits access to vast amounts of data. In spite of the recent renewed interest in knowledge-discovery tech niques (or data mining), there is a dearth of data analysis methods in tended to facilitate understanding of the represented objects and related systems by their most representative features and those relationship de rived from these features (i.e., structural data). In this paper we propose a conceptual clustering methodology termed EMO-CC for Evolution ary Multi-Objective Conceptual Clustering that uses multi-objective and multi-modal optimization techniques based on Evolutionary Algorithms that uncover representative substructures from structural databases. Be sides, EMO-CC provides annotations of the uncovered substructures, and based on them, applies an unsupervised classification approach to retrieve new members of previously discovered substructures. We apply EMO-CC to the Gene Ontology database to recover interesting sub structures that describes problems from different points of view and use them to explain inmuno-inflammatory responses measured in terms of gene expression profiles derived from the analysis of longitudinal blood expression profiles of human volunteers treated with intravenous endo toxin compared to placebo