scholarly journals Tensor decomposition-Based Unsupervised Feature Extraction Applied to Single-Cell Gene Expression Analysis

2019 ◽  
Author(s):  
Y-h. Taguchi ◽  
Turki Turki

ABSTRACTAlthough single cell RNA sequencing (scRNA-seq) technology is newly invented and promising one, because of lack of enough information that labels individual cells, it is hard to interpret the obtained gene expression of each cell. Because of this insufficient information available, unsupervised clustering, e.g., 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 not only select 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 principal component analysis (PCA) based FE applied to the same data set in the previous study. Since PCA based unsupervised FE outperformed 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, ten transcription factors (TFs) that might regulate selected genes and might contribute to midbrain development are identified. These ten 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.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kota Fujisawa ◽  
Mamoru Shimo ◽  
Y.-H. Taguchi ◽  
Shinya Ikematsu ◽  
Ryota Miyata

AbstractCoronavirus disease 2019 (COVID-19) is raging worldwide. This potentially fatal infectious disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the complete mechanism of COVID-19 is not well understood. Therefore, we analyzed gene expression profiles of COVID-19 patients to identify disease-related genes through an innovative machine learning method that enables a data-driven strategy for gene selection from a data set with a small number of samples and many candidates. Principal-component-analysis-based unsupervised feature extraction (PCAUFE) was applied to the RNA expression profiles of 16 COVID-19 patients and 18 healthy control subjects. The results identified 123 genes as critical for COVID-19 progression from 60,683 candidate probes, including immune-related genes. The 123 genes were enriched in binding sites for transcription factors NFKB1 and RELA, which are involved in various biological phenomena such as immune response and cell survival: the primary mediator of canonical nuclear factor-kappa B (NF-κB) activity is the heterodimer RelA-p50. The genes were also enriched in histone modification H3K36me3, and they largely overlapped the target genes of NFKB1 and RELA. We found that the overlapping genes were downregulated in COVID-19 patients. These results suggest that canonical NF-κB activity was suppressed by H3K36me3 in COVID-19 patient blood.


2017 ◽  
Author(s):  
Y-h. Taguchi

AbstractIdentifying drug target genes in gene expression profiles is not straightforward. Because a drug targets not mRNAs but proteins, mRNA expression of drug target genes is not always altered. In addition, the interaction between a drug and protein can be context dependent; this means that simple drug incubation experiments on cell lines do not always reflect the real situation during active disease. In this paper, I apply tensor decomposition-based unsupervised feature extraction to the integrated analysis of gene expression between heart failure and the DrugMatrix dataset where comprehensive data on gene expression during various drug treatments of rats were reported. I found that this strategy, in a fully unsupervised manner, enables us to identify a combined set of genes and compounds, for which various associations with heart failure were reported.


2021 ◽  
Author(s):  
Y-h. Taguchi ◽  
Turki Turki

Analysis of single-cell multiomics datasets is a novel topic and is considerably challenging because such datasets contain a large number of features with numerous missing values. In this study, we implemented a recently proposed tensor-decomposition (TD)--based unsupervised feature extraction (FE) technique to address this difficult problem. The technique can successfully integrate single-cell multiomics data composed of gene expression, DNA methylation, and accessibility. Although the last two have large dimensions, as many as ten million, containing only a few percentages of non-zero values, TD-based unsupervised FE can integrate three omics datasets without filling missing values. Together with UMAP, which is used frequently when embedding single-cell measurements into two-dimensional space, TD-based unsupervised FE can produce two-dimensional embedding coincident with classification when integrating single-cell omics datasets. Genes selected based on TD-based unsupervised FE were also significantly related to reasonable biological roles.


Author(s):  
Y-h. Taguchi ◽  
Turki Turki

ABSTRACTGene expression profiles of tissues treated with drugs have recently been used to infer clinical outcomes. Although this method is often successful from the application point of view, gene expression altered by drugs is rarely analyzed in detail, because of the extremely large number of genes involved. Here, we applied tensor decomposition (TD)-based unsupervised feature extraction (FE) to the gene expression profiles of 24 mouse tissues treated with 15 drugs. TD-based unsupervised FE enabled identification of the common effects of 15 drugs including an interesting universal feature: these drugs affect genes in a gene-group-wide manner and were dependent on three tissue types (neuronal, muscular, and gastroenterological). For each tissue group, TD-based unsupervised FE enabled identification of a few tens to a few hundreds of genes affected by the drug treatment. These genes are distinctly expressed between drug treatments and controls as well as between tissues in individual tissue groups and other tissues. We also validated the assignment of genes to individual tissue groups using multiple enrichment analyses. We conclude that TD-based unsupervised FE is a promising method for integrated analysis of gene expression profiles from multiple tissues treated with multiple drugs in a completely unsupervised manner.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sanjiban Sekhar Roy ◽  
Y.-H. Taguchi

AbstractAlthough hypoxia is a critical factor that can drive the progression of various diseases, the mechanism underlying hypoxia itself remains unclear. Recently, m6A has been proposed as an important factor driving hypoxia. Despite successful analyses, potential genes were not selected with statistical significance but were selected based solely on fold changes. Because the number of genes is large while the number of samples is small, it was impossible to select genes using conventional feature selection methods with statistical significance. In this study, we applied the recently proposed principal component analysis (PCA), tensor decomposition (TD), and kernel tensor decomposition (KTD)-based unsupervised feature extraction (FE) to a hypoxia data set. We found that PCA, TD, and KTD-based unsupervised FE could successfully identify a limited number of genes associated with altered gene expression and m6A profiles, as well as the enrichment of hypoxia-related biological terms, with improved statistical significance.


Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1442
Author(s):  
Y-H. Taguchi ◽  
Turki Turki

Analysis of single-cell multiomics datasets is a novel topic and is considerably challenging because such datasets contain a large number of features with numerous missing values. In this study, we implemented a recently proposed tensor-decomposition (TD)-based unsupervised feature extraction (FE) technique to address this difficult problem. The technique can successfully integrate single-cell multiomics data composed of gene expression, DNA methylation, and accessibility. Although the last two have large dimensions, as many as ten million, containing only a few percentage of nonzero values, TD-based unsupervised FE can integrate three omics datasets without filling in missing values. Together with UMAP, which is used frequently when embedding single-cell measurements into two-dimensional space, TD-based unsupervised FE can produce two-dimensional embedding coincident with classification when integrating single-cell omics datasets. Genes selected based on TD-based unsupervised FE are also significantly related to reasonable biological roles.


Polymers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 4117
Author(s):  
Y-h. Taguchi ◽  
Turki Turki

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.


2021 ◽  
Author(s):  
Y-h. Taguchi ◽  
Turki Turki

AbstractDevelopment of the medical applications for substances or materials that contact the cells is important. Hence, it is necessary to elucidate how substance that surround cells affect the gene expression during incubation. Here, we compared the gene expression profiles of cell lines that were in contact with the 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.


Sign in / Sign up

Export Citation Format

Share Document