Dataset Information

Large-scale analysis of branchpoint usage across species and cell lines.

ABSTRACT: The coding sequence of each human pre-mRNA is interrupted, on average, by 11 introns that must be spliced out for proper gene expression. Each intron contains three obligate signals: a 5' splice site, a branch site, and a 3' splice site. Splice site usage has been mapped exhaustively across different species, cell types, and cellular states. In contrast, only a small fraction of branch sites have been identified even once. The few reported annotations of branch site are imprecise as reverse transcriptase skips several nucleotides while traversing a 2-5 linkage. Here, we report large-scale mapping of the branchpoints from deep sequencing data in three different species and in the SF3B1 K700E oncogenic mutant background. We have developed a novel method whereby raw lariat reads are refined by U2snRNP/pre-mRNA base-pairing models to return the largest current data set of branchpoint sequences with quality metrics. This analysis discovers novel modes of U2snRNA:pre-mRNA base-pairing conserved in yeast and provides insight into the biogenesis of intron circles. Finally, matching branch site usage with isoform selection across the extensive panel of ENCODE RNA-seq data sets offers insight into the mechanisms by which branchpoint usage drives alternative splicing.

SUBMITTER: Taggart AJ

PROVIDER: S-EPMC5378181 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Large-scale analysis of branchpoint usage across species and cell lines.

Taggart Allison J AJ Lin Chien-Ling CL Shrestha Barsha B Heintzelman Claire C Kim Seongwon S Fairbrother William G WG

Genome research 20170124 4

The coding sequence of each human pre-mRNA is interrupted, on average, by 11 introns that must be spliced out for proper gene expression. Each intron contains three obligate signals: a 5' splice site, a branch site, and a 3' splice site. Splice site usage has been mapped exhaustively across different species, cell types, and cellular states. In contrast, only a small fraction of branch sites have been identified even once. The few reported annotations of branch site are imprecise as reverse tran ...[more]

PMID: 28119336

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Project description:BackgroundDigital learning environments have become very common in the training of medical professionals, and students often use such platforms for exam preparation. Multiple choice questions (MCQs) are a common format in medical exams and are used by students to prepare for said exams.ObjectiveWe aimed to examine whether particular learning activities contributed more strongly than others to users' exam performance.MethodsWe analyzed data from users of an online platform that provides learning materials for medical students in preparation for their final exams. We analyzed whether the number of learning cards viewed and the number of MCQs taken were positively related to learning outcomes. We also examined whether viewing learning cards or answering MCQs was more effective. Finally, we tested whether taking individual notes predicted learning outcomes, and whether taking notes had an effect after controlling for the effects of learning cards and MCQs. Our analyses from the online platform Amboss are based on user activity data, which supplied the number of learning cards studied and test questions answered. We also included the number of notes from each of those 23,633 users who had studied at least 200 learning cards and had answered at least 1000 test exam questions in the 180 days before their state exam. The activity data for this analysis was collected retrospectively, using Amboss archival usage data from April 2014 to April 2017. Learning outcomes were measured using the final state exam scores that were calculated by using the answers voluntarily entered by the participants.ResultsWe found correlations between the number of cards studied (r=.22; P<.001) and the number of test questions that had been answered (r=.23; P<.001) with the percentage of correct answers in the learners' medical exams. The number of test questions answered still yielded a significant effect, even after controlling for the number of learning cards studied using a hierarchical regression analysis (?=.14; P<.001; ?R2=.017; P<.001). We found a negative interaction between the number of learning cards and MCQs, indicating that users with high scores for learning cards and MCQs had the highest exam scores. Those 8040 participants who had taken at least one note had a higher percentage of correct answers (80.94%; SD=7.44) than those who had not taken any notes (78.73%; SD=7.80; t23631=20.95; P<.001). In a stepwise regression, the number of notes the participants had taken predicted the percentage of correct answers over and above the effect of the number of learning cards studied and of the number of test questions entered in step one (?=.06; P<.001; ?R2=.004; P<.001).ConclusionsThese results show that online learning platforms are particularly helpful whenever learners engage in active elaboration in learning material, such as by answering MCQs or taking notes.

Dataset Information

Large-scale analysis of branchpoint usage across species and cell lines.

Publications

Large-scale analysis of branchpoint usage across species and cell lines.

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