Significance Alternative splicing (AS) is an important mechanism of eukaryotic gene regulation. Deep RNA sequencing (RNA-Seq) has become a powerful approach for quantitative profiling AS. With the increasing capacity high-throughput sequencers, it common RNA-Seq studies AS to examine multiple biological replicates. We developed rMATS, new statistical method robust and flexible detection differential from replicate data. Besides analysis unpaired replicates, rMATS includes model specifically...

Ultra-deep RNA sequencing has become a powerful approach for genome-wide analysis of pre-mRNA alternative splicing. We develop MATS (multivariate transcript splicing), Bayesian statistical framework flexible hypothesis testing differential splicing patterns on RNA-Seq data. uses multivariate uniform prior to model the between-sample correlation in exon patterns, and Markov chain Monte Carlo (MCMC) method coupled with simulation-based adaptive sampling procedure calculate P -value false...

Huntington's disease (HD) is a fatal neurodegenerative caused by mutant huntingtin (htt) protein, and there are currently no effective treatments. Recently, we others demonstrated that silencing htt via RNA interference (RNAi) provides therapeutic benefit in HD mice. We have since found wild-type adult mouse striatum tolerated for at least 4 months. However, given the role of various cellular processes, it remains unknown whether nonallele-specific both viable strategy HD. Here, tested...

Cell-type and tissue-specific alternative splicing events are regulated by combinatorial control involving both abundant RNA binding proteins as well those with more discrete expression specialized functions. Epithelial Splicing Regulatory Proteins 1 2 (ESRP1 ESRP2) recently discovered epithelial-specific that promote of the epithelial variant FGFR2, ENAH, CD44, CTNND1 transcripts. To cataloge a larger set under regulation ESRPs we profiled changes induced interference-mediated knockdown...

Tissue-specific alternative splicing is achieved through the coordinated assembly of RNA binding proteins at specific sites to enhance or silence nearby splice sites. We used high-throughput sequencing (RNA-Seq) investigate complete spectrum events that are regulated by epithelium-specific regulatory ESRP1 and ESRP2. also combined this analysis with direct (DRS) reveal ESRP-mediated regulation polyadenylation. To define motifs mediate polyadenylation ESRP, SELEX-Seq was performed, coupling...

The Alu element has been a major source of new exons during primate evolution. Thousands human genes contain spliced derived from elements. However, identifying that have acquired genuine biological functions remains challenge. We investigated the creation and establishment in genes, using transcriptome profiles tissues generated by high-throughput RNA sequencing (RNA-Seq) combined with extensive RT-PCR analysis. More than 25% analyzed RNA-Seq estimated transcript inclusion levels at least...

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG expansion in the gene-encoding Huntingtin (HTT). Transcriptome dysregulation major feature of HD pathogenesis, as revealed large body work on gene expression profiling tissues from human patients and mouse models. These studies were primarily focused transcriptional changes affecting steady-state overall levels using microarray based approaches. A missing component, however, has been study...

With the development of Internet Things (IoT) and birth various new IoT devices, capacity massive devices is facing challenges. Fortunately, edge computing can optimize problems such as delay connectivity by offloading part computational tasks to nodes close data source. Using this feature, save more resources while still maintaining quality service. However, since computation decisions concern joint complex resource management, we use multiple Deep Reinforcement Learning (DRL) agents...

Kubernetes (k8s) has the potential to merge distributed edge and cloud but lacks a scheduling framework specifically for edge-cloud systems. Besides, hierarchical distribution of heterogeneous resources complex dependencies among requests make modeling k8s-oriented systems particularly sophisticated. In this paper, we introduce KaiS, learning-based such improve long-term throughput rate request processing. First, design coordinated multi-agent actor-critic algorithm cater decentralized...

Exonization of Alu elements is a major mechanism for birth new exons in primate genomes. Prior analyses expressed sequence tags show that almost all Alu-derived are alternatively spliced, and the vast majority these have low transcript inclusion levels. In this work, we provide genomic experimental evidence diverse splicing patterns exonized human tissues. Using Exon array data 330 11 tissues detailed RT-PCR 38 exons, some constitutively spliced broad range tissues, display strong...

