Strategies for Development of a Next-Generation Protein Sequencing Platform.

Proteomic analysis can be a critical bottleneck in cellular characterization. The current paradigm relies primarily on mass spectrometry of peptides and affinity reagents (i.e., antibodies), both of which require a priori knowledge of the sample. An unbiased protein sequencing method, with a dynamic range that covers the full range of protein concentrations in proteomes, would revolutionize the field of proteomics, allowing a more facile characterization of novel gene products and subcellular complexes. To this end, several new platforms based on single-molecule protein-sequencing approaches have been proposed. This review summarizes four of these approaches, highlighting advantages, limitations, and challenges for each method towards advancing as a core technology for next-generation protein sequencing.

[1]  Ekaterina V. Poverennaya,et al.  The Size of the Human Proteome: The Width and Depth , 2016, International journal of analytical chemistry.

[2]  R. Aebersold,et al.  The quantitative and condition-dependent Escherichia coli proteome , 2015, Nature Biotechnology.

[3]  C. Dekker,et al.  Paving the way to single-molecule protein sequencing , 2018, Nature Nanotechnology.

[4]  B. Kuster,et al.  Mass-spectrometry-based draft of the human proteome , 2014, Nature.

[5]  I. Fournier,et al.  Parafilm-assisted microdissection: a sampling method for mass spectrometry-based identification of differentially expressed prostate cancer protein biomarkers. , 2015, Chemical communications.

[6]  S. Lindsay,et al.  Physical model for recognition tunneling , 2015, Nanotechnology.

[7]  L. Hood,et al.  Protein sequence analysis: automated microsequencing. , 1983, Science.

[8]  Benjamin Borgo,et al.  Computer-aided design of a catalyst for Edman degradation utilizing substrate-assisted catalysis , 2014, Protein Science : A Publication of the Protein Society.

[9]  C. Dekker.  Solid-state nanopores. , 2007, Nature nanotechnology.

[10]  H. Bayley,et al.  Single-molecule site-specific detection of protein phosphorylation with a nanopore , 2014, Nature Biotechnology.

[11]  Yao Yao,et al.  Single-molecule protein sequencing through fingerprinting: computational assessment , 2015, Physical Biology.

[12]  Single-molecule peptide fingerprinting , 2018, Proceedings of the National Academy of Sciences.

[13]  M. Mann,et al.  The abc's (and xyz's) of peptide sequencing , 2004, Nature Reviews Molecular Cell Biology.

[14]  M. Furuhashi,et al.  Detection of post-translational modifications in single peptides using electron tunnelling currents. , 2014, Nature nanotechnology.

[15]  G. Omenn.  The strategy, organization, and progress of the HUPO Human Proteome Project. , 2014, Journal of proteomics.

[16]  I. Fournier,et al.  Spatially‐resolved protein surface microsampling from tissue sections using liquid extraction surface analysis , 2016, Proteomics.

[17]  G. Salvesen,et al.  Caspases: Intracellular Signaling by Proteolysis , 1997, Cell.

[18]  Edward M. Marcotte,et al.  A Theoretical Justification for Single Molecule Peptide Sequencing , 2014, bioRxiv.

[19]  Yasuteru Urano,et al.  Asymmetric Rhodamine-Based Fluorescent Probe for Multicolour In Vivo Imaging. , 2016, Chemistry.

[20]  Bernhard Palsson,et al.  In silico biology through “omics” , 2002, Nature Biotechnology.

[21]  Adam H. Marblestone,et al.  A theoretical analysis of single molecule protein sequencing via weak binding spectra , 2018, bioRxiv.

[22]  H. Paulus,et al.  Protein splicing and related forms of protein autoprocessing. , 2000, Annual review of biochemistry.

[23]  Thilo Muth,et al.  A Potential Golden Age to Come—Current Tools, Recent Use Cases, and Future Avenues for De Novo Sequencing in Proteomics , 2018, Proteomics.

[24]  Gregory Timp,et al.  Discriminating Residue Substitutions in a Single Protein Molecule Using a Sub-nanopore. , 2017, ACS nano.

[25]  M. Maurizi,et al.  Processive degradation of proteins by the ATP-dependent Clp protease from Escherichia coli. Requirement for the multiple array of active sites in ClpP but not ATP hydrolysis. , 1994, The Journal of biological chemistry.

[26]  S. Cockroft,et al.  Biological Nanopores for Single‐Molecule Biophysics , 2009, Chembiochem : a European journal of chemical biology.

