2014BioinformaticsRequires access

TAPAS: tools to assist the targeted protein quantification of human alternative splice variants

Jae‐Seong Yang, Eduard Sabidó, Luís Serrano, Christina Kiel

Open publisher page 1 citations

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.

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Available 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.

Key concepts: splice, Alternative splicing, Proteome, Computational biology, Peptide, Gene isoform, Set (abstract data type), Biology

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