Lung cancer prediction from microarray data by gene expression programming

Lung cancer is a leading cause of cancer‐related death worldwide. The early diagnosis of cancer has demonstrated to be greatly helpful for curing the disease effectively. Microarray technology provides a promising approach of exploiting gene profiles for cancer diagnosis. In this study, the authors propose a gene expression programming (GEP)‐based model to predict lung cancer from microarray data. The authors use two gene selection methods to extract the significant lung cancer related genes, and accordingly propose different GEP‐based prediction models. Prediction performance evaluations and comparisons between the authors’ GEP models and three representative machine learning methods, support vector machine, multi‐layer perceptron and radial basis function neural network, were conducted thoroughly on real microarray lung cancer datasets. Reliability was assessed by the cross‐data set validation. The experimental results show that the GEP model using fewer feature genes outperformed other models in terms of accuracy, sensitivity, specificity and area under the receiver operating characteristic curve. It is concluded that GEP model is a better solution to lung cancer prediction problems.Inspec keywords: lung, cancer, medical diagnostic computing, patient diagnosis, genetic algorithms, feature selection, learning (artificial intelligence), support vector machines, multilayer perceptrons, radial basis function networks, reliability, sensitivity analysisOther keywords: lung cancer prediction, cancer‐related death, cancer diagnosis, gene profiles, gene expression programming‐based model, gene selection, GEP‐based prediction models, prediction performance evaluations, representative machine learning methods, support vector machine, multilayer perceptron, radial basis function neural network, real microarray lung cancer datasets, cross‐data set validation, reliability, receiver operating characteristic curve     

Prediction of NSCLC recurrence from microarray data with GEP

Lung cancer is one of the deadliest diseases in the world. Non‐small cell lung cancer (NSCLC) is the most common and dangerous type of lung cancer. Despite the fact that NSCLC is preventable and curable for some cases if diagnosed at early stages, the vast majority of patients are diagnosed very late. Furthermore, NSCLC usually recurs sometime after treatment. Therefore, it is of paramount importance to predict NSCLC recurrence, so that specific and suitable treatments can be sought. Nonetheless, conventional methods of predicting cancer recurrence rely solely on histopathology data and predictions are not reliable in many cases. The microarray gene expression (GE) technology provides a promising and reliable way to predict NSCLC recurrence by analysing the GE of sample cells. This study proposes a new model from GE programming to use microarray datasets for NSCLC recurrence prediction. To this end, the authors also propose a hybrid method to rank and select relevant prognostic genes that are related to NSCLC recurrence prediction. The proposed model was evaluated on real NSCLC microarray datasets and compared with other representational models. The results demonstrated the effectiveness of the proposed model.Inspec keywords: lung, cancer, lab‐on‐a‐chip, genetics, patient diagnosisOther keywords: NSCLC recurrence prediction, microarray data, GE programming, nonsmall cell lung cancer, cancer recurrence, histopathology data, microarray gene expression, prognostic genes     

Efficient heart disease prediction‐based on optimal feature selection using DFCSS and classification by improved Elman‐SFO

