A Mass Spectrometric-Derived Cell Surface Protein Atlas

Damaris Bausch‑Fluck, Andreas Hofmann, Thomas Bock, Andreas P. Frei, Ferdinando Cerciello, Andrea Jacobs, Hansjoerg Moest, Ulrich Omasits, Rebekah L. Gundry, Charles Yoon, Ralph Schiess, Alexander Schmidt, Paulina Mirkowska, Anetta Härtlová, Jennifer E. Van Eyk, Jean Pierre Bourquin, Ruedi Aebersold, Kenneth R. Boheler, Peter Zandstra, Bernd Wollscheid

Abstract

Cell surface proteins are major targets of biomedical research due to their utility as cellular markers and their extracellular accessibility for pharmacological intervention. However, information about the cell surface protein repertoire (the surfaceome) of individual cells is only sparsely available. Here, we applied the Cell Surface Capture (CSC) technology to 41 human and 31 mouse cell types to generate a mass-spectrometry derived Cell Surface Protein Atlas (CSPA) providing cellular surfaceome snapshots at high resolution. The CSPA is presented in form of an easy-to-navigate interactive database, a downloadable data matrix and with tools for targeted surfaceome rediscovery (http://wlab.ethz.ch/cspa). The cellular surfaceome snapshots of different cell types, including cancer cells, resulted in a combined dataset of 1492 human and 1296 mouse cell surface glycoproteins, providing experimental evidence for their cell surface expression on different celltypes, including 136 G-protein coupled receptors and 75 membrane receptor tyrosine-protein kinases. Integrated analysis of the CSPA reveals that the concerted biological function of individual cell types is mainly guided by quantitative rather than qualitative surfaceome differences. The CSPA will be useful for the evaluation of drug targets, for the improved classification of cell types and for a better understanding of the surfaceome and its concerted biological functions in complex signaling microenvironments.

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Highlights

  • 41 human cell types
  • 31 mouse cell types
  • 1492 human cell surface glycoproteins
  • 1296 mouse cell surface glycoproteins
  • 13942 mouse and human derived N-glycopeptides

News

2018-11-01 new
The in silico human surfaceome website is online now! Explore a new public biomedical resource complementing the Cell Surface Protein Atlas (CSPA) and use it to uncover cellular phenotypes and new surfaceome markers.
#Surfaceome #HumanProteome #CellAtlas
2018-10-31 new
We just published a manuscript on "The in silico human surfaceome" employing a machine learning approach (SURFY). This new public biomedical resource can be used to uncover cellular phenotypes and new surfaceome markers!
#Surfaceome #HumanProteome #CellAtlas #PNAS
2018-10-10 new
Our review/perspective on "Surfaceome Nanoscale Organization and Extracellular Interaction Networks" in "Current Opinion in Chemical Biology" is now online! Here's a share link for free access for 50 days: review
Thanks to editors Ileana Cristea & @lilley_ks!

Visualization tools

Protter
An open-source tool specially helpful for visualization of cell surface proteins. It includes proteoforms and interactive integration of annotated and predicted sequence features together with experimental proteomic evidence!
In silico human surfaceome new
An interactive tool for exploring the complete list of predicted surfaceome proteins. Allows to visualize and compare surfaceome landscape grouped into their functional classes.

Downloads

Annotation of cell types

Description and origin of all cell types and tissues used for the CSPA.

Matrix of all proteins and their detection in the different cell types.

Excel file containing 6 tables organized in different sheets:

  1. List of all proteins identified within the different cell types
  2. Matrix of 1492 human proteins against 47 human cell types
  3. Matrix of 1296 mouse proteins against 31 mouse cell types
  4. Table containing the number of identified proteins of each cell type
  5. Matrix with human surfaceome proteins and cells and their estimated relative quantities in log2 scale
  6. Matrix with mouse surfaceome proteins and cells and their estimated relative quantities in log2 scale

Sisyphus CSPA

Filemaker based database containing the easy-to-navigate Sisyphus database executable.

CSPA validated surfaceome proteins

Excel file containing all human and mouse surfaceome proteins in two tables and an additional table with all identified N-glycopeptides:

  1. List of 1492 human surfaceome proteins and their annotation.
  2. List of 1296 mouse surfaceome proteins and their annotation.
  3. List of 13942 mouse and human derived N-glycopeptides, including identified modified form.

Corrected topologies

PDF files with original and based on N-glycopeptide identification corrected topology pictures of 51 human proteins and 39 mouse proteins. The pictures were created with PROTTER and identified N-glycopeptides were marked yellow.

CSPA based spectral libraries for human proteins

ZIP file, containing a README.txt file and two subfolders with the respective spectral libraries:

  1. The .pepidx, .spidx and .splib file of the human spectral library for proteins within the CSPA. The sequence motiv N-X-S/T has been modified to D-X-S/T, which corresponds to a deamidated asparagine (N). Methionines are variable modified by oxidation and a decoy spectral library is appended.
  2. The .pepidx, .spidx and .splib file of the human spectral library for proteins within the CSPA. Asparagines and methionines can be searched with variable modifications of deamiation and oxidation, respectively and a decoy spectral library is appended.

CSPA based spectral libraries for mouse proteins

ZIP file, containing a README.txt file and two subfolders with the respective spectral libraries:

  1. The .pepidx, .spidx and .splib file of the mouse spectral library for proteins within the CSPA. The sequence motiv N-X-S/T has been modified to D-X-S/T, which corresponds to a deamidated asparagine (N). Methionines are variable modified by oxidation and a decoy spectral library is appended.
  2. The .pepidx, .spidx and .splib file of the mouse spectral library for proteins within the CSPA. Asparagines and methionines can be searched with variable modifications of deamiation and oxidation, respectively and a decoy spectral library is appended.

CSPA toolbox

Excel file containing tables for generating inclusion lists and transition list of surfaceome proteins within the CSPA:

  1. Human inclusion list
  2. Mouse inclusion list
  3. Transition list
  4. Measured transitions of Figure 6

Cite

If you use the Cell Surface Protein Atlas for your research please cite:

Bausch-Fluck D, Hofmann A, Bock T, Frei AP, Cerciello F, et al. (2015)
A Mass Spectrometric-Derived Cell Surface Protein Atlas.
PLoS One 10: e0121314.

Contact

Corresponding Author
Prof. Dr. Bernd Wollscheid wbernd@ethz.ch
ETH Zurich
Institute of Molecular Systems Biology
Auguste-Piccard-Hof 1
8093 Zürich, Switzerland
http://www.imsb.ethz.ch/research/wollscheid.html