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Understanding breast cancer drug response mechanisms can play a crucial role in improving treatment outcomes and survival rates. Existing bioinformatics-based approaches are far from perfect and do not adopt computational methods based on advanced artificial intelligence concepts. Therefore, we introduce a novel computational framework based on an efficient support vector machine (esvm) working as follows: First, we downloaded and processed three gene expression datasets related to breast cancer responding and non-responding to treatments from the gene expression omnibus (GEO) according to the following GEO accession numbers: GSE130787, GSE140494, and GSE196093. Our method esvm is formulated as a constrained optimization problem in its dual form as a function of λ. We recover the importance of each gene as a function of λ, y, and x. Then, we select p genes out of n, which are provided as input to enrichment analysis tools, Enrichr and Metascape. Compared to existing baseline methods, including deep learning, results demonstrate the superiority and efficiency of esvm, achieving high-performance results and having more expressed genes in well-established breast cancer cell lines, including MD-MB231, MCF7, and HS578T. Moreover, esvm is able to identify (1) various drugs, including clinically approved ones (e.g., tamoxifen and erlotinib); (2) seventy-four unique genes (including tumor suppression genes such as TP53 and BRCA1); and (3) thirty-six unique TFs (including SP1 and RELA). These results have been reported to be linked to breast cancer drug response mechanisms, progression, and metastasizing. Our method is available publicly on the maGENEgerZ web server.

Transmission electron microscopy imaging provides a unique opportunity to inspect the detailed structure of infected lung cells with SARS-CoV-2. Unlike previous studies, this novel study aims to investigate COVID-19 classification at the lung cellular level in response to SARS-CoV-2. Particularly, differentiating between healthy and infected human alveolar type II (hAT2) cells with SARS-CoV-2. Hence, we explore the feasibility of deep transfer learning (DTL) and introduce a highly accurate approach that works as follows: First, we downloaded and processed 286 images pertaining to healthy and infected hAT2 cells obtained from the electron microscopy public image archive. Second, we provided processed images to two DTL computations to induce ten DTL models. The first DTL computation employs five pre-trained models (including DenseNet201 and ResNet152V2) trained on more than one million images from the ImageNet database to extract features from hAT2 images. Then, it flattens and provides the output feature vectors to a trained, densely connected classifier with the Adam optimizer. The second DTL computation works in a similar manner, with a minor difference in that we freeze the first layers for feature extraction in pre-trained models while unfreezing and jointly training the next layers. The results using five-fold cross-validation demonstrated that TFeDenseNet201 is 12.37× faster and superior, yielding the highest average ACC of 0.993 (F1 of 0.992 and MCC of 0.986) with statistical significance (P<2.2×10−16 from a t-test) compared to an average ACC of 0.937 (F1 of 0.938 and MCC of 0.877) for the counterpart (TFtDenseNet201), showing no significance results (P=0.093 from a t-test).

MotivationTensor decomposition (TD)-based unsupervised feature extraction (FE) has proven effective for a wide range of bioinformatics applications ranging from biomarker identification to the identification of disease-causing genes and drug repositioning. However, TD-based unsupervised FE failed to gain widespread acceptance due to the lack of user-friendly tools for non-experts.ResultsWe developed two bioconductor packages—TDbasedUFE and TDbasedUFEadv—that enable researchers unfamiliar with TD to utilize TD-based unsupervised FE. The packages facilitate the identification of differentially expressed genes and multiomics analysis. TDbasedUFE was found to outperform two state-of-the-art methods, such as DESeq2 and DIABLO.Availability and implementationTDbasedUFE and TDbasedUFEadv are freely available as R/Bioconductor packages, which can be accessed at https://bioconductor.org/packages/TDbasedUFE and https://bioconductor.org/packages/TDbasedUFEadv, respectively.

Abstract The integrated analysis of multiple gene expression profiles previously measured in distinct studies is problematic since missing both sample matches and common labels prevent their integration in fully data-driven, unsupervised training. In this study, we propose a strategy to enable the integration of multiple gene expression profiles among multiple independent studies with neither labeling nor sample matching using tensor decomposition unsupervised feature extraction. We apply this strategy to Alzheimer’s disease (AD)-related gene expression profiles that lack precise correspondence among samples, including AD single-cell RNA sequence (scRNA-seq) data. We were able to select biologically reasonable genes using the integrated analysis. Overall, integrated gene expression profiles can function analogously to prior- and/or transfer-learning strategies in other machine-learning applications. For scRNA-seq, the proposed approach significantly reduces the required computational memory.

