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857 results for “alternative splicing;”
Database of human alternative 5' and 3' splice sites
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Data from: Comparative transcriptomics uncovers alternative splicing changes and signatures of selection from maize improvement
Background: Alternative splicing (AS) is an important regulatory mechanism that greatly contributes to eukaryotic transcriptome diversity. A substantial amount of evidence has demonstrated that AS complexity is relevant to eukaryotic evolution, development, adaptation, and complexity. In this study, six teosinte and ten maize transcriptomes were sequenced to analyze AS changes and signatures of selection in maize domestication and improvement. Results In maize and teosinte, 13,593 highly conserved genes, including 12,030 multiexonic genes, were detected. By identifying AS isoforms from mutliexonic genes, we found that AS types were not significantly different between maize and teosinte. In addition, the two main AS types (intron retention and alternative acceptor) contributed to more than 60% of the AS events in the two species, but the average unique AS events per each alternatively spliced gene in maize (4.12) was higher than that in teosinte (2.26). Moreover, 94 genes generating 98 retained introns with transposable element (TE) sequences were detected in maize, which is far more than 9 retained introns with TEs detected in teosinte. This indicates that TE insertion might be an important mechanism for intron retention in maize. Additionally, the AS levels of 3864 genes were significantly different between maize and teosinte. Of these, 151 AS level-altered genes that are involved in transcriptional regulation and in stress responses are located in regions that have been targets of selection during maize improvement. These genes were inferred to be putatively improved genes. Conclusions We suggest that both maize and teosinte share similar AS mechanisms, but more genes have increased AS complexity during domestication from teosinte to maize. Importantly, a subset of AS level-increased genes that encode transcription factors and stress-responsive proteins may have been selected during maize improvement.
Characterisation of alternative splicing events induced through alterations in spliceosome genes in breast cancer
<p>Additional data for supplementary tables in project 2 report </p> <p>Supplementary data for Project 2 entitled : "Characterisation of alternative splicing events induced through alterations in spliceosome genes in breast cancer"</p>
Paired datasets to study alternative splicing regulation by individual RNA-binding proteins
<p>This project stores datasets generated to study the regulation of alternative splicing using deep learning models (e.g., SpliceAI). In particular, these datasets were used to perform ablation studies (sequence perturbations at motif locations) to evaluate their effects on the deep learning model.</p> <p><span>I </span><span>used public RNA-Seq data from the ENCODE consortium to identify exons sensitive to the knockdown of RNA-binding proteins (RBPs). The idea is that exons sensitive to RBP knockdowns are more likely to be directly or indirectly regulated by such RBPs, hence providing hints on their regulation mechanisms. Importantly,</span><span> I </span><span>also generated paired control exons, which were not alternatively spliced upon RBP knockdown but have similar GC composition and length compared to the knockdown-sensitive exons (target exon and surrounding introns). These control sets were generated to account for potential confounding factors of gene architecture features and, therefore, focus only on RBP binding motifs and their regulatory logic.</span></p> <p><strong>Information about the files</strong></p> <p>After uncompressing the 'paired_dataset.tar.gz' file, a directory with multiple files will be created with the following structure:</p> <ul> <li><em>0_rMATS_ES_events.tsv.gz</em><em>: </em>Summary tables of differential splicing analysis, with deltaPSI estimates referring to Ctrl - Knockdown groups. Important columns: 'target_coordinates' refers to the 1-based coordinates of the alternatively spliced exon, and 'group' indicates the individual knockdown experiments where the exon was observed to be alternatively spliced.