[27]  Cees Dekker,et al.  Fast translocation of proteins through solid state nanopores. , 2013, Nano letters.

[28]  S. Quake,et al.  The promise and challenge of high-throughput sequencing of the antibody repertoire , 2014, Nature Biotechnology.

[29]  A. Herr,et al.  Detection of Isoforms Differing by a Single Charge Unit in Individual Cells. , 2016, Angewandte Chemie.

[30]  Jin He,et al.  Identifying single bases in a DNA oligomer with electron tunnelling. , 2010, Nature nanotechnology.

[31]  Francesca Giordano,et al.  Oxford Nanopore MinION Sequencing and Genome Assembly , 2016, Genom. Proteom. Bioinform..

[33]  Mark W Grinstaff,et al.  Single-molecule protein sensing in a nanopore: a tutorial. , 2018, Chemical Society reviews.

[34]  H. D. Vanguilder,et al.  Twenty-five years of quantitative PCR for gene expression analysis. , 2008, BioTechniques.

[35]  J. Betton,et al.  Sensing proteins through nanopores: fundamental to applications. , 2012, ACS chemical biology.

[36]  K. Resing,et al.  Mapping protein post-translational modifications with mass spectrometry , 2007, Nature Methods.

[37]  Lior Pachter,et al.  Near-optimal probabilistic RNA-seq quantification , 2016, Nature Biotechnology.

[38]  Anastasia Baryshnikova,et al.  Unification of Protein Abundance Datasets Yields a Quantitative Saccharomyces cerevisiae Proteome. , 2018, Cell systems.

[39]  J. Strickler,et al.  Application of high-performance liquid chromatographic peptide purification to protein microsequencing by solid-phase Edman degradation. , 1982, Analytical biochemistry.

[40]  Amy E. Herr,et al.  Single-cell western blotting , 2014, Nature Methods.

[41]  H. Bayley,et al.  Multistep protein unfolding during nanopore translocation. , 2013, Nature nanotechnology.

[42]  R. Sauer,et al.  The SsrA–SmpB system for protein tagging, directed degradation and ribosome rescue , 2000, Nature Structural Biology.

[43]  K. Medzihradszky,et al.  Lessons in de novo peptide sequencing by tandem mass spectrometry. , 2015, Mass spectrometry reviews.

[44]  Jürgen Cox,et al.  Computational Methods for Understanding Mass Spectrometry–Based Shotgun Proteomics Data , 2018, Annual Review of Biomedical Data Science.

[45]  M. Taniguchi,et al.  Fast and low-noise tunnelling current measurements for single-molecule detection in an electrolyte solution using insulator-protected nanoelectrodes. , 2017, Nanoscale.

[46]  E. Mardis.  DNA sequencing technologies: 2006–2016 , 2017, Nature Protocols.

[47]  Libo Li,et al.  Protein Translocation through a MoS2 Nanopore:A Molecular Dynamics Study , 2018 .

[48]  Adrian O. Olivares,et al.  Single-Molecule Protein Unfolding and Translocation by an ATP-Fueled Proteolytic Machine , 2011, Cell.

[49]  Yifan Liu,et al.  Advancing single-cell proteomics and metabolomics with microfluidic technologies. , 2019, The Analyst.

[50]  Peiming Zhang,et al.  Synthesis, physicochemical properties, and hydrogen bonding of 4(5)-substituted 1-H-imidazole-2-carboxamide, a potential universal reader for DNA sequencing by recognition tunneling. , 2012, Chemistry.

[51]  Iulia M Lazar,et al.  Microfluidic liquid chromatography system for proteomic applications and biomarker screening. , 2006, Analytical chemistry.

[52]  Manuel A. S. Santos,et al.  Protein mistranslation: friend or foe? , 2014, Trends in biochemical sciences.

[53]  Weiwen Zhang,et al.  Integrating multiple 'omics' analysis for microbial biology: application and methodologies. , 2010, Microbiology.

[54]  S. Lindsay,et al.  Single Molecule Spectroscopy of Amino Acids and Peptides by Recognition Tunneling , 2014, Nature nanotechnology.

[55]  M. Taniguchi,et al.  Single-molecule sensing electrode embedded in-plane nanopore , 2011, Scientific reports.

[56]  P. Hanson,et al.  AAA+ proteins: have engine, will work , 2005, Nature Reviews Molecular Cell Biology.

[57]  R. Caprioli,et al.  Enhanced Spatially Resolved Proteomics Using On-Tissue Hydrogel-Mediated Protein Digestion. , 2017, Analytical chemistry.

