Cancer adjuvant chemotherapy prediction model for non‐small cell lung cancer

Non‐small cell lung cancer (NSCLC) is the most popular and dangerous type of lung cancer. Adjuvant chemotherapy (ACT) is the main treatment after surgery resection to prevent the patient from cancer recurrence. However, ACT could be toxic and unhelpful in some cases. Therefore, it is highly desired in clinical applications to predict the treatment outcomes of chemotherapy. Conventional methods of predicting cancer treatment rely solely on histopathology and the results are not reliable in some cases. This study aims at building a predictive model to identify who needs ACT treatment and who should avoid it. To this end, the authors propose an innovative method to identify NSCLC‐related prognostic genes from microarray gene‐expression datasets. They also propose a new model using gene‐expression programming algorithm for ACT classification. The proposed model was evaluated on integrated microarray datasets from four institutes and compared with four representative methods: general regression neural network, decision tree, support vector machine and naive Bayes. Evaluation results demonstrated the effectiveness of the proposed model with accuracy 89.8% which is higher than other representative models. They obtained four probes (four genes) that can get good prediction results. These genes are 204891_s_at (LCK), 208893_s_at (DUSP6), 202454_s_at (ERBB3) and 201076_at (MMD).Inspec keywords: neural nets, regression analysis, decision trees, surgery, medical computing, cancer, cellular biophysics, lung, genetics, support vector machines, Bayes methods, biochemistryOther keywords: cancer ACT prediction model, nonsmall cell lung cancer, adjuvant chemotherapy, surgery resection, cancer recurrence, conventional methods, cancer treatment, microarray gene‐expression technology, NSCLC treatment, ACT treatment, NSCLC‐related prognostic genes, microarray gene‐expression datasets, gene‐expression programming algorithm, ACT classification, ACT information, integrated microarray datasets, representative models, survival time, general regression neural network, decision tree, support vector machine, naive Bayes     

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     

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     

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     

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     

Extended particle swarm optimisation method for folding protein on triangular lattice

In this study, the authors studied the protein structure prediction problem by the two‐dimensional hydrophobic–polar model on triangular lattice. Particularly the non‐compact conformation was modelled to fold the amino acid sequence into a relatively larger triangular lattice, which is more biologically realistic and significant than the compact conformation. Then protein structure prediction problem was abstracted to match amino acids to lattice points. Mathematically, the problem was formulated as an integer programming and they transformed the biological problem into an optimisation problem. To solve this problem, classical particle swarm optimisation algorithm was extended by the single point adjustment strategy. Compared with square lattice, conformations on triangular lattice are more flexible in several benchmark examples. They further compared the authors’ algorithm with hybrid of hill climbing and genetic algorithm. The results showed that their method was more effective in finding solution with lower energy and less running time.Inspec keywords: proteins, molecular biophysics, molecular configurations, particle swarm optimisation, bioinformaticsOther keywords: extended particle swarm optimisation method, triangular lattice, protein structure prediction problem, two‐dimensional hydrophobic–polar model, noncompact conformation, amino acid sequence, single point adjustment strategy, protein folding     

In silico discovery of significant pathways in colorectal cancer metastasis using a two‐stage optimisation approach