Prediction of cardiovascular disease (CVD) is a critical challenge in the area of clinical data analysis. In this study, an efficient heart disease prediction is developed based on optimal feature selection. Initially, the data pre‐processing process is performed using data cleaning, data transformation, missing values imputation, and data normalisation. Then the decision function‐based chaotic salp swarm (DFCSS) algorithm is used to select the optimal features in the feature selection process. Then the chosen attributes are given to the improved Elman neural network (IENN) for data classification. Here, the sailfish optimisation (SFO) algorithm is used to compute the optimal weight value of IENN. The combination of DFCSS–IENN‐based SFO (IESFO) algorithm effectively predicts heart disease. The proposed (DFCSS–IESFO) approach is implemented in the Python environment using two different datasets such as the University of California Irvine (UCI) Cleveland heart disease dataset and CVD dataset. The simulation results proved that the proposed scheme achieved a high‐classification accuracy of 98.7% for the CVD dataset and 98% for the UCI dataset compared to other classifiers, such as support vector machine, K‐nearest neighbour, Elman neural network, Gaussian Naive Bayes, logistic regression, random forest, and decision tree.Inspec keywords: cardiovascular system, medical diagnostic computing, feature extraction, regression analysis, data mining, learning (artificial intelligence), Bayes methods, neural nets, support vector machines, diseases, pattern classification, data handling, decision trees, cardiology, data analysis, feature selectionOther keywords: efficient heart disease prediction‐based, optimal feature selection, improved Elman‐SFO, cardiovascular disease, clinical data analysis, data pre‐processing process, data cleaning, data transformation, values imputation, data normalisation, decision function‐based chaotic salp swarm algorithm, optimal features, feature selection process, improved Elman neural network, data classification, sailfish optimisation algorithm, optimal weight value, DFCSS–IENN‐based SFO algorithm, DFCSS–IESFO, California Irvine Cleveland heart disease dataset, CVD dataset, high‐classification accuracy     

Latent factor analysis facilitates modelling of oncogenic genes for colon adenocarcinoma

Identification of oncogenic genes from a large sample number of genomic data is a challenge. In this study, a well‐established latent factor model, Bayesian factor and regression model, are applied to predict unknown colon cancer related genes from colon adenocarcinoma genomic data. Four important latent factors were addressed by the latent factor model, focusing on characterisation of heterogeneity of expression patterns of specific oncogenic genes by using microarray data of 174 colon cancer patients. Based on the fact that variables included in the same latent factor have some common characteristics and known cancer related genes in Online Mendelian Inheritance in Man, the authors found that the four latent factors can be employed to predict unknown colon cancer related genes that were never reported in the literature. The authors validated 15 identified genes by checking their somatic mutations of the same patients from DNA sequencing data.Inspec keywords: Bayes methods, biological organs, cancer, DNA, genetics, genomics, lab‐on‐a‐chip, medical diagnostic computing, molecular biophysics, physiological models, regression analysisOther keywords: latent factor analysis, oncogenic genes, colon adenocarcinoma, genomic data, Bayesian factor, colon cancer related genes, heterogeneity, expression patterns, DNA microarray data, Online Mendelian Inheritance in Man, somatic mutations, DNA sequencing data     

Mining conditions specific hub genes from RNA‐Seq gene‐expression data via biclustering and their application to drug discovery

Gene‐expression data is being widely used for various clinical research. It represents expression levels of thousands of genes across the various experimental conditions simultaneously. Mining conditions specific hub genes from gene‐expression data is a challenging task. Conditions specific hub genes signify the functional behaviour of bicluster across the subset of conditions and can act as prognostic or diagnostic markers of the diseases. In this study, the authors have introduced a new approach for identifying conditions specific hub genes from the RNA‐Seq data using a biclustering algorithm. In the proposed approach, efficient ‘runibic’ biclustering algorithm, the concept of gene co‐expression network and concept of protein–protein interaction network have been used for getting better performance. The result shows that the proposed approach extracts biologically significant conditions specific hub genes which play an important role in various biological processes and pathways. These conditions specific hub genes can be used as prognostic or diagnostic biomarkers. Conditions specific hub genes will be helpful to reduce the analysis time and increase the accuracy of further research. Also, they summarised application of the proposed approach to the drug discovery process.Inspec keywords: proteins, data mining, cellular biophysics, drugs, genetics, diseases, RNA, medical computing, biology computing, molecular biophysicsOther keywords: experimental conditions, mining conditions specific hub genes, identifying conditions specific hub genes, RNA‐Seq data, gene co‐expression network, significant conditions specific hub genes, RNA‐Seq gene‐expression data     

Identification of self‐regulatory network motifs in reverse engineering gene regulatory networks using microarray gene expression data

