Kahraman, Abdullah
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CanIsoNet: a database to study the functional impact of isoform switching events in diseases
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.
IsoAligner. Dynamic mapping of amino acid positions across protein isoforms
Aligning protein isoform sequences is often performed in cancer diagnostics to homogenise mutation annotations from different diagnostic assays. However, most alignment tools are fitted for homologous sequences, leading often to alignments of non-identical exonic regions. Here, we present the interactive alignment webservice IsoAligner for exact mapping of exonic protein subsequences. The tool uses a customized Needleman-Wunsch algorithm including an open gap penalty combined with a gene-specific minimal exon length function and dynamically adjustable parameters. As an input, IsoAligner accepts either various gene/transcript/protein IDs from different databases (Ensembl, UniProt, RefSeq) or raw amino acid sequences. The output of IsoAligner consists of pairwise alignments and a table of mapped amino acid positions between the canonical or supplied isoform IDs and all alternative isoforms. IsoAligner’s human isoform library comprises of over 1.3 million IDs mapped on over 120,000 protein sequences. IsoAligner, is a fast and interactive alignment tool for retrieving amino acids positions between different protein isoforms. Its application will allow diagnostic and precision medicine labs to detect inconsistent variant annotations between different assays and databases. Availability: This tool is available as a Webservice on www.isoaligner.org. A REST API is available for programmatic access. The source code for both services can be found at https://github.com/mtp-usz/IsoAligner.