CDHu40: a novel marker gene set of neuroendocrine prostate cancer (NEPC).

Prostate cancer (PCa) is the most prevalent cancer affecting American men. Castration-resistant prostate cancer (CRPC) can emerge during hormone therapy for PCa, manifesting with elevated serum prostate-specific antigen (PSA) levels, continued disease progression, and/or metastasis to the new sites, resulting in a poor prognosis. A subset of CRPC patients shows a neuroendocrine (NE) phenotype, signifying reduced or no reliance on androgen receptor (AR) signaling and a particularly unfavorable prognosis. In this study, we incorporated computational approaches based on both gene expression profiles and protein-protein interaction (PPI) networks. We identified 500 potential marker genes, which are significantly enriched in cell cycle and neuronal processes. The top 40 candidates, collectively named as CDHu40, demonstrated superior performance in distinguishing NE prostate cancer (NEPC) and non-NEPC samples based on gene expression profiles compared to other published marker sets. Notably, some novel marker genes in CDHu40, absent in the other marker sets, have been reported to be associated with NEPC in the literature, such as DDC, FOLH1, BEX1, MAST1, and CACNA1A. Importantly, elevated CDHu40 scores derived from our predictive model showed a robust correlation with unfavorable survival outcomes in patients, indicating the potential of the CDHu40 score as a promising indicator for predicting the survival prognosis of those patients with the NE phenotype. Motif enrichment analysis on the top candidates suggests that REST and E2F6 may serve as key regulators in the NEPC progression. Significance: our study integrates gene expression variances in multiple NEPC studies and protein-protein interaction network to pinpoint a specific set of NEPC maker genes namely CDHu40. These genes and scores based on their gene expression levels effectively distinguish NEPC samples and underscore the clinical prognostic significance and potential mechanism.

An Efficient Binary Sand Cat Swarm Optimization for Feature Selection in High-Dimensional Biomedical Data.

Recent breakthroughs are making a significant contribution to big data in biomedicine which are anticipated to assist in disease diagnosis and patient care management. To obtain relevant information from this data, effective administration and analysis are required. One of the major challenges associated with biomedical data analysis is the so-called "curse of dimensionality". For this issue, a new version of Binary Sand Cat Swarm Optimization (called PILC-BSCSO), incorporating a pinhole-imaging-based learning strategy and crossover operator, is presented for selecting the most informative features. First, the crossover operator is used to strengthen the search capability of BSCSO. Second, the pinhole-imaging learning strategy is utilized to effectively increase exploration capacity while avoiding premature convergence. The Support Vector Machine (SVM) classifier with a linear kernel is used to assess classification accuracy. The experimental results show that the PILC-BSCSO algorithm beats 11 cutting-edge techniques in terms of classification accuracy and the number of selected features using three public medical datasets. Moreover, PILC-BSCSO achieves a classification accuracy of 100% for colon cancer, which is difficult to classify accurately, based on just 10 genes. A real Liver Hepatocellular Carcinoma (TCGA-HCC) data set was also used to further evaluate the effectiveness of the PILC-BSCSO approach. PILC-BSCSO identifies a subset of five marker genes, including prognostic biomarkers HMMR, CHST4, and COL15A1, that have excellent predictive potential for liver cancer using TCGA data.

Hybrid Hypercube Optimization Search Algorithm and Multilayer Perceptron Neural Network for Medical Data Classification.

The hypercube optimization search (HOS) approach is a new efficient and robust metaheuristic algorithm that simulates the dove's movement in quest of new food sites in nature, utilizing hypercubes to depict the search zones. In medical informatics, the classification of medical data is one of the most challenging tasks because of the uncertainty and nature of healthcare data. This paper proposes the use of the HOS algorithm for training multilayer perceptrons (MLP), one of the most extensively used neural networks (NNs), to enhance its efficacy as a decision support tool for medical data classification. The proposed HOS-MLP model is tested on four significant medical datasets: orthopedic patients, diabetes, coronary heart disease, and breast cancer, to assess HOS's success in training MLP. For verification, the results are compared with eleven different classifiers and eight well-regarded MLP trainer metaheuristic algorithms: particle swarm optimization (PSO), biogeography-based optimizer (BBO), the firefly algorithm (FFA), artificial bee colony (ABC), genetic algorithm (GA), bat algorithm (BAT), monarch butterfly optimizer (MBO), and the flower pollination algorithm (FPA). The experimental results demonstrate that the MLP trained by HOS outperforms the other comparative models regarding mean square error (MSE), classification accuracy, and convergence rate. The findings also reveal that the HOS help the MLP to produce more accurate results than other classification algorithms for the prediction of diseases.

Gene selection using hybrid dragonfly black hole algorithm: A case study on RNA-seq COVID-19 data.

