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

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

A cDNA Microarray Gene Expression Data Classifier for Clinical Diagnostics Based on Graph Theory

Despite great advances in discovering cancer molecular profiles, the proper application of microarray technology to routine clinical diagnostics is still a challenge. Current practices in the classification of microarrays' data show two main limitations: the reliability of the training data sets used to build the classifiers, and the classifiers' performances, especially when the sample to be classified does not belong to any of the available classes. In this case, state-of-the-art algorithms usually produce a high rate of false positives that, in real diagnostic applications, are unacceptable. To address this problem, this paper presents a new cDNA microarray data classification algorithm based on graph theory and is able to overcome most of the limitations of known classification methodologies. The classifier works by analyzing gene expression data organized in an innovative data structure based on graphs, where vertices correspond to genes and edges to gene expression relationships. To demonstrate the novelty of the proposed approach, the authors present an experimental performance comparison between the proposed classifier and several state-of-the-art classification algorithm

Identification of a selective G1-phase benzimidazolone inhibitor by a senescence-targeted virtual screen using artificial neural networks

Cellular senescence is a barrier to tumorigenesis in normal cells and tumour cells undergo senescence responses to genotoxic stimuli, which is a potential target phenotype for cancer therapy. However, in this setting, mixed-mode responses are common with apoptosis the dominant effect. Hence, more selective senescence inducers are required. Here we report a machine learning-based in silico screen to identify potential senescence agonists. We built profiles of differentially affected biological process networks from expression data obtained under induced telomere dysfunction conditions in colorectal cancer cells and matched these to a panel of 17 protein targets with confirmatory screening data in PubChem. We trained a neural network using 3517 compounds identified as active or inactive against these targets. The resulting classification model was used to screen a virtual library of ~2M lead-like compounds. 147 virtual hits were acquired for validation in growth inhibition and senescence-associated β-galactosidase (SA-β-gal) assays. Among the found hits a benzimidazolone compound, CB-20903630, had low micromolar IC50 for growth inhibition of HCT116 cells and selectively induced SA-β-gal activity in the entire treated cell population without cytotoxicity or apoptosis induction. Growth suppression was mediated by G1 blockade involving increased p21 expression and suppressed cyclin B1, CDK1 and CDC25C. Additionally, the compound inhibited growth of multicellular spheroids and caused severe retardation of population kinetics in long term treatments. Preliminary structure-activity and structure clustering analyses are reported and expression analysis of CB-20903630 against other cell cycle suppressor compounds suggested a PI3K/AKT-inhibitor-like profile in normal cells, with different pathways affected in cancer cells

Non-uniform Feature Sampling for Decision Tree Ensembles

We study the effectiveness of non-uniform randomized feature selection in decision tree classification. We experimentally evaluate two feature selection methodologies, based on information extracted from the provided dataset: $(i)$ \emph{leverage scores-based} and $(ii)$ \emph{norm-based} feature selection. Experimental evaluation of the proposed feature selection techniques indicate that such approaches might be more effective compared to naive uniform feature selection and moreover having comparable performance to the random forest algorithm [3]Comment: 7 pages, 7 figures, 1 tabl

Toward a General-Purpose Heterogeneous Ensemble for Pattern Classification

We perform an extensive study of the performance of different classification approaches on twenty-five datasets (fourteen image datasets and eleven UCI data mining datasets). The aim is to find General-Purpose (GP) heterogeneous ensembles (requiring little to no parameter tuning) that perform competitively across multiple datasets. The state-of-the-art classifiers examined in this study include the support vector machine, Gaussian process classifiers, random subspace of adaboost, random subspace of rotation boosting, and deep learning classifiers. We demonstrate that a heterogeneous ensemble based on the simple fusion by sum rule of different classifiers performs consistently well across all twenty-five datasets. The most important result of our investigation is demonstrating that some very recent approaches, including the heterogeneous ensemble we propose in this paper, are capable of outperforming an SVM classifier (implemented with LibSVM), even when both kernel selection and SVM parameters are carefully tuned for each dataset