[58]  Z. Kelman,et al.  Engineering ClpS for selective and enhanced N-terminal amino acid binding , 2019, Applied Microbiology and Biotechnology.

[59]  S. Gottesman,et al.  Sequence and structure of Clp P, the proteolytic component of the ATP-dependent Clp protease of Escherichia coli. , 1990, The Journal of biological chemistry.

[60]  Yoonkyung Park,et al.  Single-Molecule Dynamics and Discrimination between Hydrophilic and Hydrophobic Amino Acids in Peptides, through Controllable, Stepwise Translocation across Nanopores , 2018, Polymers.

[61]  Fabio Cecconi,et al.  Protein sequencing via nanopore based devices: a nanofluidics perspective , 2018, Journal of physics. Condensed matter : an Institute of Physics journal.

[62]  Kazuki Saito,et al.  Integrated omics approaches in plant systems biology. , 2009, Current opinion in chemical biology.

[63]  C. Dekker,et al.  SDS-assisted protein transport through solid-state nanopores. , 2017, Nanoscale.

[64]  D. Black.  Mechanisms of alternative pre-messenger RNA splicing. , 2003, Annual review of biochemistry.

[65]  F. Richards.  The interpretation of protein structures: total volume, group volume distributions and packing density. , 1974, Journal of molecular biology.

[66]  Electronic single-molecule identification of carbohydrate isomers by recognition tunnelling , 2016, Nature communications.

[67]  A. D’Alessandro,et al.  Meat science: From proteomics to integrated omics towards system biology. , 2013, Journal of proteomics.

[68]  Yoonkyung Park,et al.  Protein Nanopore-Based Discrimination between Selected Neutral Amino Acids from Polypeptides. , 2017, Langmuir : the ACS journal of surfaces and colloids.

[69]  S. Lindsay,et al.  Click Addition of a DNA Thread to the N-Termini of Peptides for Their Translocation through Solid-State Nanopores. , 2015, ACS nano.

[70]  E. Marcotte,et al.  Solution-phase and solid-phase sequential, selective modification of side chains in KDYWEC and KDYWE as models for usage in single-molecule protein sequencing. , 2017, New journal of chemistry = Nouveau journal de chimie.

[71]  Mark Akeson,et al.  Unfoldase-mediated protein translocation through an α-hemolysin nanopore , 2013, Nature Biotechnology.

[72]  E. Wolf.  Principles of Electron Tunneling Spectroscopy: Second Edition , 2012 .

[73]  J. Pelta,et al.  Identification of single amino acid differences in uniformly charged homopolymeric peptides with aerolysin nanopore , 2018, Nature Communications.

[74]  J. Jia,et al.  Scanning Tunneling Microscopy , 2013 .

[75]  O. Schilling,et al.  Protein amino-terminal modifications and proteomic approaches for N-terminal profiling. , 2015, Current opinion in chemical biology.

[76]  Rosa Viner,et al.  High resolution top-down experimental strategies on the Orbitrap platform. , 2017, Journal of proteomics.

[77]  B. Tian,et al.  RNA‐Seq methods for transcriptome analysis , 2017, Wiley interdisciplinary reviews. RNA.

[78]  Ki-Bum Kim,et al.  Differentiation of selectively labeled peptides using solid-state nanopores. , 2019, Nanoscale.

[79]  W. Koh,et al.  Single-cell genome sequencing: current state of the science , 2016, Nature Reviews Genetics.

[80]  Pavel A. Pevzner,et al.  Single-molecule protein identification by sub-nanopore sensors , 2016, PLoS Comput. Biol..

[81]  A. deMello,et al.  The past, present and potential for microfluidic reactor technology in chemical synthesis. , 2013, Nature chemistry.

[82]  V. Ananikov,et al.  How sensitive and accurate are routine NMR and MS measurements , 2015 .

[83]  S. Gallagher.  One‐Dimensional SDS Gel Electrophoresis of Proteins , 2012, Current protocols in molecular biology.

[84]  Gregory Timp,et al.  Reading the primary structure of a protein with 0.07 nm3 resolution using a subnanometre-diameter pore. , 2016, Nature nanotechnology.

[85]  Bruno Domon,et al.  Advances in high‐resolution accurate mass spectrometry application to targeted proteomics , 2015, Proteomics.

[86]  Edward M Marcotte,et al.  Highly parallel single-molecule identification of proteins in zeptomole-scale mixtures , 2018, Nature Biotechnology.