Journal Article

An open-source computational and data resource to analyze digital maps of immunopeptidomes

Sturm, Theo, Schuster, Heiko, Campbell, David S, Sette, Alessandro, Marcilla, Miguel, Chiek Koh, Ching, Ternette, Nicola, Rammensee, Hans-Georg, Caron, Etienne, Lindestam Arlehamn, Cecilia S, Purcell, Anthony W, Ramarathinam, Sri H, Deutsch, Eric W, Moritz, Robert L, Stevanovic, Stefan, Schittenhelm, Ralf B, Lam, Henry, Kowalewski, Daniel J, Alpízar, Adán, Aebersold, Ruedi, Espona, Lucia, Navarro, Pedro, Rabsteyn, Armin, Gillet, Ludovic C, Kim, Sangtae

2015

Overview

We present a novel mass spectrometry-based high-throughput workflow and an open-source computational and data resource to reproducibly identify and quantify HLA-associated peptides. Collectively, the resources support the generation of HLA allele-specific peptide assay libraries consisting of consensus fragment ion spectra, and the analysis of quantitative digital maps of HLA peptidomes generated from a range of biological sources by SWATH mass spectrometry (MS). This study represents the first community-based effort to develop a robust platform for the reproducible and quantitative measurement of the entire repertoire of peptides presented by HLA molecules, an essential step towards the design of efficient immunotherapies. The cells of the immune system protect us by recognizing telltale molecules produced by damaged and diseased cells, or by infection-causing microorganisms (which are also called pathogens). To help with this process, the cells in our bodies display small fragments of proteins (called peptides) on their surface that are then checked by the immune cells. Collectively, these peptides are referred to as the ‘immunopeptidome’, and deciphering the complexity of the human immunopeptidome is important for both basic research and medical science. Such an achievement would help to guide the development of next-generation vaccines and therapies against autoimmune disorders, infectious diseases and cancers. In the past, immune peptides were mostly identified using a technique that is commonly called ‘shotgun’ mass spectrometry. However, this approach doesn't always provide reproducible results. In 2012, researchers reported the development of a new approach—which they called ‘SWATH’ mass spectrometry—that could yield more reproducible data. Now, Caron et al.—including many of the researchers involved in the 2012 study—have developed a large collection of standardized tests that use SWATH mass spectrometry to analyze the human immunopeptidome. The workflow and the computational and data resources developed as part of this international effort are the first steps toward highly reproducible and measurable analyses of the immunopeptidome across many samples. Moreover, the large repository of assays generated by the project has been made public and will serve a large community of researchers, which should enable better collaborations. In the future, SWATH mass spectrometry could be used as a robust technology for the reproducible detection and measurement of pathogen-specific or cancer-specific immune peptides. This could greatly help in the design of personalized immune-based therapies.

• Publisher: eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Amino acids / Antigen Presentation / Antigens / Antigens - chemistry / Antigens - immunology / BASIC BIOLOGICAL SCIENCES / Biology / Cancer / Computational and Systems Biology / Computational Biology - methods / Computer applications / Data analysis / Data processing / Databases, Factual / DIA / High-Throughput Screening Assays - methods / Histocompatibility antigen HLA / HLA Antigens - metabolism / human leukocytes antigen / Immunology / immunopeptidome / Immunotherapy / Laboratories / Lymphocytes / Mass spectrometry / Mass Spectrometry - methods / Mass spectroscopy / Peptides / Peptides - chemistry / Peptides - immunology / Scientific imaging / SWATH-MS / targeted mass spectrometry / Tools and Resources