This paper introduces a new hybrid approach (DBH) for solving gene selection problem that incorporates the strengths of two existing metaheuristics: binary dragonfly algorithm (BDF) and binary black hole algorithm (BBHA). This hybridization aims to identify a limited and stable set of discriminative genes without sacrificing classification accuracy, whereas most current methods have encountered challenges in extracting disease-related information from a vast amount of redundant genes. The proposed approach first applies the minimum redundancy maximum relevancy (MRMR) filter method to reduce the dimensionality of feature space and then utilizes the suggested hybrid DBH algorithm to determine a smaller set of significant genes. The proposed approach was evaluated on eight benchmark gene expression datasets, and then, was compared against the latest state-of-art techniques to demonstrate algorithm efficiency. The comparative study shows that the proposed approach achieves a significant improvement as compared with existing methods in terms of classification accuracy and the number of selected genes. Moreover, the performance of the suggested method was examined on real RNA-Seq coronavirus-related gene expression data of asthmatic patients for selecting the most significant genes in order to improve the discriminative accuracy of angiotensin-converting enzyme 2 (ACE2). ACE2, as a coronavirus receptor, is a biomarker that helps to classify infected patients from uninfected in order to identify subgroups at risk for COVID-19. The result denotes that the suggested MRMR-DBH approach represents a very promising framework for finding a new combination of most discriminative genes with high classification accuracy.

Training Feedforward Neural Network Using Enhanced Black Hole Algorithm: A Case Study on COVID-19 Related ACE2 Gene Expression Classification.

The aim of this paper is twofold. First, black hole algorithm (BHA) is proposed as a new training algorithm for feedforward neural networks (FNNs), since most traditional and metaheuristic algorithms for training FNNs suffer from the problem of slow coverage and getting stuck at local optima. BHA provides a reliable alternative to address these drawbacks. Second, complementary learning components and Levy flight random walk are introduced into BHA to result in a novel optimization algorithm (BHACRW) for the purpose of improving the FNNs' accuracy by finding optimal weights and biases. Four benchmark functions are first used to evaluate BHACRW's performance in numerical optimization problems. Later, the classification performance of the suggested models, using BHA and BHACRW for training FNN, is evaluated against seven various benchmark datasets: iris, wine, blood, liver disorders, seeds, Statlog (Heart), balance scale. Experimental result demonstrates that the BHACRW performs better in terms of mean square error (MSE) and accuracy of training FNN, compared to standard BHA and eight well-known metaheuristic algorithms: whale optimization algorithm (WOA), biogeography-based optimizer (BBO), gravitational search algorithm (GSA), genetic algorithm (GA), cuckoo search (CS), multiverse optimizer (MVO), symbiotic organisms search (SOS), and particle swarm optimization (PSO). Moreover, we examined the classification performance of the suggested approach on the angiotensin-converting enzyme 2 (ACE2) gene expression as a coronavirus receptor, which has been overexpressed in human rhinovirus-infected nasal tissue. Results demonstrate that BHACRW-FNN achieves the highest accuracy on the dataset compared to other classifiers.

Gene selection using hybrid binary black hole algorithm and modified binary particle swarm optimization.

In cancer classification, gene selection is an important data preprocessing technique, but it is a difficult task due to the large search space. Accordingly, the objective of this study is to develop a hybrid meta-heuristic Binary Black Hole Algorithm (BBHA) and Binary Particle Swarm Optimization (BPSO) (4-2) model that emphasizes gene selection. In this model, the BBHA is embedded in the BPSO (4-2) algorithm to make the BPSO (4-2) more effective and to facilitate the exploration and exploitation of the BPSO (4-2) algorithm to further improve the performance. This model has been associated with Random Forest Recursive Feature Elimination (RF-RFE) pre-filtering technique. The classifiers which are evaluated in the proposed framework are Sparse Partial Least Squares Discriminant Analysis (SPLSDA); k-nearest neighbor and Naive Bayes. The performance of the proposed method was evaluated on two benchmark and three clinical microarrays. The experimental results and statistical analysis confirm the better performance of the BPSO (4-2)-BBHA compared with the BBHA, the BPSO (4-2) and several state-of-the-art methods in terms of avoiding local minima, convergence rate, accuracy and number of selected genes. The results also show that the BPSO (4-2)-BBHA model can successfully identify known biologically and statistically significant genes from the clinical datasets.

Meta-analysis of miRNA expression profiles for prostate cancer recurrence following radical prostatectomy.