Accurate and reliable modelling of protein–protein interaction networks for complex diseases such as colorectal cancer can help better understand mechanism of diseases and potentially discover new drugs. Different machine learning methods such as empirical mode decomposition combined with least square support vector machine, and discrete Fourier transform have been widely utilised as a classifier and for automatic discovery of biomarkers for the diagnosis of the disease. The existing methods are, however, less efficient as they tend to ignore interaction with the classifier. In this study, the authors propose a two‐stage optimisation approach to effectively select biomarkers and discover interactions among them. At the first stage, particle swarm optimisation (PSO) and differential evolution (DE) are used to optimise parameters of support vector machine recursive feature elimination algorithm, and dynamic Bayesian network is then used to predict temporal relationship between biomarkers across two time points. Results show that 18 and 25 biomarkers selected by PSO and DE‐based approach, respectively, yields the same accuracy of 97.3% and F1‐score of 97.7 and 97.6%, respectively. The stratified analysis reveals that Alpha‐2‐HS‐glycoprotein was a dominant hub gene with multiple interactions to other genes including Fibrinogen alpha chain, which is also a potential biomarker for colorectal cancer.Inspec keywords: cancer, proteins, particle swarm optimisation, evolutionary computation, support vector machines, recursive functions, Bayes methods, genetics, molecular biophysics, medical computingOther keywords: colorectal cancer metastasis, two‐stage optimisation approach, protein–protein interaction networks, biomarkers, particle swarm optimisation, differential evolution, support vector machine recursive feature elimination, dynamic Bayesian network, stratified analysis, Alpha‐2‐HS‐glycoprotein, hub gene, Fibrinogen alpha chain     

Adaptive modelling of gene regulatory network using Bayesian information criterion‐guided sparse regression approach

Inferring gene regulatory networks (GRNs) from microarray expression data are an important but challenging issue in systems biology. In this study, the authors propose a Bayesian information criterion (BIC)‐guided sparse regression approach for GRN reconstruction. This approach can adaptively model GRNs by optimising the l ₁ ‐norm regularisation of sparse regression based on a modified version of BIC. The use of the regularisation strategy ensures the inferred GRNs to be as sparse as natural, while the modified BIC allows incorporating prior knowledge on expression regulation and thus avoids the overestimation of expression regulators as usual. Especially, the proposed method provides a clear interpretation of combinatorial regulations of gene expression by optimally extracting regulation coordination for a given target gene. Experimental results on both simulation data and real‐world microarray data demonstrate the competent performance of discovering regulatory relationships in GRN reconstruction.Inspec keywords: genetics, Bayes methods, genomics, regression analysis, inference mechanisms, bioinformaticsOther keywords: adaptive modelling, gene regulatory network, Bayesian information criterion‐guided sparse regression approach, GRN, microarray expression data, systems biology, GRN reconstruction, optimisation, l₁ ‐norm regularisation     

Parallel implementation of D‐Phylo algorithm for maximum likelihood clusters

This study explains a newly developed parallel algorithm for phylogenetic analysis of DNA sequences. The newly designed D‐Phylo is a more advanced algorithm for phylogenetic analysis using maximum likelihood approach. The D‐Phylo while misusing the seeking capacity of k ‐means keeps away from its real constraint of getting stuck at privately conserved motifs. The authors have tested the behaviour of D‐Phylo on Amazon Linux Amazon Machine Image(Hardware Virtual Machine)i2.4xlarge, six central processing unit, 122 GiB memory, 8 ×  800 Solid‐state drive Elastic Block Store volume, high network performance up to 15 processors for several real‐life datasets. Distributing the clusters evenly on all the processors provides us the capacity to accomplish a near direct speed if there should arise an occurrence of huge number of processors.Inspec keywords: parallel algorithms, Linux, pattern clustering, DNA, molecular biophysics, genetics, biology computingOther keywords: D‐Phylo algorithm parallel implementation, maximum likelihood clusters, DNA sequence phylogenetic analysis, Amazon Linux AMI, HVM, central processing unit, SSD, real‐life datasets, processors, high‐network performance     

Nutratherapeutics approach against cancer: tomato‐mediated synthesised gold nanoparticles

