The emerging landscape of single-molecule protein sequencing technologies,Nature Methods

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The emerging landscape of single-molecule protein sequencing technologies
Nature Methods ( IF 48.0 ) Pub Date : 2021-06-07 , DOI: 10.1038/s41592-021-01143-1
Javier Antonio Alfaro ₁ , Peggy Bohländer ₂ , Mingjie Dai _{3,

4} , Mike Filius ₅ , Cecil J Howard ₆ , Xander F van Kooten ₇ , Shilo Ohayon ₇ , Adam Pomorski ₅ , Sonja Schmid ₈ , Aleksei Aksimentiev ₉ , Eric V Anslyn ₆ , Georges Bedran ₁ , Chan Cao ₁₀ , Mauro Chinappi ₁₁ , Etienne Coyaud ₁₂ , Cees Dekker ₅ , Gunnar Dittmar _{13,

14} , Nicholas Drachman ₁₅ , Rienk Eelkema ₂ , David Goodlett _{1,

16} , Sébastien Hentz ₁₇ , Umesh Kalathiya ₁ , Neil L Kelleher ₁₈ , Ryan T Kelly ₁₉ , Zvi Kelman _{20,

21} , Sung Hyun Kim ₅ , Bernhard Kuster _{22,

23} , David Rodriguez-Larrea ₂₄ , Stuart Lindsay ₂₅ , Giovanni Maglia ₂₆ , Edward M Marcotte ₂₇ , John P Marino ₂₀ , Christophe Masselon ₂₈ , Michael Mayer ₂₉ , Patroklos Samaras ₂₂ , Kumar Sarthak ₉ , Lusia Sepiashvili ₃₀ , Derek Stein ₁₅ , Meni Wanunu _{31,

32} , Mathias Wilhelm ₂₂ , Peng Yin _{3,

4} , Amit Meller _{7,

33} , Chirlmin Joo ₅

Affiliation

International Centre for Cancer Vaccine Science, University of Gdańsk, Gdańsk, Poland.
Faculty of Applied Sciences, Delft University of Technology, Delft, the Netherlands.
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
Department of BioNanoScience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, the Netherlands.
Department of Chemistry, University of Texas at Austin, Austin, TX, USA.
Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel.
NanoDynamicsLab, Laboratory of Biophysics, Wageningen University, Wageningen, the Netherlands.
Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Dipartimento di Ingegneria Industriale, Università di Roma Tor Vergata, Rome, Italy.
Univ. Lille, Inserm, CHU Lille, U1192-Protéomique Réponse Inflammatoire Spectrométrie de Masse-PRISM, Lille, France.
Department of Infection and Immunity, Luxembourg Institute of Health, Strassen, Luxembourg.
Department of Life Sciences and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
Department of Physics, Brown University, Providence, RI, USA.
Genome BC Proteomics Centre, University of Victoria, Victoria, British Columbia, Canada.
Université Grenoble Alpes, CEA, LETI, Grenoble, France.
Departments of Chemistry and Molecular Biosciences, and the Feinberg School of Medicine, Northwestern University, Evanston, IL, USA.
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA.
Institute for Bioscience and Biotechnology Research, National Institute of Standards and Technology, University of Maryland, Rockville, MD, USA.
Biomolecular Labeling Laboratory, Institute for Bioscience and Biotechnology Research, Rockville, MD, USA.
Chair of Proteomics and Bioanalytics, Technische Universität München, Freising, Germany.
Bavarian Center for Biomolecular Mass Spectrometry, Freising, Germany.
Department of Biochemistry and Molecular Biology, Biofisika Institute (CSIC, UPV/EHU), Leioa, Spain.
Biodesign Institute, School of Molecular Sciences, Department of Physics, Arizona State University, Tempe, AZ, USA.
Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, the Netherlands.
Department of Molecular Biosciences, Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, TX, USA.
Université Grenoble Alpes, CEA, Inserm, BGE U1038, Grenoble, France.
Adolphe Merkle Institute, University of Fribourg, Fribourg, Switzerland.
University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada.
Department of Physics, Northeastern University, Boston, MA, USA.
Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA.
Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa, Israel.

Single-cell profiling methods have had a profound impact on the understanding of cellular heterogeneity. While genomes and transcriptomes can be explored at the single-cell level, single-cell profiling of proteomes is not yet established. Here we describe new single-molecule protein sequencing and identification technologies alongside innovations in mass spectrometry that will eventually enable broad sequence coverage in single-cell profiling. These technologies will in turn facilitate biological discovery and open new avenues for ultrasensitive disease diagnostics.

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