Gene Regulatory Networks (GRNs) are reconstructed from the microarray gene expression data through diversified computational approaches. This process ensues in symmetric and diagonal interaction of gene pairs that cannot be modelled as direct activation, inhibition, and self‐regulatory interactions. The values of gene co‐expressions could help in identifying co‐regulations among them. The proposed approach aims at computing the differences in variances of co‐expressed genes rather than computing differences in values of mean expressions across experimental conditions. It adopts multivariate co‐variances using principal component analysis (PCA) to predict an asymmetric and non‐diagonal gene interaction matrix, to select only those gene pair interactions that exhibit the maximum variances in gene regulatory expressions. The asymmetric gene regulatory interactions help in identifying the controlling regulatory agents, thus lowering the false positive rate by minimizing the connections between previously unlinked network components. The experimental results on real as well as in silico datasets including time‐series RTX therapy, Arabidopsis thaliana, DREAM‐3, and DREAM‐8 datasets, in comparison with existing state‐of‐the‐art approaches demonstrated the enhanced performance of the proposed approach for predicting positive and negative feedback loops and self‐regulatory interactions. The generated GRNs hold the potential in determining the real nature of gene pair regulatory interactions.Inspec keywords: molecular biophysics, principal component analysis, genetics, biology computing, reverse engineeringOther keywords: controlling regulatory agents, interacting genes, unlinked network components, self‐regulatory interactions, gene pair regulatory interactions, self‐regulatory network motifs, reverse engineering gene regulatory networks, microarray gene expression data, diversified computational approaches, symmetric interaction, diagonal interaction, gene pairs, gene co‐expressions, co‐expressed genes, mean expressions, gene regulatory expressions, asymmetric gene regulatory interactions     

Identification of specific microRNA–messenger RNA regulation pairs in four subtypes of breast cancer

Four subtypes of breast cancer, luminal A, luminal B, basal‐like, human epidermal growth factor receptor‐enriched, have been identified based on gene expression profiles of human tumours. The goal of this study is to find whether the same groups'' genes would exhibit different networks among the four subtypes. Differential expressed genes between each of the four subtypes and the normal samples were identified. The overlaps between the four groups of differentially expressed genes were used to construct regulations networks for each of the four subtypes. Univariate and multivariate Cox regressions were employed to test the genes in the four regulation networks. This study demonstrated that the common genes in four subtypes showed different regulation. Also, the hsa‐miR‐182 and decorin pair performs different functions among the four subtypes of breast cancer. The result indicated that heterogeneity of breast cancer is not only reflected in the different expression patterns among different genes, but also in the different regulatory networks of the same group of genes.Inspec keywords: genetics, cellular biophysics, tumours, molecular biophysics, RNA, biochemistry, cancer, proteins, biology computingOther keywords: decorin pair performs different functions, breast cancer heterogeneity, regulatory networks, specific microRNA–messenger, regulation pairs, human epidermal growth factor receptor, gene expression profiles, differentially expressed genes, regulations networks, hsa‐miR‐182, decorin pair, human tumours     

Cancers classification based on deep neural networks and emotional learning approach

In the present era, enormous factors contribute to causing cancer. So cancer classification cannot rely only on doctor''s thoughts. As a result, intelligent algorithms concerning doctor''s help are inevitable. Therefore, the authors are motivated to suggest a novel algorithm to classify three cancer datasets; colon, ALL‐AML, and leukaemia cancers. Their proposed algorithm is based on the deep neural network and emotional learning process. First of all, by applying the principal component analysis, they had a feature reduction. Then, they used deep neural as a feature extraction. Then, they implemented different classifiers; multi‐layer perceptron, support vector machine (SVM), decision tree, and Gaussian mixture model. In the end, because in the real world, especially when working on systems biology, unpredictable events, and uncertainties are undeniable, the robustness of their model against uncertainties is important. So they added Gaussian noise to the input features of the first encoder in each dataset, then, they applied the stacked denoising method. Experimental results disclosed that, generally, using emotional learning increased the accuracy. In addition, the highest accuracy was gained by SVM, 91.66, 92.27, and 96.56% for colon, ALL‐AML, and leukaemia, respectively. However, GMM led to the lowest accuracy. The best accuracy gained by GMM was 60%.Inspec keywords: cancer, learning (artificial intelligence), principal component analysis, multilayer perceptrons, feature extraction, support vector machines, pattern classification, Gaussian processes, decision trees, Gaussian noise, medical computingOther keywords: colon cancer, Gaussian noise, stacked denoising method, SVM, support vector machine, emotional learning process, cancer datasets, intelligent algorithms, cancer classification, ALL‐AML, input features, Gaussian mixture model, decision tree, multilayer perceptron, feature extraction, feature reduction, principal component analysis, deep neural network, leukaemia cancers     