In this study, an eco‐friendly biosynthesis of stable gold nanoparticles (T‐GNPs) was carried out using different concentrations of tomato juice (nutraceuticals) as a reducing agent and tetrachloroauric acid as a metal precursor to explore their potential application in cancer therapeutics. The synthesis of T‐GNPs was monitored by UV‐visible absorption spectroscopy, which unveiled their formation by exhibiting the typical surface plasmon absorption maxima at 522 nm. The size of T‐GNPs was found to be 10.86 ± 0.6 nm. T‐GNPs were characterised by dynamic light scattering, zeta potential, transmission electron microscopy analysis and Fourier transform infrared spectroscopy. T‐GNPs were further investigated for their anti‐cancer activity against human lung carcinoma cell line (A ₅₄₉) and human cervical cancer cell line wherein the IC₅₀ values were found to be 0.286 and 0.200 mM, respectively. T‐GNPs inhibited the growth of cancer cells by generating ROS and inducing apoptosis. T‐GNPs were found highly effective by virtue of their size, metallic property and capping molecules. Thus, this study opens up the prospects of using nutraceutical (tomato juice) as nutratherapeutic agent (T‐GNPs) against critical diseases like lung cancer and cervical cancer.Inspec keywords: gold, nanoparticles, particle size, cancer, ultraviolet spectra, visible spectra, electrokinetic effects, transmission electron microscopy, Fourier transform infrared spectra, cellular biophysics, spectrochemical analysis, nanomedicine, nanofabricationOther keywords: tomato‐mediated synthesised gold nanoparticles, tomato juice, reducing agent, tetrachloroauric acid, cancer therapeutics, UV‐visible absorption spectroscopy, surface plasmon absorption, dynamic light scattering, zeta potential, transmission electron microscopy analysis, Fourier transform infrared spectroscopy, human lung carcinoma cell line, anticancer activity, human cervical cancer cell line, nutratherapeutic agent, lung cancer, Au     

Revisiting topological properties and models of protein–protein interaction networks from the perspective of dataset evolution

Protein–protein interaction (PPI) networks are crucial for organisms. Many research efforts have thus been devoted to the study on the topological properties and models of PPI networks. However, existing studies did not always report consistent results on the topological properties of PPI networks. Although a number of PPI network models have been introduced, yet in the literature there is no convincing conclusion on which model is best for describing PPI networks. This situation is primarily caused by the incompleteness of current PPI datasets. To solve this problem, in this study, the authors propose to revisit the topological properties and models of PPI networks from the perspective of PPI dataset evolution. Concretely, they used 12 PPI datasets of Arabidopsis thaliana and 10 PPI datasets of Saccharomyces cerevisiae from different Biological General Repository for Interaction Datasets (BioGRID) database versions, and compared the topological properties of these datasets and the fitting capabilities of five typical PPI network models over these datasets.Inspec keywords: proteins, molecular biophysics, microorganisms, cellular biophysicsOther keywords: topological properties, protein‐protein interaction networks, PPI network models, PPI dataset evolution, Arabidopsis thaliana, Saccharomyces cerevisiae, Biological General Repository‐for‐Interaction Datasets database, BioGRID database     

Synthesis,stability, and in vitro oral cancer cell toxicity of human serum albumin stabilised gold nanoflowers

Gold nanoflowers (GNFs) prepared by reduction of HAuCl₄ by ascorbic acid were capped with human serum albumin (HSA) by either electrostatic or covalent attachment to prevent their self‐aggregation. Measurement of surface plasmon resonance absorbance changes under different stress conditions showed that GNFs stabilised by covalent attachment of HSA were more stable than those stabilised by electrostatic attachment. Cytotoxicity of the covalently conjugated GNF was also studied in cultured human oral cancer cell lines by measuring the metabolic activity via 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay.Inspec keywords: proteins, molecular biophysics, biomedical materials, reduction (chemical), gold, cellular biophysics, nanofabrication, biochemistry, surface plasmon resonance, cancer, nanomedicine, materials preparation, nanostructured materialsOther keywords: Au, human serum albumin stabilised gold nanoflowers, cytotoxicity, in vitro oral cancer cell toxicity, stress conditions, surface plasmon resonance absorbance, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, self‐aggregation, covalent attachment, electrostatic attachment, ascorbic acid, cultured human oral cancer cell lines     