</li> <li><em>0_rMATs_ES_non_changing_events.tsv.gz:</em> Summary tables of differential splicing analysis, but in this case, contains all non-changing events (dPSI < |0.025|).</li> <li> <p><em>1_KD_exons_dPSI0.1.tsv.gz:</em> Table with knockdown-sensitive exons along with values for gene architecture features along the exon triplet (exon upstream, intron upstream, cassette exon, intron downstream exon downstream).</p> </li> <li> <p><em>1_Ctrl_exons_dPSI0.025.tsv.gz:</em> Same as '1_KD_exons_dPSI0.1.tsv.gz', but for all non-changing events.</p> </li> <li> <p><em><strong>2_paired_datasets.tsv.gz:</strong></em> Paired datasets in tidy format, where Knockdown-sensitive exons and their Control pairs come in consecutive lines. The 'rbp_name' column refers to the individual knockdown experiment where that exon was observed.</p> </li> <li><em>2_paired_datasets_negative_dPSI.tsv.gz, 2_paired_datasets_positive_dPSI.tsv.gz:</em> Same as '2_paired_datasets.tsv.gz', but knockdown-sensitive exons are split according to the direction of dPSI observed in the RNA-Seq data (along with the respective control pair).</li> <li><em>2_paired_datasets_individualRBPs</em>: This folder contains the paired datasets in wide format, where a single line contains both the knockdown-sensitive and control pair. In addition, each paired dataset (knockdown of individual RBP) is written in a separate file.</li> </ul> <div><strong>Details of the sh knockdown RNA-Seq analysis</strong></div> <div>Because in the ENCODE study (Van Nostrand E.L. et al., 2020), authors analyzed knockdown RNA Seq data using an older version of the human genome (hg19) along with old genome annotations (GENCODE v19), I reanalyzed ENCODE data aligned to the hg38 genome build. I used rMATS v4.1.2 on each RBP knockdown experiment to detect differentially spliced events between the two knockdown replicates vs the two control replicates. rMATS was run with GENCODE annotations v44 and specifically tweaked with <em>--cstat 0.05</em>. <div> </div> <div>Significant knockdown-sensitive events were identified with a deltaPSI > |0.1|, using a False Discovery Rate cutoff of 0.05. Non-changing events, assumed as knockdown-agnostic controls, were defined as those exhibiting negligible deltaPSI variation (< |0.025|). To ensure the high quality of the exon sets, further analytical steps were performed. First, I applied a read coverage filter, by retaining events where the median coverage across replicates per condition for the isoform with more read counts was higher than 7. Then, I exclusively focused on exon skipping events in protein-coding genes, and filtered out unannotated exons (pseudoexons) as well as first or last exons of genes. In addition, I excluded duplicate exon skipping events by picking the transcript with the highest biological importance (based on the presence of transcript flags such as MANE selected, CCDS, or APPRIS). A total of 15,235 events were detected across all RBP knockdown experiments (N=72, splicing-associated RBPs with data available for the HepG2 cell line), covering 6,659 unique exons.</div> </div> <div> <div> </div> </div>
rMATS analysis of alternative splicing events in a mouse model of environmental liver disease
<p>rMATS (https://rnaseq-mats.sourceforge.io/) was used to identify differential alternative splicing events (ASEs) corresponding to all five major types of AS patterns, <em>i.e</em>., skipped exon (SE), mutually exclusive exons (MXE), alternative 3’ splice site (A3SS), alternative 5’ splice site (A5SS), and retained intron (RI), in the HFD-fed mouse livers exposed to Ar1260, PCB126, or Ar1260 + PCB126 co-exposure compared to vehicle control This dataset identifies differential ASEs corresponding to all five major types of AS patterns [<em>i.e.,</em> skipped exon (SE), mutually exclusive exons (MXE), alternative 3’ splice site (A3’SS), alternative 5’ splice site (A5’SS), and retained intron (RI)], between Ar1260, PCB126, and Ar1260 + PCB126-exposed samples and vehicle control. For each ASE, the estimation of the alternatively spliced region usage is defined as percent-spliced in (ψ or PSI). Each comparison was made to identify differential ASEs with an associated change in exon usage (∆ψ). Differential ASEs were detected with an FDR of <0.05 and |∆ψ| of≥5%. The difference in the proportion of the two isoforms of the transcript was expressed as the change in mean percentage spliced-inform included (mean ∆ψ).</p>
