DoChaP: the domain change presenter

Alternative RNA splicing results in multiple transcripts of the same gene, possibly encoding for different protein isoforms with different protein domains and functionalities. Whereas it is possible to manually determine the effect of a specific alternative splicing event on the domain composition of a particular encoded protein, the process requires the tedious integration of several data sources; it is therefore error prone and its implementation is not feasible for genome-wide characterization of domains affected by differential splicing. To fulfill the need for an automated solution, we developed the Domain Change Presenter (DoChaP), a web server for the visualization of the exon–domain association. DoChaP visualizes all transcripts of a given gene, the domains of the proteins that they encode, and the exons encoding each domain. The visualization enables a comparison between the transcripts and between the protein isoforms they encode for. The organization and visual presentation of the information makes the structural effect of each alternative splicing event on the protein structure easily identified. To enable a study of the conservation of the exon structure, alternative splicing, and the effect of alternative splicing on protein domains, DoChaP also facilitates an inter-species comparison of domain–exon associations. DoChaP thus provides a unique and easy-to-use visualization of the exon–domain association and its conservation between transcripts and orthologous genes and will facilitate the study of the functional effects of alternative splicing in health and disease.

[1]  Wen J. Li,et al.  Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation , 2015, Nucleic Acids Res..

[2]  David Penny,et al.  Functional and evolutionary analysis of alternatively spliced genes is consistent with an early eukaryotic origin of alternative splicing , 2007, BMC Evolutionary Biology.

[3]  Silvio C. E. Tosatto,et al.  The Pfam protein families database in 2019 , 2018, Nucleic Acids Res..

[4]  Silvio C. E. Tosatto,et al.  InterPro in 2019: improving coverage, classification and access to protein sequence annotations , 2018, Nucleic Acids Res..

[5]  Narmada Thanki,et al.  CDD/SPARCLE: the conserved domain database in 2020 , 2019, Nucleic Acids Res..

[6]  Gil Ast,et al.  How did alternative splicing evolve? , 2004, Nature Reviews Genetics.

[7]  Mattia D'Antonio,et al.  ASPicDB: a database web tool for alternative splicing analysis. , 2015, Methods in molecular biology.

[8]  Bartek Wilczynski,et al.  Biopython: freely available Python tools for computational molecular biology and bioinformatics , 2009, Bioinform..

[9]  Alex Bateman,et al.  Tissue-Specific Splicing of Disordered Segments that Embed Binding Motifs Rewires Protein Interaction Networks , 2012, Molecular cell.

[10]  Astrid Gall,et al.  Ensembl 2020 , 2019, Nucleic Acids Res..

[11]  Tom Misteli,et al.  RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E) , 2011, Nature.

[12]  C. Chothia,et al.  Evolution of the Protein Repertoire , 2003, Science.

[13]  E. Oláh,et al.  Emerging roles of BRCA1 alternative splicing , 2003, Molecular pathology : MP.

[14]  B. Henderson,et al.  The BRCA1 RING and BRCT Domains Cooperate in Targeting BRCA1 to Ionizing Radiation-induced Nuclear Foci* , 2005, Journal of Biological Chemistry.

[15]  Franziska Meier,et al.  ProSAS: a database for analyzing alternative splicing in the context of protein structures , 2007, Nucleic Acids Res..

[16]  Wes McKinney,et al.  Data Structures for Statistical Computing in Python , 2010, SciPy.

[17]  Erin Beck,et al.  TIGRFAMs and Genome Properties in 2013 , 2012, Nucleic Acids Res..

[18]  Ashwini Bhasi,et al.  ExDom: an integrated database for comparative analysis of the exon–intron structures of protein domains in eukaryotes , 2008, Nucleic Acids Res..

[19]  R. Aebersold,et al.  Impact of Alternative Splicing on the Human Proteome , 2017, Cell Reports.

[20]  Zheng Congyi,et al.  Alternative splicing of breast cancer associated gene BRCA1 from breast cancer cell line. , 2007, Journal of biochemistry and molecular biology.

[21]  Adam Godzik,et al.  The Functional Impact of Alternative Splicing in Cancer. , 2017, Cell reports.

[22]  Arfa Mehmood,et al.  Systematic evaluation of differential splicing tools for RNA-seq studies , 2019, Briefings Bioinform..

[23]  International Human Genome Sequencing Consortium.  Initial sequencing and analysis of the human genome , 2001, Nature.

[24]  Steven E. Bayer,et al.  A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. , 1994, Science.

[25]  Peer Bork,et al.  20 years of the SMART protein domain annotation resource , 2017, Nucleic Acids Res..

[26]  Gloria M. Sheynkman,et al.  Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing , 2016, Cell.

[27]  R. Jensen,et al.  BRCA1-No Matter How You Splice It. , 2019, Cancer research.

[28]  Syed Haider,et al.  Ensembl BioMarts: a hub for data retrieval across taxonomic space , 2011, Database J. Biol. Databases Curation.

[29]  A. Porgador,et al.  Expression of NKp46 Splice Variants in Nasal Lavage Following Respiratory Viral Infection: Domain 1-Negative Isoforms Predominate and Manifest Higher Activity , 2017, Front. Immunol..

[30]  Z. Xiping,et al.  A summary of relationships between alternative splicing and breast cancer. , 2017, Oncotarget.