We undertook a comprehensive proteogenomic characterization of 95 prospectively collected endometrial carcinomas, comprising 83 endometrioid and 12 serous tumors. This analysis revealed possible new consequences of perturbations to the p53 and Wnt/β-catenin pathways, identified a potential role for circRNAs in the epithelial-mesenchymal transition, and provided new information about proteomic markers of clinical and genomic tumor subgroups, including relationships to known druggable pathways. An extensive genome-wide acetylation survey yielded insights into regulatory mechanisms linking Wnt signaling and histone acetylation. We also characterized aspects of the tumor immune landscape, including immunogenic alterations, neoantigens, common cancer/testis antigens, and the immune microenvironment, all of which can inform immunotherapy decisions. Collectively, our multi-omic analyses provide a valuable resource for researchers and clinicians, identify new molecular associations of potential mechanistic significance in the development of endometrial cancers, and suggest novel approaches for identifying potential therapeutic targets.
Software component is an ideal means to improve reuse.But now component has not reached the practical level in the area of enterprise information due to the lack of combination of theory and engineering practice.This paper presents the concept of macro component in the field of enterprise information,discusses the implementation of component architecture platform and finally verifies its feasibility through practice.
Abstract Introduction Prostate cancer (PCa) is the second most frequent malignancy in men. Genetically engineered PCa mouse models (GEMMs) do not faithfully recapitulate human PCa progression. Reasons include architectural differences between the multi-lobulated mouse prostate and the human organ, choice of gene promoter (such as probasin, Pbsn) used to regulate transgene expression in GEMMs and lobular differences in susceptibility to castration. Imaging studies showed that androgen deprivation (first line therapy for metastatic PCa) by castration leads to dramatic regression of ventral prostate (VP) by up to 70%. Hence delineating cell type equivalents between the human and mouse prostates and mapping their distribution across the distinct lobes will provide fundamental knowledge to improve GEMMs, to effectively model human PCa. Methods We performed single-cell RNA sequencing (scRNA-seq) of C57BL6 and FVB mice prostates (n=10) to delineate cell type composition. We also conducted sc multi-omics (10X Multiome gene expression+ ATAC) and spatial transcriptomics (10X Visium) of prostates from mice that were unperturbed or castrated (C57BL6) to study transcriptional module (TM) alterations and spatial gene expression among the luminal epithelial (LE) cell types upon castration. Results Analyses of scRNA-seq data from 9,439 cells identified 22 different cell types from epithelial, stromal, and immune compartments and includes 9 different LE cell types that are under-studied. The lack of a standard nomenclature describing murine prostate LE cells in previous scRNA-seq studies poses a challenge for integrative analysis. We resolved this by integrating 4 independent scRNA-seq studies with our data to arrive at unified nomenclature and simultaneously validate our findings by statistical analysis. Multi-omics data analysis revealed LE cells TM differences, suggesting that LE cell diversity is developmentally triggered. Spatial transcriptomics and matched RNA in situ hybridization captured the lobe specific distribution patterns of LE cell types. For e.g., Pbsn+ LE cells were predominantly found across the AP, dorsal and lateral prostate, while Spink1+LE cells containing stemness associated genes (e.g.Tacstd2) were enriched in the VP. Analysis of the castration model revealed susceptibility differences to androgen deprivation among LE populations. Multi-omics analysis also showed a reduction in both chromatin accessibility and transcription of androgen regulated genes upon castration. Finally, cell type enrichment analysis suggests LE cells of the mouse AP and VP as equivalents of human LE and putative cell lineage signatures were enriched in PCa profiles, possibly stratifying PCa patient population. Conclusion A comprehensive mouse prostate cell atlas was built from two mouse strains. We provide a practical reference for the transcriptional and spatial profiles of each epithelial population. LE cells from AP and VP were most sensitive to castration and best represent human LE and the cell type specific genes identified here can guide future GEMM development. Citation Format: Hanbyul Cho, Yuping Zhang, Jean Tien, Jie Luo, June E. Wilke, Saravana M. Dhanasekaran, Rahul Mannan, Lisha Wang, Fengyun Su, Rui Wang, Evan T. Keller, Xuhong Cao, Sethu Pitchaya, Arul M. Chinnaiyan. Cellular cartography reveals transcriptional specificity and spatial organization of diverse luminal epithelial cells in the murine prostate [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A067.
