Phenomics (Cham, Switzerland)最新文献

Retinol, a pivotal regulator of cellular growth and apoptosis, has garnered substantial attention for its intricate involvement in cancer development. To explore Vitamin A's impact on lung adenocarcinoma (LUAD), we utilized comprehensive datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to dissect the intricate role of retinol in cancer progression. The unsupervised clustering analysis, grounded on retinol metabolism gene sets, divided patients into two distinct clusters, with cluster 1 exhibiting significantly inferior survival outcomes. Through differential analysis, we uncovered 349 differentially mutated and 394 differentially expressed genes between these clusters. Leveraging these discoveries, we built a seven-gene signature model that precisely predicted poorer survival for patients with a higher risk score, which was subsequently validated in four independent GEO cohorts, demonstrating its robustness and reliability. Our drug sensitivity analysis further revealed that high-risk patients were more susceptible to gefitinib and erlotinib. Notably, leveraging gene dependency scores and RNA-seq data from LUAD cell lines, we identified Phosphoribosylaminoimidazole Carboxylase And Phosphoribosylaminoimidazolesuccinocarboxamide Synthase (PAICS) as a potential therapeutic target. Single-RNA sequencing confirmed PAICS's predominant expression in cancer cells, and functional assays underscored its oncogenic role in promoting cell proliferation, migration, and invasion. These novel findings offer profound insights into potential therapeutic avenues for LUAD patients with poor prognoses, paving the way for future research endeavors.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-025-00223-y.

Primary dysmenorrhea (PDM) is a common cyclic menstrual pain that significantly affects the quality of life for women. Several epidemiological studies have suggested a potential association between PDM and mental health traits, including stress, depression, and anxiety. However, there is a lack of systematic investigation into whether a causal relationship exists between PDM and mental health phenotypes compared to other physical phenotypes. In this study, we conducted a large-scale phenome study on a cohort of 7401 young female Chinese college students to explore the association between PDM and various physical and mental health phenotypes. Using a multi-phenotype correlation network model, we discovered that the correlation between the PDM phenotypes and mental health phenotypes was the most dominant among the complex inter-connections across different categories of phenotypes. Furthermore, employing a two-sample Mendelian randomization analysis, we systematically elucidated the genomic-level impact of PDM on the mental health traits of young women. Specifically, we identified an increased risk of depression and anxiety associated with PDM, potentially influenced by several Single-nucleotide polymorphism (SNP) variants such as ZMIZ1, DIO1, GRIK4 and RBFOX1. This study offers valuable insights into the genetic mechanism through which dysmenorrhea impacts mental health, which contributes to a better understanding of the comprehensive management of PDM and its associated psychological challenges.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-024-00213-6.

Rapid and reliable nucleic acid detection methods are essential in clinical diagnostics and biotechnology. The clustered regularly interspaced short palindromic repeats (CRISPR) system is emerging as a next-generation nucleic acid detection technology, offering versatility, convenience and rapid detection. However, CRISPR methods are significantly limited by the protospacer adjacent motif (PAM) sequence, and achieving a one-pot reaction for detecting single nucleotide variations (SNVs) within a short time still remains challenging. Here, we developed a comprehensive method for screening PAM sequences, which significantly expands the CRISPR detection scope. Additionally, we also proposed a one-pot CRISPR method, termed "SIMPLE", capable of identifying SNVs within 30 min. We applied the SIMPLE method to the clinical diagnostics of drug-resistant bacteria and the screening of cancer hotspot mutations. The SIMPLE method successfully detected drug-resistant bacteria mediated by canonical PAM TTN sequence with a sensitivity of 10 copies per reaction and achieved 100% consistency with next-generation sequencing results. Furthermore, the SIMPLE method proved effective in detecting hotspot mutations in cancer, even at a low mutation rate of 1% in the presence of high background interference mediated by non-canonical PAM ATN sequence. Therefore, the SIMPLE method not only expands the CRISPR detection scope but also offers a one-pot reaction with high specificity for SNVs identification, making it a promising tool for next-generation molecular diagnostics.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-025-00240-x.

The impact of lipid metabolism on the development and prognosis of bone metastasis from breast cancer (BRCA) is currently unknown. Sequencing data of BRCA samples in this study were obtained from the University of California, Santa Cruz (UCSC) Xena database. The differentially expressed genes (DEGs1) between the BRCA group and the control group, the differentially expressed genes (DEGs2) between the bone metastasis group and the non-bone metastasis group, and the lipid metabolism score-related genes (LMSRGs) were intersected to obtain LMSRGs (DE-LMSRGs). Biomarkers were obtained using univariate logistic regression analysis, support vector machine recursive feature elimination (SVM-RFE) and multivariate logistic regression analysis for Correlation Analysis, Gene Set Enrichment Analysis, Immunohistochemistry, Co-creation of Networks, and Drug Prediction, and then analyses were performed using Immunohistochemistry, Western blot analyses to validate the samples. We identified two biomarkers (Regulator of G-protein Signaling 9 Binding Protein (RGS9BP) and suppressor of cytokine signaling 3 (SOCS3)). There were nine immune cells that were markedly differential between bone metastasis and non-bone metastasis groups, such as activated dendritic cell, neutrophil, plasmacytoid dendritic cell, etc. Then, the lncRNA-miRNA-mRNA network was created, including the regulated relationship pairs HLX-AS1-hsa-mir-541-SOCS3, ZNF337-AS1-hsa-mir-541-SOCS3. Molecular docking analyses have demonstrated that the complexes formed by SOCS3 alongside folic acid, estradiol, and S-Adenosylmethionine exhibit heightened stability. Similarly, the pairing of RGS9BP with benzopyrene showcases a notable degree of stability. Finally, the biomarkers were associated with angiogenesis scores and most angiogenesis related genes (ARGs). Our study identified two potential biomarkers (RGS9BP and SOCS3) for prognostic evaluation of bone metastasis patients with BRCA. These findings provided a scientific reference for further research on bone metastasis in BRCA patients.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-025-00221-0.

Alternative polyadenylation (APA) of mRNA is a widespread transcriptomic mechanism which fine-tunes gene expression and plays important roles in diverse biological processes. Of the different APA types, intronic polyadenylation is a prevalent but not well understood one. Although the upstream regulation of intronic polyadenylation is extensively investigated, the understanding of its biological function largely lags behind. Here, we discovered that intronic polyadenylation of glutaminase-encoding gene Glutaminase (GLS) generated an isoform termed Glutaminase C (GAC, encoding glutaminase C), which played regulatory roles in cellular senescence, the basis of individual aging and also an important anti-cancer mechanism. Reduced usage of GLS intronic polyadenylation (pA) site was consistent in both human and mouse senescence models. GAC protein mainly located in mitochondria, and downregulation of GAC induced cellular senescence in both human and mouse cells. Increased reactive oxygen species (ROS) level and decreased ATP synthesis explained the senescence-associated phenotypes in GAC deficient cells. Polyadenylation factor CPSF6 bound to the last exon of GAC to regulate its expression. Rescue experiment confirmed that CPSF6-GAC signal axis did play important roles in regulating cellular senescence. Together, the present study demonstrated for the first time that intronic polyadenylation could regulate cellular senescence, largely extending our understanding of the biological roles of intronic polyadenylation.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-024-00198-2.