Abstract Tensor decomposition- and principal component analysis-based unsupervised feature extraction were proposed almost 5 and 10 years ago, respectively; although these methods have been successfully applied to a wide range of genome analyses, including drug repositioning, biomarker identification, and disease-causing genes’ identification, some fundamental problems have been identified: the number of genes identified was too small to assume that there were no false negatives, and the histogram of P values derived was not fully coincident with the null hypothesis that principal component and singular value vectors follow the Gaussian distribution. Optimizing the standard deviation such that the histogram of P values is as much as possible coincident with the null hypothesis results in an increase in the number and biological reliability of the selected genes. Our contribution was that we improved these methods so as to be able to select biologically more reasonable differentially expressed genes than the state of art methods that must empirically assume negative binomial distributions and dispersion relation, which is required for the selecting more expressed genes than less expressed ones, which can be achieved by the proposed methods that do not have to assume these.

Abstract Background Feature selection of multi-omics data analysis remains challenging owing to the size of omics datasets, comprising approximately $$10^2$$ 10 2 – $$10^5$$ 10 5 features. In particular, appropriate methods to weight individual omics datasets are unclear, and the approach adopted has substantial consequences for feature selection. In this study, we extended a recently proposed kernel tensor decomposition (KTD)-based unsupervised feature extraction (FE) method to integrate multi-omics datasets obtained from common samples in a weight-free manner. Method KTD-based unsupervised FE was reformatted as the collection of kernelized tensors sharing common samples, which was applied to synthetic and real datasets. Results The proposed advanced KTD-based unsupervised FE method showed comparative performance to that of the previously proposed KTD method, as well as tensor decomposition-based unsupervised FE, but required reduced memory and central processing unit time. Moreover, this advanced KTD method, specifically designed for multi-omics analysis, attributes P values to features, which is rare for existing multi-omics–oriented methods. Conclusions The sample R code is available at https://github.com/tagtag/MultiR/ .

Integration of gene expression (GE) and protein–protein interaction (PPI) is not straightforward because the former is provided as a matrix, whereas the latter is provided as a network. In many cases, genes processed with GE analysis are refined further based on a PPI network or vice versa. This is hardly regarded as a true integration of GE and PPI. To address this problem, we proposed a tensor decomposition (TD)-based method that can integrate GE and PPI prior to any analyses where PPI is also formatted as a matrix to which singular value decomposition (SVD) is applied. Integrated analyses with TD improved the coincidence between vectors attributed to samples and class labels over 27 cancer types retrieved from The Cancer Genome Atlas Program (TCGA) toward five class labels. Enrichment using genes selected with this strategy was also improved with the integration using TD. The PPI network associated with the information on the strength of the PPI can improve the performance than PPI that stores only if the interaction exists in individual pairs. In addition, even restricting genes to the intersection of GE and PPI can improve coincidence and enrichment.

Identifying differentially expressed genes is difficult because of the small number of available samples compared with the large number of genes. Conventional gene selection methods employing statistical tests have the critical problem of heavy dependence of P-values on sample size. Although the recently proposed principal component analysis (PCA) and tensor decomposition (TD)-based unsupervised feature extraction (FE) has often outperformed these statistical test-based methods, the reason why they worked so well is unclear. In this study, we aim to understand this reason in the context of projection pursuit (PP) that was proposed a long time ago to solve the problem of dimensions; we can relate the space spanned by singular value vectors with that spanned by the optimal cluster centroids obtained from K-means. Thus, the success of PCA- and TD-based unsupervised FE can be understood by this equivalence. In addition to this, empirical threshold adjusted P-values of 0.01 assuming the null hypothesis that singular value vectors attributed to genes obey the Gaussian distribution empirically corresponds to threshold-adjusted P-values of 0.1 when the null distribution is generated by gene order shuffling. For this purpose, we newly applied PP to the three data sets to which PCA and TD based unsupervised FE were previously applied; these data sets treated two topics, biomarker identification for kidney cancers (the first two) and the drug discovery for COVID-19 (the thrid one). Then we found the coincidence between PP and PCA or TD based unsupervised FE is pretty well. Shuffling procedures described above are also successfully applied to these three data sets. These findings thus rationalize the success of PCA- and TD-based unsupervised FE for the first time.

