Evolutionary design of decision-tree algorithms tailored to microarray gene expression data sets

Decision-tree induction algorithms are widely used in machine learning applications in which the goal is to extract knowledge from data and present it in a graphically intuitive way. The most successful strategy for inducing decision trees is the greedy top-down recursive approach, which has been continuously improved by researchers over the past 40 years. In this paper, we propose a paradigm shift in the research of decision trees: instead of proposing a new manually designed method for inducing decision trees, we propose automatically designing decision-tree induction algorithms tailored to a specific type of classification data set (or application domain). Following recent breakthroughs in the automatic design of machine learning algorithms, we propose a hyper-heuristic evolutionary algorithm called hyper-heuristic evolutionary algorithm for designing decision-tree algorithms (HEAD-DT) that evolves design components of top-down decision-tree induction algorithms. By the end of the evolution, we expect HEAD-DT to generate a new and possibly better decision-tree algorithm for a given application domain. We perform extensive experiments in 35 real-world microarray gene expression data sets to assess the performance of HEAD-DT, and compare it with very well known decision-tree algorithms such as C4.5, CART, and REPTree. Results show that HEAD-DT is capable of generating algorithms that significantly outperform the baseline manually designed decision-tree algorithms regarding predictive accuracy and F-measure

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 Overview of the Use of Neural Networks for Data Mining Tasks

In the recent years the area of data mining has experienced a considerable demand for technologies that extract knowledge from large and complex data sources. There is a substantial commercial interest as well as research investigations in the area that aim to develop new and improved approaches for extracting information, relationships, and patterns from datasets. Artificial Neural Networks (NN) are popular biologically inspired intelligent methodologies, whose classification, prediction and pattern recognition capabilities have been utilised successfully in many areas, including science, engineering, medicine, business, banking, telecommunication, and many other fields. This paper highlights from a data mining perspective the implementation of NN, using supervised and unsupervised learning, for pattern recognition, classification, prediction and cluster analysis, and focuses the discussion on their usage in bioinformatics and financial data analysis tasks

New Trends in Artificial Intelligence: Applications of Particle Swarm Optimization in Biomedical Problems

Optimization is a process to discover the most effective element or solution from a set of all possible resources or solutions. Currently, there are various biological problems such as extending from biomolecule structure prediction to drug discovery that can be elevated by opting standard protocol for optimization. Particle swarm optimization (PSO) process, purposed by Dr. Eberhart and Dr. Kennedy in 1995, is solely based on population stochastic optimization technique. This method was designed by the researchers after inspired by social behavior of flocking bird or schooling fishes. This method shares numerous resemblances with the evolutionary computation procedures such as genetic algorithms (GA). Since, PSO algorithms is easy process to subject with minor adjustment of a few restrictions, it has gained more attention or advantages over other population based algorithms. Hence, PSO algorithms is widely used in various research fields like ranging from artificial neural network training to other areas where GA can be used in the system

Identifying potential circulating miRNA biomarkers for the diagnosis and prediction of ovarian cancer using machine-learning approach: application of Boruta

Introduction: In gynecologic oncology, ovarian cancer is a great clinical challenge. Because of the lack of typical symptoms and effective biomarkers for noninvasive screening, most patients develop advanced-stage ovarian cancer by the time of diagnosis. MicroRNAs (miRNAs) are a type of non-coding RNA molecule that has been linked to human cancers. Specifying diagnostic biomarkers to determine non-cancer and cancer samples is difficult.Methods: By using Boruta, a novel random forest-based feature selection in the machine-learning techniques, we aimed to identify biomarkers associated with ovarian cancer using cancerous and non-cancer samples from the Gene Expression Omnibus (GEO) database: GSE106817. In this study, we used two independent GEO data sets as external validation, including GSE113486 and GSE113740. We utilized five state-of-the-art machine-learning algorithms for classification: logistic regression, random forest, decision trees, artificial neural networks, and XGBoost.Results: Four models discovered in GSE113486 had an AUC of 100%, three in GSE113740 with AUC of over 94%, and four in GSE113486 with AUC of over 94%. We identified 10 miRNAs to distinguish ovarian cancer cases from normal controls: hsa-miR-1290, hsa-miR-1233-5p, hsa-miR-1914-5p, hsa-miR-1469, hsa-miR-4675, hsa-miR-1228-5p, hsa-miR-3184-5p, hsa-miR-6784-5p, hsa-miR-6800-5p, and hsa-miR-5100. Our findings suggest that miRNAs could be used as possible biomarkers for ovarian cancer screening, for possible intervention

Analysing functional genomics data using novel ensemble, consensus and data fusion techniques