Abstract With the advent of modern technologies, it is increasingly common to deal with data of large dimensions in various scientific fields of study. In this paper, we develop a Bayesian approach for the classification of multi‐subject high‐dimensional electroencephalography (EEG) data. In this EEG data, we have a matrix of covariates corresponding to each subject from either the alcoholic or control group. The matrix covariates have a natural spatial correlation based on the locations of the brain, and temporal correlation as the measurements are taken over time. We employ a divide and conquer strategy by building multiple local Bayesian models at each time point separately. We incorporate the spatial structure through the structured spike‐and‐slab prior, which has inherent variable selection properties. The temporal structure is incorporated within the prior by learning from the local model from the previous time point. We pool the information from the local models and use a weighted average to design a prediction method. We perform simulation studies to show the efficiency of our approach and demonstrate the local Bayesian modeling with a case study on EEG data.
We investigate maternal attitudes about gender equity and their relationship to educational expectations for sons and daughters in rural China using a survey of 2000 mothers and children in Gansu Province. Our findings suggest that most mothers hold egalitarian attitudes in terms of gender equity, but most expect future support from sons. Mothers’ own attitudes about gender equity, their expectations of future support, and their children’s past educational achievements predict their educational aspirations for their children. Interestingly, gender biases in aspirations appear more pronounced among mothers of mediocre students – mothers seem to be more forgiving of the mediocre academic performance of sons relative to daughters.
Let R be an n by n nontrivial real symmetric involution matrix, that is, R = R −1 = R T ≠ I n . An n × n complex matrix A is termed R ‐conjugate if , where denotes the conjugate of A . We give necessary and sufficient conditions for the existence of the Hermitian R ‐conjugate solution to the system of complex matrix equations A X = C and X B = D and present an expression of the Hermitian R ‐conjugate solution to this system when the solvability conditions are satisfied. In addition, the solution to an optimal approximation problem is obtained. Furthermore, the least squares Hermitian R ‐conjugate solution with the least norm to this system mentioned above is considered. The representation of such solution is also derived. Finally, an algorithm and numerical examples are given.
We present a new statistical method using longitudinal gene expression to predict quantitative outcomes of patients. Through simulations and application on a dataset of burn patients, the proposed method outperforms prediction methods using gene expression from individual time points or simply combining them together.DOI: http://dx.doi.org/10.4038/sljastats.v5i4.7787
Let be a given Hermitian matrix satisfying P 2 P I .Using the eigenvalue decomposition of , we consider the least squares solutions to the matrix equation P MZN S with the constraint PZ ZP .
Wiki is a kind of web-system to support co-creating,which,as a convenient knowledge-managing tool,has been popular in the Internet in recent years. As its application is expanding continually,it is supposed that Wiki will be developed gradually into a kind of E-learning in terms of study,training and education.Based on distance education and cooperative learning,this paper analyses the feasibility to apply Wiki to distance education from the aspects of its simpleness and convenience,openness and security,collaboration and communion.What's more,it puts forward in detail several ways to apply Wiki and finally,lists some notes the users should pay attention to.
In our previous study, the upregulation of adipophilin in lung adenocarcinoma were identified compared with normal lung tissues by quantitative proteomics. In this study, our aim was to verify the result from quantitative proteomics, further investigate the relationship between adipophilin expression and clinicopathologic factors of lung cancer patients. The expression levels of adipophilin were examined in 10 pairs of lung adenocarcinoma and normal lung tissues using western blotting and the expression and cellular distribution of adipophilin were determined by IHC in 62 formalin-fixed and paraffin embedded primary lung cancer specimens. Adipophilin expression was significantly higher in lung adenocarcinoma specimens than in normal tissues and lung squamous cell carcinomas (P<0.05). There were no significant difference of adipophilin expression between lung squamous cell carcinomas and normal lung tissues. The expression of adipophilin in lung cancer did not correlate with any clinicopathologic factors such as lymph node metastasis, patients' age, gender, tumor size, grade, and TNM stage. In Conclusion, Adipophilin was upregulated in lung adenocarcinoma, suggesting that adipophilin play an important role in tumorigenesis of lung adenocarcinoma and may serve as a potential marker for lung adenocarcinoma.
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