Data from: Comparative transcriptomics uncovers alternative splicing changes and signatures of selection from maize improvement
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Differentially expressed alternatively spliced genes associated with carcass and meat traits in Nelore cattle
<p>Quality control report from Qualimap 2.2.1. Basic statistics of the alignment (number of reads, coverage, GC-content, junction detection, etc.) were summarized. Quality control was performed with RNA-seq data from muscle tissue of Nelore Cattle. Transcript data were used to identify genes for which alternatively spliced transcripts were differentially expressed in ribeye muscle tissue between Nelore cattle that differed in their ribeye muscle area (REA) or intramuscular fat content (IF).</p>
Data from: Genome-wide analysis of alternative splicing in Zea mays: landscape and genetic regulation
Alternative splicing enhances transcriptome diversity in all eukaryotes and plays a role in plant tissue identity and stress adaptation. To catalog new maize (Zea mays) transcripts and identify genomic loci that regulate alternative splicing, we analyzed over 90 RNA-seq libraries from maize inbred lines B73 and Mo17, as well as Syn10 doubled haploid lines (progenies from B73 × Mo17). Transcript discovery was augmented with publicly available data from 14 maize tissues, expanding the maize transcriptome by more than 30,000 and increasing the percentage of intron-containing genes that undergo alternative splicing to 40%. These newly identified transcripts greatly increase the diversity of the maize proteome, sometimes coding for entirely different proteins compared with their most similar annotated isoform. In addition to increasing proteome diversity, many genes encoding novel transcripts gained an additional layer of regulation by microRNAs, often in a tissue-specific manner. We also demonstrate that the majority of genotype-specific alternative splicing can be genetically mapped, with cis-acting quantitative trait loci (QTLs) predominating. A large number of trans-acting QTLs were also apparent, with nearly half located in regions not shown to contain genes associated with splicing. Taken together, these results highlight the currently underappreciated role that alternative splicing plays in tissue identity and genotypic variation in maize.
Data from: Transcriptome analysis indicates considerable divergence in alternative splicing between duplicated genes in Arabidopsis thaliana
Gene and genome duplication events have created a large number of new genes in plants that can diverge by evolving new expression profiles and functions (neofunctionalization) or dividing extant ones (subfunctionalization). Alternative splicing (AS) generates multiple types of mRNA from a single type of pre-mRNA by differential intron splicing. It can result in new protein isoforms or down-regulation of gene expression by transcript decay. Using RNA-seq we investigated the degree to which alternative splicing patterns are conserved between duplicated genes in Arabidopsis thaliana. Our results revealed that 30% of AS events in alpha whole genome duplicates, and 33% of AS events in tandem duplicates, are qualitatively conserved within leaf tissue. Loss of ancestral splice forms, as well as asymmetric gain of new splice forms, may account for this divergence. Conserved events had different frequencies, as only 31% of shared AS events in alpha whole genome duplicates and 41% of shared AS events in tandem duplicates had similar frequencies in both paralogs, indicating considerable quantitative divergence. Analysis of published RNA-seq data from nonsense mediated decay (NMD) mutants indicated that 85% of alpha whole genome duplicates and 89% of tandem duplicates have diverged in their AS-induced NMD. Our results indicate that alternative splicing shows a high degree of divergence between paralogs such that qualitatively conserved alternative splicing events tend to have quantitative divergence. Divergence in AS patterns between duplicates may be a mechanism of regulating expression level divergence.
Datasets for the paper "Regulation of endocrine cell alternative splicing revealed by single-cell RNA sequencing in type 2 diabetes pathogenesis."
