Buttmackenzie6203
Coexistence of the two
variants R229Q and R291W in compound heterozygosis was a determinant of the FSGS phenotype. The presence of these variants alone in heterozygosis did not cause significant proteinuria.
Coexistence of the two NPHS2 variants R229Q and R291W in compound heterozygosis was a determinant of the FSGS phenotype. The presence of these variants alone in heterozygosis did not cause significant proteinuria.
Alternative splicing (AS) is reported to be related to the biological process of multiple malignancies. This study is conducted to identify survival-associated AS events and prognostic signatures that may serve as prognostic indicators for pancreatic cancer (PC).
Univariate Cox analysis was used to determine the survival-associated AS events in PC. Prognostic signatures were constructed by LASSO Cox analysis based on seven types of survival-associated AS events. The correlation between the expression of splicing factors (SFs) and the percent spliced in values of AS events was analyzed by Pearson correlation analysis. Risk scores were calculated to determine high- or low-risk patients with different types of AS events. Gene functional annotation analysis was performed to reveal pathways in which prognostic AS is enriched.
A total of 45,313 AS events in 10,624 genes were observed, and there were 1,565 AS events in 1,223 genes significantly correlated with overall survival for PC. Kaplan-Meier analysis, receiver-operator characteristic curve, univariate and multivariate Cox analyses showed that AS prognostic signatures could effectively predict prognosis of patients with PC. Splicing factors-AS regulatory networks were established to demonstrate the interaction between AS events and SFs.
The survival-associated AS events and prognostic signatures identified in this study can serve as useful tool for predicting prognosis of patients with PC. Moreover, the SF-AS regulatory networks may provide clues for the mechanisms underlying AS in PC.
The survival-associated AS events and prognostic signatures identified in this study can serve as useful tool for predicting prognosis of patients with PC. Moreover, the SF-AS regulatory networks may provide clues for the mechanisms underlying AS in PC.
Cholangiocarcinoma (CCA) is a rare disease, but it is amongst the most lethal cancers with a median survival under 1 year. Variations in DNA methylation and gene expression have been extensively studied in other cancers for their role in pathogenesis and disease prognosis, but these studies are very limited in CCA. This study focusses on the identification of DNA methylation and gene expression prognostic biomarkers using multi-omics data of CCA tumors from The Cancer Genome Atlas (TCGA).
We have conducted a genome-wide analysis of differential DNA methylation and gene/miRNA expression using data from 36 CCA tumor and 9 normal samples from TCGA. The impact of DNA methylation in promoters and long-range distal enhancers on the regulation and expression of CCA-associated genes was examined using linear regression. Next, we conducted network analyses on genes which are regulated by DNA methylation as well as by miRNA. Finally, we performed Kaplan-Meier and Cox proportional hazards regression analyses in ordee differentially expressed in CCA.
Based on the survival analysis, we conclude that DEPDC1, FUT4, MDK, PACS1, PIWIL4 genes, miR-22, miR-551b microRNAs, and cg27362525 and cg26597242 CpGs can strongly support their use as prognostic markers of CCA.
Based on the survival analysis, we conclude that DEPDC1, FUT4, MDK, PACS1, PIWIL4 genes, miR-22, miR-551b microRNAs, and cg27362525 and cg26597242 CpGs can strongly support their use as prognostic markers of CCA.The retrotransposon long interspersed nuclear element-1 (LINE-1) can autonomously increase its copy number within a host genome through the retrotransposition process. LINE-1 is active in the germline and in neural progenitor cells, and its somatic retrotransposition activity has a broad impact on neural development and susceptibility to neuropsychiatric disorders. The method to quantify the genomic copy number of LINE-1 would be important in unraveling the role of retrotransposition, especially in the brain. However, because of the species-specific evolution of LINE-1 sequences, methods for quantifying the copy number should be independently developed. Here, we developed a quantitative PCR (qPCR) assay to measure the copy number of active LINE-1 subfamilies in mice. Using the assay, we investigated aging-associated alterations of LINE-1 copy number in several brain regions in wild-type mice and Polg+/D257A mice as a model for accelerated aging. We found that aged Polg+/D257A mice showed higher levels of the type GfII LINE-1 in the basal ganglia than the wild-type mice did, highlighting the importance of assays that focus on an individual active LINE-1 subfamily.tRNA fragments (tRFs) are a class of small non-coding RNAs (sncRNAs) derived from tRNAs. tRFs are highly abundant in many cell types including stem cells and cancer cells, and are found in all domains of life. Epacadostat price Beyond translation control, tRFs have several functions ranging from transposon silencing to cell proliferation control. However, the analysis of tRFs presents specific challenges and their biogenesis is not well understood. They are very heterogeneous and highly modified by numerous post-transcriptional modifications. Here we describe a bioinformatic pipeline (tRFs-Galaxy) to study tRFs populations and shed light onto tRNA fragments biogenesis in Drosophila melanogaster. Indeed, we used small RNAs Illumina sequencing datasets extracted from wild type and mutant ovaries affecting two different highly conserved steps of tRNA biogenesis 5'pre-tRNA processing (RNase-P subunit Rpp30) and tRNA 2'-O-methylation (dTrm7_34 and dTrm7_32). Using our pipeline, we show how defects in tRNA biogenesis affect nuclear and mitochondrial tRFs populations and other small non-coding RNAs biogenesis, such as small nucleolar RNAs (snoRNAs). This tRF analysis workflow will advance the current understanding of tRFs biogenesis, which is crucial to better comprehend tRFs roles and their implication in human pathology.
