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Spritz : A Proteogenomic Database Engine
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- Cesnik, Anthony J. (author)
- KTH,Science for Life Laboratory, SciLifeLab,Univ Wisconsin Madison, Dept Chem, Madison, WI 53706 USA.;KTH Royal Inst Technol, Sci Life Lab, Sch Engn Sci Chem Biotechnol & Hlth, S-17121 Stockholm, Sweden.;Stanford Univ, Dept Genet, Stanford, CA 94305 USA.;Chan Zuckerberg Biohub, San Francisco, CA 94158 USA.
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- Miller, Rachel M. (author)
- Univ Wisconsin Madison, Dept Chem, Madison, WI 53706 USA.
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- Ibrahim, Khairina (author)
- Univ Wisconsin Madison, Dept Chem, Madison, WI 53706 USA.
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- (creator_code:org_t)
- 2020-09-23
- 2021
- English.
- In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 20:4, s. 1826-1834
- Journal article (peer-reviewed)
Abstract
Subject headings
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- Proteoforms are the workhorses of the cell, and subtle differences between their amino acid sequences or post-translational modifications (PTMs) can change their biological function. To most effectively identify and quantify proteoforms in genetically diverse samples by mass spectrometry (MS), it is advantageous to search the MS data against a sample-specific protein database that is tailored to the sample being analyzed, in that it contains the correct amino acid sequences and relevant PTMs for that sample. To this end, we have developed Spritz (https://smith-chem-wisc.github.io/Spritz/), an open-source software tool for generating protein databases annotated with sequence variations and PTMs. We provide a simple graphical user interface for Windows and scripts that can be run on any operating system. Spritz automatically sets up and executes approximately 20 tools, which enable the construction of a proteogenomic database from only raw RNA sequencing data. Sequence variations that are discovered in RNA sequencing data upon comparison to the Ensembl reference genome are annotated on proteins in these databases, and PTM annotations are transferred from UniProt. Modifications can also be discovered and added to the database using bottom-up mass spectrometry data and global PTM discovery in MetaMorpheus. We demonstrate that such sample-specific databases allow the identification of variant peptides, modified variant peptides, and variant proteoforms by searching bottom-up and top-down proteomic data from the Jurkat human T lymphocyte cell line and demonstrate the identification of phosphorylated variant sites with phosphoproteomic data from the U2OS human osteosarcoma cell line.
Subject headings
- NATURVETENSKAP -- Biologi -- Bioinformatik och systembiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)
Keyword
- RNA-Seq
- proteogenomics
- sequence variations
- modifications
- proteoform
- top-down
- sample-specific
- transcriptomics
- PTMs
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- ref (subject category)
- art (subject category)
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