TAPAS: tools to assist the targeted protein quantification of human alternative splice variants
Jae‐Seong Yang, Eduard Sabidó, Luís Serrano, Christina Kiel
Abstract
Jae‐Seong Yang, Eduard Sabidó, Luís Serrano, Christina Kiel
Abstract
MOTIVATION: In proteomes of higher eukaryotes, many alternative splice variants can only be detected by their shared peptides. This makes it highly challenging to use peptide-centric mass spectrometry to distinguish and to quantify protein isoforms resulting from alternative splicing events. RESULTS: We have developed two complementary algorithms based on linear mathematical models to efficiently compute a minimal set of shared and unique peptides needed to quantify a set of isoforms and splice variants. Further, we developed a statistical method to estimate the splice variant abundances based on stable isotope labeled peptide quantities. The algorithms and databases are integrated in a web-based tool, and we have experimentally tested the limits of our quantification method using spiked proteins and cell extracts. AVAILABILITY AND IMPLEMENTATION: The TAPAS server is available at URL http://davinci.crg.es/tapas/. CONTACT: luis.serrano@crg.eu or christina.kiel@crg.eu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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MOTIVATION: In proteomes of higher eukaryotes, many alternative splice variants can only be detected by their shared peptides. This makes it highly challenging to use peptide-centric mass spectrometry to distinguish and to quantify protein isoforms resulting from alternative splicing events. RESULTS: We have developed two complementary algorithms based on linear mathematical models to efficiently compute a minimal set of shared and unique peptides needed to quantify a set of isoforms and splice variants. Further, we developed a statistical method to estimate the splice variant abundances based on stable isotope labeled peptide quantities. The algorithms and databases are integrated in a web-based tool, and we have experimentally tested the limits of our quantification method using spiked proteins and cell extracts. AVAILABILITY AND IMPLEMENTATION: The TAPAS server is available at URL http://davinci.crg.es/tapas/. CONTACT: luis.serrano@crg.eu or christina.kiel@crg.eu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Key concepts: splice, Alternative splicing, Proteome, Computational biology, Peptide, Gene isoform, Set (abstract data type), Biology