Differential expression of splicing machinery components in the liver of patients with and without steatosis with obesity. (A) Study design and pattern of dysregulation of spliceosome components and splicing factors in the liver of patients with and without steatosis with obesity. (Left) A graphical summary of the study design is shown. (Right) A schematic representation of fold-change levels of spliceosome components and splicing factors between the liver of patients with and without steatosis with obesity, represented in red (increase) or blue (decrease), is depicted. (B) Expression levels and receiver operating characteristic (ROC) curves of significantly altered spliceosome components and splicing factors in the liver of patients with obesity and steatosis compared with patients with obesity without steatosis. mRNA expression levels (adjusted by an NF, calculated from the expression level of HPRT and ACTB) of the different spliceosome components (first and second rows) and splicing factors (third and fourth rows) significantly altered in the liver of women with obesity with steatosis (ST) and without steatosis (NON ST). Values represent the means ± SEM. Asterisks indicate values that significantly differ from patients without steatosis (t test: *P < 0.05, **P < 0.01, ***P < 0.001). ROC curve analyses, to determine the accuracy of the components of the splicing machinery and splicing factors to discriminate between patients, with or without liver steatosis, are included below each graph. (C) ROC curves of subsets of spliceosome components and splicing factors generated by Random Forest computational algorithm, followed by crossvalidation analysis, considering the expression of a selection of the most relevant and discriminatory splicing machinery components. Specifically, three subset of specific splicing machinery components are included: PTBP1, RBM45, SRRM1, RNU4, and RNU6ATAC; PTBP1, RBM22, SRSF1, SRRM1, SNRNP70, and RNU6ATAC; and CELF1, PTBP1, RBM22, RBM3, SRRM1, and RNU6. AUC, area under curve.
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