Innovative Hybridisation of Genetic Algorithms and Neural Networks in Detecting Marker Genes for Leukaemia Cancer

Methods for extracting marker genes that trigger the growth of cancerous cells from a high level of complexity microarrays are of much interest from the computing community. Through the identified genes, the pathology of cancerous cells can be revealed and early precaution can be taken to prevent further proliferation of cancerous cells. In this paper, we propose an innovative hybridised gene identification framework based on genetic algorithms and neural networks to identify marker genes for leukaemia disease. Our approach confirms that high classification accuracy does not ensure the optimal set of genes have been identified and our model delivers a more promising set of genes even with a lower classification accurac

Feature selection of microarray data using genetic algorithms and artificial neural networks

Microarrays, which allow for the measurement of thousands of gene expression levels in parallel, have created a wealth of data not previously available to biologists along with new computational challenges. Microarray studies are characterized by a low sample number and a large feature space with many features irrelevant to the problem being studied. This makes feature selection a necessary pre-processing step for many analyses, particularly classification. A Genetic Algorithm -Artificial Neural Network (ANN) wrapper approach is implemented to find the highest scoring set of features for an ANN classifier. Each generation relies on the performance of a set of features trained on an ANN for fitness evaluation. A publically-available leukemia microarray data set (Golub et al., 1999), consisting of 25 AML and 47 ALL Leukemia samples, each with 7129 features, is used to evaluate this approach. Results show an increased performance over Golub\u27s initial findings

Transcriptomics in Toxicogenomics, Part III: Data Modelling for Risk Assessment

Transcriptomics data are relevant to address a number of challenges in Toxicogenomics (TGx). After careful planning of exposure conditions and data preprocessing, the TGx data can be used in predictive toxicology, where more advanced modelling techniques are applied. The large volume of molecular profiles produced by omics-based technologies allows the development and application of artificial intelligence (AI) methods in TGx. Indeed, the publicly available omics datasets are constantly increasing together with a plethora of different methods that are made available to facilitate their analysis, interpretation and the generation of accurate and stable predictive models. In this review, we present the state-of-the-art of data modelling applied to transcriptomics data in TGx. We show how the benchmark dose (BMD) analysis can be applied to TGx data. We review read across and adverse outcome pathways (AOP) modelling methodologies. We discuss how network-based approaches can be successfully employed to clarify the mechanism of action (MOA) or specific biomarkers of exposure. We also describe the main AI methodologies applied to TGx data to create predictive classification and regression models and we address current challenges. Finally, we present a short description of deep learning (DL) and data integration methodologies applied in these contexts. Modelling of TGx data represents a valuable tool for more accurate chemical safety assessment. This review is the third part of a three-article series on Transcriptomics in Toxicogenomics

Consensus clustering and functional interpretation of gene-expression data

Microarray analysis using clustering algorithms can suffer from lack of inter-method consistency in assigning related gene-expression profiles to clusters. Obtaining a consensus set of clusters from a number of clustering methods should improve confidence in gene-expression analysis. Here we introduce consensus clustering, which provides such an advantage. When coupled with a statistically based gene functional analysis, our method allowed the identification of novel genes regulated by NFκB and the unfolded protein response in certain B-cell lymphomas

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

Gene regulatory network modelling with evolutionary algorithms -an integrative approach

Building models for gene regulation has been an important aim of Systems Biology over the past years, driven by the large amount of gene expression data that has become available. Models represent regulatory interactions between genes and transcription factors and can provide better understanding of biological processes, and means of simulating both natural and perturbed systems (e.g. those associated with disease). Gene regulatory network (GRN) quantitative modelling is still limited, however, due to data issues such as noise and restricted length of time series, typically used for GRN reverse engineering. These issues create an under-determination problem, with many models possibly fitting the data. However, large amounts of other types of biological data and knowledge are available, such as cross-platform measurements, knockout experiments, annotations, binding site affinities for transcription factors and so on. It has been postulated that integration of these can improve model quality obtained, by facilitating further filtering of possible models. However, integration is not straightforward, as the different types of data can provide contradictory information, and are intrinsically noisy, hence large scale integration has not been fully explored, to date. Here, we present an integrative parallel framework for GRN modelling, which employs evolutionary computation and different types of data to enhance model inference. Integration is performed at different levels. (i) An analysis of cross-platform integration of time series microarray data, discussing the effects on the resulting models and exploring crossplatform normalisation techniques, is presented. This shows that time-course data integration is possible, and results in models more robust to noise and parameter perturbation, as well as reduced noise over-fitting. (ii) Other types of measurements and knowledge, such as knock-out experiments, annotated transcription factors, binding site affinities and promoter sequences are integrated within the evolutionary framework to obtain more plausible GRN models. This is performed by customising initialisation, mutation and evaluation of candidate model solutions. The different data types are investigated and both qualitative and quantitative improvements are obtained. Results suggest that caution is needed in order to obtain improved models from combined data, and the case study presented here provides an example of how this can be achieved. Furthermore, (iii), RNA-seq data is studied in comparison to microarray experiments, to identify overlapping features and possibilities of integration within the framework. The extension of the framework to this data type is straightforward and qualitative improvements are obtained when combining predicted interactions from single-channel and RNA-seq datasets