Non‐fragile reliable control synthesis of the sugarcane borer

This study considers the problem of non‐fragile reliable control synthesis for mathematical model of interaction between the sugarcane borer (Diatraea saccharalis) and its egg parasitoid Trichogramma galloi. In particular, the control could be substituted by periodic releases of a small population of natural enemies and hence it is important to propose the time‐varying controller in sugarcane borer. The main aim of this study is to design a state feedback non‐fragile (time‐varying) reliable controller such that the states of the sugarcane borer system reach the equilibrium point within the desired period. A novel approach is proposed to deal with the uncertain matrices which appear in non‐fragile reliable control. Finally, simulations based on sugarcane borer systems are conducted to illustrate the advantages and effectiveness of the proposed design technique. The result reveals that the proposed non‐fragile control provides good performance in spite of periodic releases of a small population of natural enemies occurs.Inspec keywords: microorganisms, plant diseases, biology computing, state feedback, biocontrol, control system synthesisOther keywords: nonfragile reliable control synthesis, sugarcane borer, mathematical model, Diatraea saccharalis, egg parasitoid, Trichogramma galloi, periodic releases, natural enemies, state feedback nonfragile time‐varying reliable controller, equilibrium point, design technique     

Emerging microfluidic devices for cancer cells/biomarkers manipulation and detection

Circulating tumour cells (CTCs) are active participants in the metastasis process and account for ∼90% of all cancer deaths. As CTCs are admixed with a very large amount of erythrocytes, leukocytes, and platelets in blood, CTCs are very rare, making their isolation, capture, and detection a major technological challenge. Microfluidic technologies have opened‐up new opportunities for the screening of blood samples and the detection of CTCs or other important cancer biomarker‐proteins. In this study, the authors have reviewed the most recent developments in microfluidic devices for cells/biomarkers manipulation and detection, focusing their attention on immunomagnetic‐affinity‐based devices, dielectrophoresis‐based devices, surface‐plasmon‐resonance microfluidic sensors, and quantum‐dots‐based sensors.Inspec keywords: microfluidics, bioMEMS, cancer, cellular biophysics, biomedical equipment, patient diagnosis, tumours, proteins, molecular biophysics, electrophoresis, surface plasmon resonance, quantum dotsOther keywords: quantum‐dot‐based sensors, surface‐plasmon‐resonance microfluidic sensors, dielectrophoresis‐based devices, immunomagnetic‐affinity‐based devices, cancer biomarker‐proteins, CTC detection, blood samples, microfluidic technology, platelets, leukocytes, leukocytes, erythrocytes, cancer deaths, metastasis process, circulating tumour cells, cancer cell‐biomarker detection, cancer cell‐biomarker manipulation, microfluidic devices     

Ensembled machine learning framework for drug sensitivity prediction

Drug sensitivity prediction is one of the critical tasks involved in drug designing and discovery. Recently several online databases and consortiums have contributed to providing open access to pharmacogenomic data. These databases have helped in developing computational approaches for drug sensitivity prediction. Cancer is a complex disease involving the heterogeneous behaviour of same tumour‐type patients towards the same kind of drug therapy. Several methods have been proposed in the literature to predict drug sensitivity. However, these methods are not efficient enough to predict drug sensitivity. The present study has proposed an ensemble learning framework for drug‐response prediction using a modified rotation forest. The proposed framework is further compared with three state‐of‐the‐art algorithms and two baseline methods using Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line Encyclopedia (CCLE) drug screens. The authors have also predicted missing drug response values in the data set using the proposed approach. The proposed approach outperforms other counterparts even though gene mutation data is not incorporated while designing the approach. An average mean square error of 3.14 and 0.404 is achieved using GDSC and CCLE drug screens, respectively. The obtained results show that the proposed framework has considerable potential to improve anti‐cancer drug response prediction.Inspec keywords: medical computing, molecular biophysics, genomics, genetics, learning (artificial intelligence), patient treatment, drugs, cellular biophysics, cancer, biology computing, tumours, diseasesOther keywords: ensembled machine learning framework, drug sensitivity prediction, drug therapy, ensemble learning framework, drug‐response prediction, Cancer Cell Line Encyclopedia drug screens, drug response values, CCLE drug screens, anti‐cancer drug response prediction