Abstract The rapid accumulation of clinical RNA-seq data sets has provided the opportunity to associate mRNA isoform variations outcomes. Here we report a statistical method SURVIV ( Surv ival analysis I soform V ariation), designed for identifying variation associated with patient survival time. A unique feature and major strength is that it models measurement uncertainty ratio in data. Simulation studies suggest outperforms conventional Cox regression analysis, especially modest sequencing...

Abstract Metastatic colonization is an ominous feature of cancer progression. Recent studies have established the importance pre-mRNA alternative splicing (AS) in biology. However, little known about transcriptome-wide landscape AS associated with metastatic colonization. Both vitro and vivo models were utilized to study regulation metastasis. Transcriptome profiling prostate cells derivatives crossing or barriers metastasis revealed factors significant gene expression changes These include...

Learning-based visual odometry (VO) algorithms achieve remarkable performance on common static scenes, benefiting from high-capacity models and massive annotated data, but tend to fail in dynamic, populated environments. Semantic segmentation is largely used discard dynamic associations before estimating camera motions at the cost of discarding features hard scale up unseen categories. In this paper, we leverage mutual dependence between ego-motion motion show that both can be jointly...

We describe a method, microarray analysis of differential splicing (MADS), for discovery alternative from exon-tiling data. MADS incorporates series low-level algorithms motivated by the "probe-rich" design exon arrays, including background correction, iterative probe selection, and removal sequence-specific cross-hybridization to off-target transcripts. used analyze Affymetrix Exon 1.0 array data on mouse neuroblastoma cell line after shRNA-mediated knockdown factor polypyrimidine tract...

A-to-I RNA editing is an important step in processing which specific adenosines some molecules are post-transcriptionally modified to inosines. has emerged as a widespread mechanism for generating transcriptome diversity. However, there remain significant knowledge gaps about the variation and function of editing. In order determine influence genetic on editing, we integrate genomic transcriptomic data from 445 human lymphoblastoid cell lines by combining QTL (edQTL) analysis with...

Autonomous robotic surgery has seen significant progression over the last decade with aims of reducing surgeon fatigue, improving procedural consistency, and perhaps one day take itself. However, automation not been applied to critical surgical task controlling tissue blood vessel bleeding-known as hemostasis. The hemostasis covers a spectrum bleeding sources range velocity, trajectory, volume. In an extreme case, un-controlled fills field flowing blood. this work, we present first,...

ABSTRACT Both tryptophan (Trp) and tyrosine (Tyr) play a significant role in the formation of volatile compounds processes such as food processing cigarette combustion. While metabolic pathways these amino acids have been extensively studied, their pyrolysis under cigarette‐like conditions remains poorly understood. This study investigates behavior Trp Tyr mimicking combustion using online pyrolysis‐gas chromatography/mass spectrometry. were subjected to analyzed Key findings reveal: (1)...

CPEB is a sequence-specific RNA binding protein that promotes polyadenylation-induced translation in early development, during cell cycle progression and cellular senescence, following neuronal synapse stimulation. It controls polyadenylation through other interacting molecules, most notably the poly(A) polymerase Gld2, deadenylating enzyme PARN, eIF4E-binding Maskin. Here, we report shuttles between nucleus cytoplasm its export occurs via CRM1-dependent pathway. In of Xenopus oocytes,...

Alternative pre-mRNA splicing is a prevalent mechanism in mammals that promotes proteomic diversity, including expression of cell-type specific protein isoforms. We characterized role for RBM38 (RNPC1) regulation alternative during late erythroid differentiation. used an Affymetrix human exon junction (HJAY) microarray to identify panel RBM38-regulated alternatively spliced transcripts. Using databases, we noted high levels CD71+ cells and thus chose examine differentiation hematopoietic...