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. 2022 Sep 22;13(10):1698.
doi: 10.3390/genes13101698.

Estimation of Metabolic Effects upon Cadmium Exposure during Pregnancy Using Tensor Decomposition

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Estimation of Metabolic Effects upon Cadmium Exposure during Pregnancy Using Tensor Decomposition

Yuki Amakura et al. Genes (Basel). .

Abstract

A simple tensor decomposition model was applied to the liver transcriptome analysis data to elucidate the cause of cadmium-induced gene overexpression. In addition, we estimated the mechanism by which prenatal Cd exposure disrupts insulin metabolism in offspring. Numerous studies have reported on the toxicity of Cd. A liver transcriptome analysis revealed that Cd toxicity induces intracellular oxidative stress and mitochondrial dysfunction via changes in gene expression, which in turn induces endoplasmic reticulum-associated degradation via abnormal protein folding. However, the specific mechanisms underlying these effects remain unknown. In this study, we found that Cd-induced endoplasmic reticulum stress may promote increased expression of tumor necrosis factor-α (TNF-α). Based on the high expression of genes involved in the production of sphingolipids, it was also found that the accumulation of ceramide may induce intracellular oxidative stress through the overproduction of reactive oxygen species. In addition, the high expression of a set of genes involved in the electron transfer system may contribute to oxidative stress. These findings allowed us to identify the mechanisms by which intracellular oxidative stress leads to the phosphorylation of insulin receptor substrate 1, which plays a significant role in the insulin signaling pathway.

Keywords: cadmium exposure; insulin metabolism disruption; tensor decomposition.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The following figure depicts the four order tensors used in the analysis. The first dimension describes the genes, biological replicates are provided in the second dimension, time course is expressed as postnatal day (PND) in the third dimension, and presence or absence of Cd exposure is indicated in the fourth dimension (non-control refers to offspring born from Cd-exposed mothers, while control refers to offspring born from Cd-unexposed mothers.). Let N, M, K, and L denote the ranks of each dimension, (N, M, K, L) = (12,795, 3, 3, 2).
Figure 2
Figure 2
The entire flow of this analysis is represented in the flowchart diagram.
Figure 3
Figure 3
This bar chart represents the values of the singular value matrix Ul2j on the column vector. (First column: (a), second column: (b), and third column: (c)). For the analysis, there should be no variation in gene expression between individuals under identical conditions. Therefore, we chose l2 = 1.
Figure 4
Figure 4
This bar chart represents the values of the singular value matrix Ul3k on the column vector. (First column: (a), second column: (b), and third column: (c)). The objective is to isolate genes whose expression varies time-dependently due to Cd exposure. Therefore, we selected l3 = 2, which shows a monotonic decrease relative to PND.
Figure 5
Figure 5
This bar chart represents the values of the singular value matrix Ul4l on the column vector. (First column: (a), second column: (b)). The objective is to isolate genes that show differences in gene expression levels due to Cd exposure. Therefore, we selected l4 = 2, which has distinct positive and negative values.
Figure 6
Figure 6
The values of the vectors with (l2 = 1, l3 = 2, and l4 = 2) on the core tensor, from the first element to the eighteenth element, are represented using a bar chart. The top three with the highest values (l1 = 3, 11, 14) were selected. Owing to the rank of the tensor before decomposition, the nineteenth and subsequent elements are omitted because their values are very small.

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Grants and funding

This work was supported by Japan Society for the Promotion of Science, KAKENHI [grant numbers 19H05270, 20K12067, 20H04848] to Y.T.

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