Cleaning out the Litterbox of Proteomic Scientists’ Favorite Pet: Optimized Data Analysis Avoiding Trypsin Artifacts
Chemically modified trypsin is a standard reagent in proteomics experiments but is usually not considered in database searches. Modification of trypsin is supposed to protect the protease against autolysis and the resulting loss of activity. Here, we show that modified trypsin is still subject to se...
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| Published in | Journal of proteome research Vol. 15; no. 4; pp. 1222 - 1229 |
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| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Chemical Society
01.04.2016
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1535-3893 1535-3907 1535-3907 |
| DOI | 10.1021/acs.jproteome.5b01105 |
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| Abstract | Chemically modified trypsin is a standard reagent in proteomics experiments but is usually not considered in database searches. Modification of trypsin is supposed to protect the protease against autolysis and the resulting loss of activity. Here, we show that modified trypsin is still subject to self-digestion, and, as a result, modified trypsin-derived peptides are present in standard digests. We depict that these peptides commonly lead to false-positive assignments even if native trypsin is considered in the database. Moreover, we present an easily implementable method to include modified trypsin in the database search with a minimal increase in search time and search space while efficiently avoiding these false-positive hits. |
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| AbstractList | Chemically modified trypsin is a standard reagent in proteomics experiments but is usually not considered in database searches. Modification of trypsin is supposed to protect the protease against autolysis and the resulting loss of activity. Here, we show that modified trypsin is still subject to self-digestion, and, as a result, modified trypsin-derived peptides are present in standard digests. We depict that these peptides commonly lead to false-positive assignments even if native trypsin is considered in the database. Moreover, we present an easily implementable method to include modified trypsin in the database search with a minimal increase in search time and search space while efficiently avoiding these false-positive hits. Chemically modified trypsin is a standard reagent in proteomics experiments but is usually not considered in database searches. Modification of trypsin is supposed to protect the protease against autolysis and the resulting loss of activity. Here, we show that modified trypsin is still subject to self-digestion, and, as a result, modified trypsin-derived peptides are present in standard digests. We depict that these peptides commonly lead to false-positive assignments even if native trypsin is considered in the database. Moreover, we present an easily implementable method to include modified trypsin in the database search with a minimal increase in search time and search space while efficiently avoiding these false-positive hits. Chemically modified trypsin is a standard reagent in proteomics experiments but is usually not considered in database searches. Modification of trypsin is supposed to protect the protease against autolysis and the resulting loss of activity. Here, we show that modified trypsin is still subject to self-digestion, and, as a result, modified trypsin-derived peptides are present in standard digests. We depict that these peptides commonly lead to false-positive assignments even if native trypsin is considered in the database. Moreover, we present an easily implementable method to include modified trypsin in the database search with a minimal increase in search time and search space while efficiently avoiding these false-positive hits.Chemically modified trypsin is a standard reagent in proteomics experiments but is usually not considered in database searches. Modification of trypsin is supposed to protect the protease against autolysis and the resulting loss of activity. Here, we show that modified trypsin is still subject to self-digestion, and, as a result, modified trypsin-derived peptides are present in standard digests. We depict that these peptides commonly lead to false-positive assignments even if native trypsin is considered in the database. Moreover, we present an easily implementable method to include modified trypsin in the database search with a minimal increase in search time and search space while efficiently avoiding these false-positive hits. |
| Author | Birner-Gruenberger, Ruth Liesinger, Laura Fritz, Katarina Schittmayer, Matthias Griss, Johannes |
| AuthorAffiliation | Department of Dermatology Research Unit Functional Proteomics and Metabolic Pathways Omics Center Graz, BioTechMed-Graz Institute of Pathology, Medical University of Graz Medical University of Vienna |
| AuthorAffiliation_xml | – name: Institute of Pathology, Medical University of Graz – name: Omics Center Graz, BioTechMed-Graz – name: Medical University of Vienna – name: Department of Dermatology – name: Research Unit Functional Proteomics and Metabolic Pathways |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26938934$$D View this record in MEDLINE/PubMed |
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| SubjectTerms | Amino Acid Sequence Animals autolysis Brain Chemistry Breast Neoplasms - chemistry Cell Line Chromatography, Liquid data analysis Data Interpretation, Statistical Databases, Protein Humans Membrane Proteins - analysis Membrane Proteins - chemistry Mice Neoplasm Proteins - analysis Neoplasm Proteins - chemistry Nerve Tissue Proteins - analysis Nerve Tissue Proteins - chemistry Peptide Fragments - analysis peptides Protein Structure, Secondary Proteolysis proteome proteomics Proteomics - methods Saccharomyces cerevisiae - chemistry Saccharomyces cerevisiae Proteins - analysis Saccharomyces cerevisiae Proteins - chemistry Tandem Mass Spectrometry trypsin Trypsin - chemistry |
| Title | Cleaning out the Litterbox of Proteomic Scientists’ Favorite Pet: Optimized Data Analysis Avoiding Trypsin Artifacts |
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