BACKGROUND: Prostate cancer (PCa) is a leading reason of death in men and the most diagnosed malignancies in the western countries at the present time. After radical prostatectomy (RP), nearly 30% of men develop clinical recurrence with high serum prostate-specific antigen levels. An important challenge in PCa research is to identify effective predictors of tumor recurrence. The molecular alterations in microRNAs are associated with PCa initiation and progression. Several miRNA microarray studies have been conducted in recurrence PCa, but the results vary among different studies. METHODS: We conducted a meta-analysis of 6 available miRNA expression datasets to identify a panel of co-deregulated miRNA genes and overlapping biological processes. The meta-analysis was performed using the 'MetaDE' package, based on combined P-value approaches (adaptive weight and Fisher's methods), in R version 3.3.1. RESULTS: Meta-analysis of six miRNA datasets revealed miR-125A, miR-199A-3P, miR-28-5P, miR-301B, miR-324-5P, miR-361-5P, miR-363*, miR-449A, miR-484, miR-498, miR-579, miR-637, miR-720, miR-874 and miR-98 are commonly upregulated miRNA genes, while miR-1, miR-133A, miR-133B, miR-137, miR-221, miR-340, miR-370, miR-449B, miR-489, miR-492, miR-496, miR-541, miR-572, miR-583, miR-606, miR-624, miR-636, miR-639, miR-661, miR-760, miR-890, and miR-939 are commonly downregulated miRNA genes in recurrent PCa samples in comparison to non-recurrent PCa samples. The network-based analysis showed that some of these miRNAs have an established prognostic significance in other cancers and can be actively involved in tumor growth. Gene ontology enrichment revealed many target genes of co-deregulated miRNAs are involved in "regulation of epithelial cell proliferation" and "tissue morphogenesis". Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that these miRNAs regulate cancer pathways. The PPI hub proteins analysis identified CTNNB1 as the most highly ranked hub protein. Besides, common pathway analysis showed that TCF3, MAX, MYC, CYP26A1, and SREBF1 significantly interact with those DE miRNA genes. The identified genes have been known as tumor suppressors and biomarkers which are closely related to several cancer types, such as colorectal cancer, breast cancer, PCa, gastric, and hepatocellular carcinomas. Additionally, it was shown that the combination of DE miRNAs can assist in the more specific detection of the PCa and prediction of biochemical recurrence (BCR). CONCLUSION: We found that the identified miRNAs through meta-analysis are candidate predictive markers for recurrent PCa after radical prostatectomy.

A Meta-Analysis: Identification of Common Mir-145 Target Genes that have Similar Behavior in Different GEO Datasets.

BACKGROUND: MicroRNAs, which are small regulatory RNAs, post-transcriptionally regulate gene expression by binding 3'-UTR of their mRNA targets. Their deregulation has been shown to cause increased proliferation, migration, invasion, and apoptosis. miR-145, an important tumor supressor microRNA, has shown to be downregulated in many cancer types and has crucial roles in tumor initiation, progression, metastasis, invasion, recurrence, and chemo-radioresistance. Our aim is to investigate potential common target genes of miR-145, and to help understanding the underlying molecular pathways of tumor pathogenesis in association with those common target genes. METHODS: Eight published microarray datasets, where targets of mir-145 were investigated in cell lines upon mir-145 over expression, were included into this study for meta-analysis. Inter group variabilities were assessed by box-plot analysis. Microarray datasets were analyzed using GEOquery package in Bioconducter 3.2 with R version 3.2.2 and two-way Hierarchical Clustering was used for gene expression data analysis. RESULTS: Meta-analysis of different GEO datasets showed that UNG, FUCA2, DERA, GMFB, TF, and SNX2 were commonly downregulated genes, whereas MYL9 and TAGLN were found to be commonly upregulated upon mir-145 over expression in prostate, breast, esophageal, bladder cancer, and head and neck squamous cell carcinoma. Biological process, molecular function, and pathway analysis of these potential targets of mir-145 through functional enrichments in PPI network demonstrated that those genes are significantly involved in telomere maintenance, DNA binding and repair mechanisms. CONCLUSION: As a conclusion, our results indicated that mir-145, through targeting its common potential targets, may significantly contribute to tumor pathogenesis in distinct cancer types and might serve as an important target for cancer therapy.

Biomarker discovery based on BBHA and AdaboostM1 on microarray data for cancer classification.

In this paper, a new approach based on Binary Black Hole Algorithm (BBHA) and Adaptive Boosting version Ml (AdaboostM1) is proposed for finding genes that can classify the group of cancers correctly. In this approach, BBHA is used to perform gene selection and AdaboostM1 with 10-fold cross validation is adopted as the classifier. Also, to find the relation between the biomarkers for biological point of view, decision tree algorithm (C4.5) is utilized. The proposed approach is tested on three benchmark microarrays. The experimental results show that our proposed method can select the most informative gene subsets by reducing the dimension of the data set and improve classification accuracy as compared to several recent studies.

Improving medical diagnosis reliability using Boosted C5.0 decision tree empowered by Particle Swarm Optimization.

Improving accuracy of supervised classification algorithms in biomedical applications is one of active area of research. In this study, we improve the performance of Particle Swarm Optimization (PSO) combined with C4.5 decision tree (PSO+C4.5) classifier by applying Boosted C5.0 decision tree as the fitness function. To evaluate the effectiveness of our proposed method, it is implemented on 1 microarray dataset and 5 different medical data sets obtained from UCI machine learning databases. Moreover, the results of PSO + Boosted C5.0 implementation are compared to eight well-known benchmark classification methods (PSO+C4.5, support vector machine under the kernel of Radial Basis Function, Classification And Regression Tree (CART), C4.5 decision tree, C5.0 decision tree, Boosted C5.0 decision tree, Naive Bayes and Weighted K-Nearest neighbor). Repeated five-fold cross-validation method was used to justify the performance of classifiers. Experimental results show that our proposed method not only improve the performance of PSO+C4.5 but also obtains higher classification accuracy compared to the other classification methods.