In silico identification of potential targets and drugs for non‐small cell lung cancer

Lung cancer is one of the leading causes of death in both the USA and Taiwan, and it is thought that the cause of cancer could be because of the gain of function of an oncoprotein or the loss of function of a tumour suppressor protein. Consequently, these proteins are potential targets for drugs. In this study, differentially expressed genes are identified, via an expression dataset generated from lung adenocarcinoma tumour and adjacent non‐tumour tissues. This study has integrated many complementary resources, that is, microarray, protein‐protein interaction and protein complex. After constructing the lung cancer protein‐protein interaction network (PPIN), the authors performed graph theory analysis of PPIN. Highly dense modules are identified, which are potential cancer‐associated protein complexes. Up‐ and down‐regulated communities were used as queries to perform functional enrichment analysis. Enriched biological processes and pathways are determined. These sets of up‐ and down‐regulated genes were submitted to the Connectivity Map web resource to identify potential drugs. The authors'' findings suggested that eight drugs from DrugBank and three drugs from NCBI can potentially reverse certain up‐ and down‐regulated genes'' expression. In conclusion, this study provides a systematic strategy to discover potential drugs and target genes for lung cancer.Inspec keywords: cellular biophysics, lung, cancer, drugs, genetics, tumours, lab‐on‐a‐chip, proteins, molecular biophysics, graph theory, query processing, medical computingOther keywords: down‐regulated gene expression, up‐regulated gene expression, potential target genes, DrugBank, potential drugs, connectivity map Web resource, biological processes, functional enrichment analysis, up‐regulated communities, down‐regulated communities, cancer‐associated protein complexes, k‐communities, highly‐dense modules, PPIN, graph theory analysis, lung cancer protein‐protein interaction network, MIPS, BioGrid, ArrayExpress, microarray, nontumour tissues, human lung adenocarcinoma tumour, bioconductor package, tumour suppressor protein, oncoprotein, nonsmall cell lung cancer, in silico identification     

Multi‐threshold and multi‐input DNA logic design style for profiling the microRNA biomarkers of real cancers

Early detection of cancer is very critical because it can reduce the treatment risk and cost. MicroRNAs (miRNAs) have been introduced in recent years as an efficient class of biomarkers for cancer early detection. Now, real‐time polymerase chain reaction has been used to profile the miRNA expression, which is costly, time consuming and low accuracy. Most recently, DNA logic gates are used to detect the miRNA expression level that is more accurate and faster than previous methods. The DNA‐based logic gates face with serious challenges such as the large complexity and low scalability. In this study, the authors proposed a methodology to design multi‐threshold and multi‐input DNA‐based logic gates in response to specific miRNA inputs in live mammalian cells. The proposed design style can simultaneously recognise multiple miRNAs with different rising and falling thresholds. The design style has been evaluated on the lung cancer biomarkers and the experimental results show the efficiency of the proposed method in terms of accuracy, efficiency and speed.Inspec keywords: DNA, logic design, biocomputing, RNA, molecular biophysics, logic gates, lung, genetics, cellular biophysics, cancer, biology computing, enzymes, biosensorsOther keywords: falling thresholds, specific miRNA inputs, multiinput DNA‐based logic gates, low scalability, DNA‐based logic gates face, miRNA expression level, DNA logic gates, low accuracy, time consuming, real‐time polymerase chain reaction, cancer early detection, treatment risk, cancers, microRNA biomarkers, multiinput DNA logic design style, multithreshold, lung cancer biomarkers     