Motivation: A rapid technological development in the biosciences and in computer science in the last decade has enabled the analysis of high-dimensional biological datasets on standard desktop computers. However, in spite of these technical advances, common properties of the new high-throughput experimental data, like small sample sizes in relation to the number of features, high noise levels and outliers, also pose novel challenges. Ensemble and consensus machine learning techniques and data integration methods can alleviate these issues, but often provide overly complex models which lack generalization capability and interpretability. The goal of this thesis was therefore to develop new approaches to combine algorithms and large-scale biological datasets, including novel approaches to integrate analysis types from different domains (e.g. statistics, topological network analysis, machine learning and text mining), to exploit their synergies in a manner that provides compact and interpretable models for inferring new biological knowledge. Main results: The main contributions of the doctoral project are new ensemble, consensus and cross-domain bioinformatics algorithms, and new analysis pipelines combining these techniques within a general framework. This framework is designed to enable the integrative analysis of both large- scale gene and protein expression data (including the tools ArrayMining, Top-scoring pathway pairs and RNAnalyze) and general gene and protein sets (including the tools TopoGSA , EnrichNet and PathExpand), by combining algorithms for different statistical learning tasks (feature selection, classification and clustering) in a modular fashion. Ensemble and consensus analysis techniques employed within the modules are redesigned such that the compactness and interpretability of the resulting models is optimized in addition to the predictive accuracy and robustness. The framework was applied to real-word biomedical problems, with a focus on cancer biology, providing the following main results: (1) The identification of a novel tumour marker gene in collaboration with the Nottingham Queens Medical Centre, facilitating the distinction between two clinically important breast cancer subtypes (framework tool: ArrayMining) (2) The prediction of novel candidate disease genes for Alzheimer’s disease and pancreatic cancer using an integrative analysis of cellular pathway definitions and protein interaction data (framework tool: PathExpand, collaboration with the Spanish National Cancer Centre) (3) The prioritization of associations between disease-related processes and other cellular pathways using a new rule-based classification method integrating gene expression data and pathway definitions (framework tool: Top-scoring pathway pairs) (4) The discovery of topological similarities between differentially expressed genes in cancers and cellular pathway definitions mapped to a molecular interaction network (framework tool: TopoGSA, collaboration with the Spanish National Cancer Centre) In summary, the framework combines the synergies of multiple cross-domain analysis techniques within a single easy-to-use software and has provided new biological insights in a wide variety of practical settings

Transcription factor binding specificity and occupancy : elucidation, modelling and evaluation

The major contributions of this thesis are addressing the need for an objective quality evaluation of a transcription factor binding model, demonstrating the value of the tools developed to this end and elucidating how in vitro and in vivo information can be utilized to improve TF binding specificity models. Accurate elucidation of TF binding specificity remains an ongoing challenge in gene regulatory research. Several in vitro and in vivo experimental techniques have been developed followed by a proliferation of algorithms, and ultimately, the binding models. This increase led to a choice problem for the end users: which tools to use, and which is the most accurate model for a given TF? Therefore, the first section of this thesis investigates the motif assessment problem: how scoring functions, choice and processing of benchmark data, and statistics used in evaluation affect motif ranking. This analysis revealed that TF motif quality assessment requires a systematic comparative analysis, and that scoring functions used have a TF-specific effect on motif ranking. These results advised the design of a Motif Assessment and Ranking Suite MARS, supported by PBM and ChIP-seq benchmark data and an extensive collection of PWM motifs. MARS implements consistency, enrichment, and scoring and classification-based motif evaluation algorithms. Transcription factor binding is also influenced and determined by contextual factors: chromatin accessibility, competition or cooperation with other TFs, cell line or condition specificity, binding locality (e.g. proximity to transcription start sites) and the shape of the binding site (DNA-shape). In vitro techniques do not capture such context; therefore, this thesis also combines PBM and DNase-seq data using a comparative k-mer enrichment approach that compares open chromatin with genome-wide prevalence, achieving a modest performance improvement when benchmarked on ChIP-seq data. Finally, since statistical and probabilistic methods cannot capture all the information that determine binding, a machine learning approach (XGBooost) was implemented to investigate how the features contribute to TF specificity and occupancy. This combinatorial approach improves the predictive ability of TF specificity models with the most predictive feature being chromatin accessibility, while the DNA-shape and conservation information all significantly improve on the baseline model of k-mer and DNase data. The results and the tools introduced in this thesis are useful for systematic comparative analysis (via MARS) and a combinatorial approach to modelling TF binding specificity, including appropriate feature engineering practices for machine learning modelling