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CanIsoNet: a database to study the functional impact of isoform switching events in diseases
Tülay Karakulak1,2,3, Damian Szklarczyk1,3, Cemil Can Saylan4
1Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, Zurich, 8057, Switzerland.
Motivation:
Alternative splicing, as an essential regulatory mechanism in normal mammalian cells, is frequently disturbed in cancer and other diseases. Switches in the expression of most dominant alternative isoforms can alter protein interaction networks of associated genes giving rise to disease and disease progression. Here, we present CanIsoNet, a database to view, browse and search isoform switching events in diseases. CanIsoNet is the first webserver that incorporates isoform expression data with STRING interaction networks and ClinVar annotations to predict the pathogenic impact of isoform switching events in various diseases.
Results:
Data in CanIsoNet can be browsed by disease or searched by genes or isoforms in annotation-rich data tables. Various annotations for 11 811 isoforms and 14 357 unique isoform switching events across 31 different disease types are available. The network density score for each disease-specific isoform, PFAM domain IDs of disrupted interactions, domain structure visualization of transcripts and expression data of switched isoforms for each sample is given. Additionally, the genes annotated in ClinVar are highlighted in interactive interaction networks.
Availability And Implementation:
CanIsoNet is freely available at https://www.caniso.net. The source codes can be found under a Creative Common License at https://github.com/kahramanlab/CanIsoNet_Web.
Supplementary Information:
Supplementary data are available at Bioinformatics Advances online.
Insights
CanIsoNet is a new database that tracks changes in alternative splicing (isoform switching) linked to diseases. It integrates gene expression, protein interactions, and clinical data to predict the impact of these switches on disease progression.
Area of Science:
- Genomics
- Bioinformatics
- Molecular Biology
Background:
- Alternative splicing is a key regulatory mechanism in mammalian cells.
- Dysregulation of alternative splicing is implicated in cancer and other diseases.
- Isoform switching can alter protein interaction networks, driving disease development.
Purpose of the Study:
- To introduce CanIsoNet, a novel database for exploring isoform switching events in diseases.
- To provide a platform for viewing, browsing, and searching disease-associated isoform data.
- To integrate diverse biological datasets for predicting the pathogenic impact of isoform switching.
Main Methods:
- Developed CanIsoNet, a web server incorporating isoform expression data.
- Integrated STRING interaction networks and ClinVar annotations.
- Enabled browsing by disease and searching by genes or isoforms.
Main Results:
- CanIsoNet contains data for 11,811 isoforms and 14,357 isoform switching events across 31 diseases.
- Provides network density scores, PFAM domain IDs, transcript structure visualization, and sample-specific expression data.
- Highlights ClinVar-annotated genes within interactive networks.
Conclusions:
- CanIsoNet is a valuable resource for studying the role of alternative splicing in disease.
- The database facilitates the prediction of pathogenic impacts of isoform switching events.
- Enables comprehensive analysis of isoform dynamics in various disease contexts.
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