title: TRIC: an automated alignment strategy for reproducible protein quantification in targeted proteomics.
abstract: Next-generation mass spectrometric (MS) techniques such as SWATH-MS have substantially increased the throughput and reproducibility of proteomic analysis, but ensuring consistent quantification of thousands of peptide analytes across multiple liquid chromatography-tandem MS (LC-MS/MS) runs remains a challenging and laborious manual process. To produce highly consistent and quantitatively accurate proteomics data matrices in an automated fashion, we developed TRIC (http://proteomics.ethz.ch/tric/), a software tool that utilizes fragment-ion data to perform cross-run alignment, consistent peak-picking and quantification for high-throughput targeted proteomics. TRIC reduced the identification error compared to a state-of-the-art SWATH-MS analysis without alignment by more than threefold at constant recall while correcting for highly nonlinear chromatographic effects. On a pulsed-SILAC experiment performed on human induced pluripotent stem cells, TRIC was able to automatically align and quantify thousands of light and heavy isotopic peak groups. Thus, TRIC fills a gap in the pipeline for automated analysis of massively parallel targeted proteomics data sets.
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.|Department of Genetics, Stanford University, Stanford, California, USA.
authors.forename: Hannes L
authors.identifier: 0000-0003-0990-7488
authors.initials: HL
authors.lastname: Röst
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Yansheng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: D'Agostino
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Zanella
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.|Institute for Immunology, University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany.
authors.forename: Pedro
authors.identifier: 0000-0002-9052-1824
authors.initials: P
authors.lastname: Navarro
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.|PhD Program in Systems Biology, University of Zurich and ETH Zurich, Zurich, Switzerland.
authors.forename: George
authors.identifier: 0000-0002-1655-6789
authors.initials: G
authors.lastname: Rosenberger
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Ben C
authors.initials: BC
authors.lastname: Collins
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Gillet
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.|Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Testa
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.|S3IT, University of Zurich, Zurich, Switzerland.
authors.forename: Lars
authors.identifier: 0000-0001-9885-9312
authors.initials: L
authors.lastname: Malmström
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.|Faculty of Science, University of Zurich, Zurich, Switzerland.
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
mesh_terms: D000465:Algorithms; D001330:Electronic Data Processing / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry; D010455:Peptides / Q000032:analysis* / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000378:metabolism; D011498:Protein Precursors / Q000032:analysis / Q000378:metabolism; D059748:Proteolysis; D040901:Proteomics / Q000295:instrumentation / Q000379:methods*; D015203:Reproducibility of Results; D016415:Sequence Alignment / Q000295:instrumentation / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000295:instrumentation / Q000379:methods*; D012984:Software; D013297:Streptococcus pyogenes / Q000378:metabolism
chemical_list: D010455:Peptides; D011498:Protein Precursors