Efficient prediction of drug–drug interaction using deep learning models

A drug–drug interaction or drug synergy is extensively utilised for cancer treatment. However, prediction of drug–drug interaction is defined as an ill‐posed problem, because manual testing is only implementable on small group of drugs. Predicting the drug–drug interaction score has been a popular research topic recently. Recently many machine learning models have proposed in the literature to predict the drug–drug interaction score efficiently. However, these models suffer from the over‐fitting issue. Therefore, these models are not so‐effective for predicting the drug–drug interaction score. In this work, an integrated convolutional mixture density recurrent neural network is proposed and implemented. The proposed model integrates convolutional neural networks, recurrent neural networks and mixture density networks. Extensive comparative analysis reveals that the proposed model significantly outperforms the competitive models.Inspec keywords: cancer, learning (artificial intelligence), drugs, recurrent neural nets, convolutional neural nets, drug delivery systemsOther keywords: drug synergy, drug–drug interaction score, drug–drug interaction prediction, deep learning, cancer treatment, machine learning, convolutional mixture density recurrent neural network     

Fold change based approach for identification of significant network markers in breast,lung and prostate cancer

Cancer belongs to a class of highly aggressive diseases and a leading cause of death in the world. With more than 100 types of cancers, breast, lung and prostate cancer remain to be the most common types. To identify essential network markers (NMs) and therapeutic targets in these cancers, the authors present a novel approach which uses gene expression data from microarray and RNA‐seq platforms and utilises the results from this data to evaluate protein–protein interaction (PPI) network. Differentially expressed genes (DEGs) are extracted from microarray data using three different statistical methods in R, to produce a consistent set of genes. Also, DEGs are extracted from RNA‐seq data for the same three cancer types. DEG sets found to be common in both platforms are obtained at three fold change (FC) cut‐off levels to accurately identify the level of change in expression of these genes in all three cancers. A cancer network is built using PPI data characterising gene sets at log‐FC (LFC)>1, LFC>1.5 and LFC>2, and interconnection between principal hub nodes of these networks is observed. Resulting network of hubs at three FC levels highlights prime NMs with high confidence in multiple cancers as validated by Gene Ontology functional enrichment and maximal complete subgraphs from CFinder.Inspec keywords: cancer, proteins, RNA, bioinformatics, statistical analysis, genetics, molecular biophysics, ontologies (artificial intelligence), lungOther keywords: cancer network, PPI data, gene sets, multiple cancers, Gene Ontology functional enrichment, prostate cancer, gene expression data, RNA‐seq platforms, protein–protein interaction network, DEG, microarray data, RNA‐seq data, cancer types, lung cancer, diseases, breast cancer, network markers, differentially expressed genes, fold change based approach, CFinder, statistical methods     

Pseudo‐spectral method for controlling the drug dosage in cancer

A mixed chemotherapy–immunotherapy treatment protocol is developed for cancer treatment. Chemotherapy pushes the trajectory of the system towards the desired equilibrium point, and then immunotherapy alters the dynamics of the system by affecting the parameters of the system. A co‐existing cancerous equilibrium point is considered as the desired equilibrium point instead of the tumour‐free equilibrium. Chemotherapy protocol is derived using the pseudo‐spectral (PS) controller due to its high convergence rate and simple implementation structure. Thus, one of the contributions of this study is simplifying the design procedure and reducing the controller computational load in comparison with Lyapunov‐based controllers. In this method, an infinite‐horizon optimal control problem is proposed for a non‐linear cancer model. Then, the infinite‐horizon optimal control of cancer is transformed into a non‐linear programming problem. The efficient Legendre PS scheme is suggested to solve the proposed problem. Then, the dynamics of the system is modified by immunotherapy is another contribution. To restrict the upper limit of the chemo‐drug dose based on the age of the patients, a Mamdani fuzzy system is designed, which is not present yet. Simulation results on four different dynamics cases how the efficiency of the proposed treatment strategy.Inspec keywords: patient treatment, cancer, convergence, linear programming, optimal control, nonlinear programming, nonlinear control systems, Lyapunov methods, drugs, tumoursOther keywords: nonlinear programming problem, efficient Legendre PS scheme, chemo‐drug dose, Mamdani fuzzy system, treatment strategy, pseudospectral method, drug dosage, mixed chemotherapy–immunotherapy treatment protocol, cancer treatment, desired equilibrium point, immunotherapy alters, cancerous equilibrium point, tumour‐free equilibrium, chemotherapy protocol, pseudospectral controller, high convergence rate, simple implementation structure, controller computational load, Lyapunov‐based controllers, infinite‐horizon optimal control problem, nonlinear cancer model     