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Data from: Alternative splicing substantially diversifies the transcriptome during early photomorphogenesis and correlates with the energy availability in Arabidopsis
Plants use light as source of energy and information to detect diurnal rhythms and seasonal changes. Sensing changing light conditions is critical to adjust plant metabolism and to initiate developmental transitions. Here we analyzed transcriptome-wide alterations in gene expression and alternative splicing (AS) of etiolated seedlings undergoing photomorphogenesis upon exposure to blue, red, or white light. Our analysis revealed massive transcriptome reprograming as reflected by differential expression of ~20% of all genes and changes in several hundred AS events. For more than 60% of all regulated AS events, light promoted the production of a presumably protein-coding variant at the expense of an mRNA with nonsense-mediated decay-triggering features. Accordingly, AS of the putative splicing factor REDUCED RED-LIGHT RESPONSES IN CRY1CRY2 BACKGROUND 1 (RRC1), previously identified as a red light signaling component, was shifted to the functional variant under light. Downstream analyses of candidate AS events pointed at a role of photoreceptor signaling only in monochromatic but not in white light. Furthermore, we demonstrated similar AS changes upon light exposure and exogenous sugar supply, with a critical involvement of kinase signaling. We propose that AS is an integration point of signaling pathways that sense and transmit information regarding the energy availability in plants.
Alternatively spliced exon regulates context-dependent MEF2D higher-order assembly during myogenesis
<p>Molecular dynamics data on four MEF2D beta-domain peptide constructs.</p>
BRACE: A Bayesian-based dimension reduction approach for single-cell alternative splicing analysis
<p>Datasets to demonstrate the utility of our BRACE method.</p>
Splitpea: quantifying protein interaction network rewiring changes due to alternative splicing in cancer
<p>This serves as the supplementary data repo for the paper, <em><a href="https://doi.org/10.1101/2023.09.04.556262">Splitpea: quantifying protein interaction network rewiring changes due to alternative splicing in cancer</a>. </em></p> <p>The file structure is as follows:</p> <ul> <li>Splitpea rewired PPI networks for individual patient samples (files ending in `patient-rewired-networks.zip`). The networks are stored as dat files, which are tab delimited with one row per edge. Gene ids are reported as entrez id, the edge weights determine the directionality of the interaction (positive weights are potential gains, negative weights are edges likely lost). Chaos edges can have a positive or negative weight but will be indicated by a boolean value in the `chaos` column.</li> <li>The consensus networks (files ending in `consensus_networks`) are separated into two networks one for positive edges and one for negative edges present in at least 80% of tumor samples. These files are tab delimited files with one row per edge in the corresponding undirected weighted network. The following columns are included: <ul> <li>node1, node2: genes incident on the edge as entrez gene IDs</li> <li>mean_weight: average weight of edge across networks (where edge is present) used to build the consensus</li> <li>total_weight: sum of weights across networks (where edge is present) used to build the consensus</li> <li>num_graphs: # of networks where edge was present</li> <li>prop_graphs: # of networks where edge was present / total # of networks used to build the consensus</li> </ul> </li> <li>IRIS.zip: Splicing matrix spliced exon files from IRIS (Pan et al. <a href="https://doi.org/10.1073/pnas.2221116120">https://doi.org/10.1073/pnas.2221116120</a>). These are the initial inputs for the Splitpea run described in the paper.</li> <li>BRCA-psi.zip: precalculated PSI values for breast cancer samples as described in the paper</li> <li>PAAD-psi.zip: precalculated PSI values for pancreatic cancer samples as described in the paper</li> <li>*-centralities.zip: precalculated centralities for each patient network</li> <li>*-pickle.zip: network representations as pickle files</li> </ul>
Data from: Alternative splicing substantially diversifies the transcriptome during early photomorphogenesis and correlates with the energy availability in Arabidopsis
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Data from: Polypyrimidine tract-binding protein homologues from Arabidopsis are key regulators of alternative splicing with implications in fundamental developmental processes
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Data from: Genome-wide analysis of alternative splicing in Zea mays: landscape and genetic regulation
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Data from: Transcriptome analysis indicates considerable divergence in alternative splicing between duplicated genes in Arabidopsis thaliana
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Data from: Nonsense-mediated decay of alternative pre-mRNA splicing variants is a major determinant of the Arabidopsis steady state transcriptome
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Data from: Splicing factor SF3B1K700E mutant dysregulates erythroid differentiation via aberrant alternative splicing of transcription factor TAL1
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