Firstly, I apologize for the delayed publication of this Special Issue in the form of a book title [...]

Abstract Background Although in silico drug discovery is necessary for drug development, two major strategies, a structure-based and ligand-based approach, have not been completely successful. Currently, the third approach, inference of drug candidates from gene expression profiles obtained from the cells treated with the compounds under study requires the use of a training dataset. Here, the purpose was to develop a new approach that does not require any pre-existing knowledge about the drug–protein interactions, but these interactions can be inferred by means of an integrated approach using gene expression profiles obtained from the cells treated with the analysed compounds and the existing data describing gene–gene interactions. Results In the present study, using tensor decomposition-based unsupervised feature extraction, which represents an extension of the recently proposed principal-component analysis-based feature extraction, gene sets and compounds with a significant dose-dependent activity were screened without any training datasets. Next, after these results were combined with the data showing perturbations in single-gene expression profiles, genes targeted by the analysed compounds were inferred. The set of target genes thus identified was shown to significantly overlap with known target genes of the compounds under study. Conclusions The method is specifically designed for large-scale datasets (including hundreds of treatments with compounds), not for conventional small-scale datasets. The obtained results indicate that two compounds that have not been extensively studied, WZ-3105 and CGP-60474, represent promising drug candidates targeting multiple cancers, including melanoma, adenocarcinoma, liver carcinoma, and breast, colon, and prostate cancers, which were analysed in this in silico study.

Background: COVID-19 is a critical pandemic that has affected human communities worldwide, and there is an urgent need to develop effective drugs. Although there are a large number of candidate drug compounds that may be useful for treating COVID-19, the evaluation of these drugs is time-consuming and costly. Thus, screening to identify potentially effective drugs prior to experimental validation is necessary. Method: In this study, we applied the recently proposed method tensor decomposition (TD)-based unsupervised feature extraction (FE) to gene expression profiles of multiple lung cancer cell lines infected with severe acute respiratory syndrome coronavirus 2. We identified drug candidate compounds that significantly altered the expression of the 163 genes selected by TD-based unsupervised FE. Results: Numerous drugs were successfully screened, including many known antiviral drug compounds such as C646, chelerythrine chloride, canertinib, BX-795, sorafenib, sorafenib, QL-X-138, radicicol, A-443654, CGP-60474, alvocidib, mitoxantrone, QL-XII-47, geldanamycin, fluticasone, atorvastatin, quercetin, motexafin gadolinium, trovafloxacin, doxycycline, meloxicam, gentamicin, and dibromochloromethane. The screen also identified ivermectin, which was first identified as an anti-parasite drug and recently the drug was included in clinical trials for SARS-CoV-2. Conclusions: The drugs screened using our strategy may be effective candidates for treating patients with COVID-19.

The development of the medical applications for substances or materials that contact cells is important. Hence, it is necessary to elucidate how substances that surround cells affect gene expression during incubation. In the current study, we compared the gene expression profiles of cell lines that were in contact with collagen–glycosaminoglycan mesh and control cells. Principal component analysis-based unsupervised feature extraction was applied to identify genes with altered expression during incubation in the treated cell lines but not in the controls. The identified genes were enriched in various biological terms. Our method also outperformed a conventional methodology, namely, gene selection based on linear regression with time course.

Although single-cell RNA sequencing (scRNA-seq) technology is newly invented and a promising one, but because of lack of enough information that labels individual cells, it is hard to interpret the obtained gene expression of each cell. Because of insufficient information available, unsupervised clustering, for example, t-distributed stochastic neighbor embedding and uniform manifold approximation and projection, is usually employed to obtain low-dimensional embedding that can help to understand cell–cell relationship. One possible drawback of this strategy is that the outcome is highly dependent upon genes selected for the usage of clustering. In order to fulfill this requirement, there are many methods that performed unsupervised gene selection. In this study, a tensor decomposition (TD)-based unsupervised feature extraction (FE) was applied to the integration of two scRNA-seq expression profiles that measure human and mouse midbrain development. TD-based unsupervised FE could select not only coincident genes between human and mouse but also biologically reliable genes. Coincidence between two species as well as biological reliability of selected genes is increased compared with that using principal component analysis (PCA)-based FE applied to the same data set in the previous study. Since PCA-based unsupervised FE outperformed the other three popular unsupervised gene selection methods, highly variable genes, bimodal genes, and dpFeature, TD-based unsupervised FE can do so as well. In addition to this, 10 transcription factors (TFs) that might regulate selected genes and might contribute to midbrain development were identified. These 10 TFs, BHLHE40, EGR1, GABPA, IRF3, PPARG, REST, RFX5, STAT3, TCF7L2, and ZBTB33, were previously reported to be related to brain functions and diseases. TD-based unsupervised FE is a promising method to integrate two scRNA-seq profiles effectively.