Chaotic emperor penguin optimised extreme learning machine for microarray cancer classification

Microarray technology plays a significant role in cancer classification, where a large number of genes and samples are simultaneously analysed. For the efficient analysis of the microarray data, there is a great demand for the development of intelligent techniques. In this article, the authors propose a novel hybrid technique employing Fisher criterion, ReliefF, and extreme learning machine (ELM) based on the principle of chaotic emperor penguin optimisation algorithm (CEPO). EPO is a recently developed metaheuristic method. In the proposed method, initially, Fisher score and ReliefF are independently used as filters for relevant gene selection. Further, a novel population‐based metaheuristic, namely, CEPO was proposed to pre‐train the ELM by selecting the optimal input weights and hidden biases. The authors have successfully conducted experiments on seven well‐known data sets. To evaluate the effectiveness, the proposed method is compared with original EPO, genetic algorithm, and particle swarm optimisation‐based ELM along with other state‐of‐the‐art techniques. The experimental results show that the proposed framework achieves better accuracy as compared to the state‐of‐the‐art schemes. The efficacy of the proposed method is demonstrated in terms of accuracy, sensitivity, specificity, and F‐measure.Inspec keywords: genetic algorithms, pattern classification, biology computing, cancer, learning (artificial intelligence), search problems, particle swarm optimisationOther keywords: optimal input weights, data sets, original EPO, genetic algorithm, particle swarm optimisation‐based ELM, microarray cancer classification, microarray technology, microarray data, intelligent techniques, Fisher criterion, ReliefF, chaotic emperor penguin optimisation algorithm, CEPO, recently developed metaheuristic method, Fisher score, relevant gene selection, population‐based, chaotic penguin optimised extreme learning machine, F     

Gaussian graphical model for identifying significantly responsive regulatory networks from time course high‐throughput data

With rapid accumulation of functional relationships between biological molecules, knowledge‐based networks have been constructed and stocked in many databases. These networks provide curated and comprehensive information for functional linkages among genes and proteins, whereas their activities are highly related with specific phenotypes and conditions. To evaluate a knowledge‐based network in a specific condition, the consistency between its structure and conditionally specific gene expression profiling data are an important criterion. In this study, the authors propose a Gaussian graphical model to evaluate the documented regulatory networks by the consistency between network architectures and time course gene expression profiles. They derive a dynamic Bayesian network model to evaluate gene regulatory networks in both simulated and true time course microarray data. The regulatory networks are evaluated by matching network structure with gene expression to achieve consistency measurement. To demonstrate the effectiveness of the authors method, they identify significant regulatory networks in response to the time course of circadian rhythm. The knowledge‐based networks are screened and ranked by their structural consistencies with dynamic gene expression profiling.Inspec keywords: Bayes methods, biology computing, circadian rhythms, Gaussian processes, genetics, genomics, graphs, molecular biophysics, proteinsOther keywords: Gaussian graphical model, responsive regulatory networks, time course high‐throughput data, biological molecules, dynamic gene expression proflling, circadian rhythm, consistency measurement, matching network structure, simulated time course microarray data, true time course microarray data, dynamic Bayesian network model, time course gene expression proflles, network architectures, documented regulatory networks, speciflc gene expression proflling data, phenotypes, proteins, functional linkages, databases, knowledge‐based networks