Dataset Information

Quantifying splice-site usage: a simple yet powerful approach to analyze splicing.

ABSTRACT: RNA splicing, and variations in this process referred to as alternative splicing, are critical aspects of gene regulation in eukaryotes. From environmental responses in plants to being a primary link between genetic variation and disease in humans, splicing differences confer extensive phenotypic changes across diverse organisms (1-3). Regulation of splicing occurs through differential selection of splice sites in a splicing reaction, which results in variation in the abundance of isoforms and/or splicing events. However, genomic determinants that influence splice-site selection remain largely unknown. While traditional approaches for analyzing splicing rely on quantifying variant transcripts (i.e. isoforms) or splicing events (i.e. intron retention, exon skipping etc.) (4), recent approaches focus on analyzing complex/mutually exclusive splicing patterns (5-8). However, none of these approaches explicitly measure individual splice-site usage, which can provide valuable information about splice-site choice and its regulation. Here, we present a simple approach to quantify the empirical usage of individual splice sites reflecting their strength, which determines their selection in a splicing reaction. Splice-site strength/usage, as a quantitative phenotype, allows us to directly link genetic variation with usage of individual splice-sites. We demonstrate the power of this approach in defining the genomic determinants of splice-site choice through GWAS. Our pilot analysis with more than a thousand splice sites hints that sequence divergence in cis rather than trans is associated with variations in splicing among accessions of Arabidopsis thaliana. This approach allows deciphering principles of splicing and has broad implications from agriculture to medicine.

SUBMITTER: Dent CI

PROVIDER: S-EPMC8121094 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundCommonly, several traits are assessed in agronomic experiments to better understand the factors under study. However, it is also common to see that even when several traits are available, researchers opt to follow the easiest way by applying univariate analyses and post-hoc tests for mean comparison for each trait, which arouses the hypothesis that the benefits of a multi-trait framework analysis may have not been fully exploited in this area.ResultsIn this paper, we extended the theoretical foundations of the multi-trait genotype-ideotype distance index (MGIDI) to analyze multivariate data either in simple experiments (e.g., one-way layout with few treatments and traits) or complex experiments (e.g., with a factorial treatment structure). We proposed an optional weighting process that makes the ranking of treatments that stands out in traits with higher weights more likely. Its application is illustrated using (1) simulated data and (2) real data from a strawberry experiment that aims to select better factor combinations (namely, cultivar, transplant origin, and substrate mixture) based on the desired performance of 22 phenological, productive, physiological, and qualitative traits. Our results show that most of the strawberry traits are influenced by the cultivar, transplant origin, cultivation substrates, as well as by the interaction between cultivar and transplant origin. The MGIDI ranked the Albion cultivar originated from Imported transplants and the Camarosa cultivar originated from National transplants as the better factor combinations. The substrates with burned rice husk as the main component (70%) showed satisfactory physical proprieties, providing higher water use efficiency. The strengths and weakness view provided by the MGIDI revealed that looking for an ideal treatment should direct the efforts on increasing fruit production of Albion transplants from Imported origin. On the other hand, this treatment has strengths related to productive precocity, total soluble solids, and flesh firmness.ConclusionsOverall, this study opens the door to the use of MGIDI beyond the plant breeding context, providing a unique, practical, robust, and easy-to-handle multi-trait-based framework to analyze multivariate data. There is an exciting possibility for this to open up new avenues of research, mainly because using the MGIDI in future studies will dramatically reduce the number of tables/figures needed, serving as a powerful tool to guide researchers toward better treatment recommendations.

Dataset Information

Quantifying splice-site usage: a simple yet powerful approach to analyze splicing.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets