IsoTV: processing and visualizing functional features of translated transcript isoforms

Abstract

Summary Despite the continuous discovery of new transcript isoforms, fueled by the recent increase in accessibility and accuracy of long-read RNA sequencing data, functional differences between isoforms originating from the same gene often remain obscure. To address this issue and enable researchers to assess potential functional consequences of transcript isoform variation on the proteome, we developed IsoTV. IsoTV is a versatile pipeline to process, predict, and visualize the functional features of translated transcript isoforms. Attributes such as gene and isoform expression, transcript composition, and functional features are summarized in an easy-to-interpret visualization. IsoTV is able to analyze a variety of data types from all eukaryotic organisms, including short- and long-read RNA-seq data. Using Oxford Nanopore long read data, we demonstrate that IsoTV facilitates the understanding of potential protein isoform function in different cancer cell types. Availability IsoTV is available at https://github.molgen.mpg.de/MayerGroup/IsoTV, with the corresponding documentation at https://isotv.readthedocs.io/. Supplementary information Supplementary data are available at Bioinformatics online.

Uncovering the dynamics and consequences of RNA isoform changes during neuronal differentiation

“…Domain changes are of particular interest since they can directly alter protein functions. We therefore investigated the impact of transcript isoform changes on the protein encoding potential in more detail using the isoTV tool that we recently developed to visualize effects of RNA isoform changes on the protein sequence and post translational modification (Annaldasula et al, 2021 ). For instance, in case of PFN2 , isoTV predicted that the change in the expression of the two main RNA isoforms PFN2a and PFN2b (Fig.…”

Biosurfer for systematic tracking of regulatory mechanisms leading to protein isoform diversity

“…Our first version of Biosurfer proposes a new framework for detailed comparison of protein isoforms, a first step towards inferring function. Further versions of this tool could map functional elements, such as structural domains, active sites, post-translationally modified sites, or protein interactions, onto the altered protein regions, similar to the functionality of tappAS, isoTV, and DIGGER, as well as other tools (de la Fuente et al 2020; Annaldasula et al 2021; Louadi et al 2021). Furthermore, given the link between genomic coordinates and effects on protein isoforms, Biosurfer could capture the impact of coding or splice-modifying genetic variants as carried through the lens of complex transcript and protein variations, which might increase the accuracy of predicted genetic effects in ancestry- or patient-specific populations (Rivas et al 2015)(Cummings et al 2017)(Yamaguchi et al 2022)(Glinos et al 2022).…”

“…To characterize how AS impacts protein sequence, several bioinformatic tools and databases have been developed, such as VastDB, ASPicDB, ExonOntology, and DIGGER (Martelli et al 2011; Tapial et al 2017; Tranchevent et al 2017; Louadi et al 2021). Tools such as tappAS and IsoTV annotate how protein isoform sequence and potential functional differences (de la Fuente et al 2020; Annaldasula et al 2021). For example, tappAS is a Java application for quantifying differential isoform usage but also to functionally annotate such isoforms, using the module IsoAnnot (de la Fuente et al 2020).…”

Nanoblot: an R-package for visualization of RNA isoforms from long-read RNA-sequencing data

“…Another common approach is assigning each transcript to a discrete isoform. Tools such as IsoTV ( Annaldasula et al 2021 ) and Swan toolkit ( Reese and Mortazavi 2021 ) automate this process and help create intuitive visualizations of isoforms. However, this requires detailed annotation of the host genome and assigns reads to distinct groups.…”