N6-methyladenosine (m6A) editing is the most common RNA modification known to contribute to various biological processes. Nevertheless, the mechanism by which m6A regulates transcription is unclear. Recently, it was proposed that m6A controls transcription through histone modification, although no comprehensive analysis using this dataset was performed. In this study, we applied tensor decomposition (TD)-based unsupervised feature extraction (FE) to a dataset composed of mouse embryonic stem cells (mESC) and a human cancer cell line (HEC-1-A) and successfully identified two sets of genes significantly overlapping between humans and mice (63 significantly overlapped genes among a total of 16,763 genes common to the two species). These significantly overlapped genes occupy at most 10% genes from both gene sets. Using these two sets of genes, we identified transcription factors (TFs) that m6A might recruit, biological processes that m6A might contribute to, and diseases that m6A might cause; they also largely overlap with each other. Since they were commonly identified using two independent datasets, the results regarding these TFs, biological processes, and diseases should be highly robust and trustworthy. It will help us to understand the mechanisms by which m6A contributes to biological processes.

Brain tumor classification is a challenging task in the field of medical image processing. Technology has now enabled medical doctors to have additional aid for diagnosis. We aim to classify brain tumors using MRI images, which were collected from anonymous patients and artificial brain simulators. In this article, we carry out a comparative study between Simple Artificial Neural Networks with dropout, Basic Convolutional Neural Networks (CNN), and Dilated Convolutional Neural Networks. The experimental results shed light on the high classification performance (accuracy 97%) of Dilated CNN. On the other hand, Dilated CNN suffers from the gridding phenomenon. An incremental, even number dilation rate takes advantage of the reduced computational overhead and also overcomes the adverse effects of gridding. Comparative analysis between different combinations of dilation rates for the different convolution layers, help validate the results. The computational overhead in terms of efficiency for training the model to reach an acceptable threshold accuracy of 90% is another parameter to compare the model performance.

Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disease characterized by both motor and nonmotor features. The diagnose of PD is based on a review of patients’ signs and symptoms, and neurological and physical examinations. So far, no tests have been devised that can conclusively diagnose PD. In this study, we explore both microRNA and gene biomarkers for PD. Microarray gene expression profiles for PD patients and healthy control are analyzed using a principal component analysis (PCA)-based unsupervised feature extraction (FE). 244 genes are selected to be potential gene biomarkers for PD. In addition, we implement these genes into Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and find that the 15 microRNAs (miRNAs), hsa-miR-92a-3p, 16-5p, 615-3p, 877-3p, 100-5p, 320a, 877-5p, 23a-3p, 484, 23b-3p, 15a-5p, 324-3p, 19b-3p, 7b-5p and 505-3p, significantly target these 244 genes. These miRNAs are shown to be significantly related to PD. This reveals that both selected genes and miRNAs are potential biomarkers for PD.

Background Epigenetics is an important mRNA expression regulator. However, how distinct epigenetic factors, such as microRNAs (miRNAs) and promoter methylation, cooperatively regulate mRNA expression is rarely discussed. Recently, apparent miRNA regulation of promoter methylation was identified by bioinformatic analysis; however, it has not yet been experimentally confirmed. If miRNA regulation of other epigenetic factors were identified, it would reveal another layer of epigenetic regulation. In this paper, histone modifications (H3K4me1, H3K4me3, H3K27me3, H3K27ac, H3K9ac, and H2AZ) during mammalian spermatogenesis were studied and the apparent miRNA-target-specific histone modification was investigated by bioinformatic analyses of publicly available datasets. Results We identified several miRNAs’ target genes that are significantly associated with histone modification during mammalian spermatogenesis. MiRNAs that target genes associated with the most significant histone modifications are expressed before or during spermatogenesis; thus the results were convincing. Conclusions In this paper, we identified apparent miRNA regulation of histone modifications using a bioinformatics approach. The biological mechanisms of this effect should be further experimentally investigated.