Granted Patent
B2
US 12,196,760 · App. 17/146,165 · Granted Jan 14, 2025
Molecular neighborhood detection by oligonucleotides
Inventors:
Edward Marcotte (Austin, TX); Jagannath Swaminathan (Austin, TX); Andrew Ellington (Austin, TX); Alexander Boulgakov (Austin, TX); Jon Laurent (Austin, TX); Raghav Shroff (Austin, TX); Erhu Xiong (Austin, TX); Sanchita Bhadra (Austin, TX); Brendan Floyd (Austin, TX); Eric Anslyn (Austin, TX)
View Patent ↗
Loading inventors, assignments & file history…
Abstract
The present disclosure provides methods for molecular neighborhood detection of molecules, such as by iterative proximity ligation or split-and-pool methods for obtaining positional information.
Claims (28)
1. A method for uniquely labeling one or more peptides comprising:
(a) obtaining a sample comprising a plurality of peptides free in solution;
(b) attaching oligonucleotide tags comprising unique amino acid-specific barcodes to the plurality of peptides, thereby generating a first plurality of tagged-peptides free in solution;
(c) splitting the first plurality of tagged-peptides into three or more compartments;
(d) labeling the first plurality of tagged-peptides with a first compartment-specific oligonucleotide tag, thereby generating a second plurality of tagged-peptides free in solution;
(e) pooling the second plurality of tagged-peptides from the three or more compartments, and splitting the second plurality of tagged-peptides into three or more compartments; and
(f) attaching a second compartment-specific oligonucleotide tag to the second plurality of tagged-peptides, thereby obtaining a plurality of uniquely labeled peptides free in solution.
2. The method of claim 1 , further comprising another one or more rounds of pooling the uniquely labeled peptides, splitting the uniquely labeled peptides, and attaching additional compartment-specific oligonucleotide tags to obtain further uniquely labeled peptides.
3. The method of claim 1 , wherein the unique amino acid-specific barcodes are specific for lysine, cysteine, glutamic acid, aspartic acid, tyrosine, tryptophan, or histidine.
4. The method of claim 1 , wherein amino acids in the plurality of peptides free in solution comprise post-translationally modified side chains.
5. The method of claim 4 , wherein the post-translationally modified side chains comprise phosphorylation, glycosylation, methylation, citrullination, or any combination thereof.
6. The method of claim 1 , wherein the unique amino acid-specific barcodes comprise a functional group to attach the unique amino acid-specific barcodes to amino acids in the plurality of peptides free in solution.
7. The method of claim 6 , wherein the functional group is selected from the group consisting of a succinimidyl ester, an iodoacetamide, a maleimide, amines, a 4-phenyl-3H-1,2,4-triazole-3,5 (4H)-dione (PTAD), a 2,4-dinitrobenzenesulfenyl chloride, and a thiol.
8. The method of claim 1 , further comprising generating the plurality of peptides free in solution by digesting a protein with an enzyme.
9. The method of claim 8 , wherein the digesting is site-specific.
10. The method of claim 8 , wherein the enzyme is trypsin.
11. The method of claim 8 , wherein the digesting the protein does not remove an N-terminal amino acid.
12. The method of claim 1 , wherein the oligonucleotide tags comprising the unique amino acid-specific barcodes, the first compartment-specific oligonucleotide tags, and/or the second compartment-specific oligonucleotide tags are single-stranded.
13. The method of claim 1 , wherein the first compartment-specific oligonucleotide tag or the second compartment-specific oligonucleotide tag is single-stranded.
14. The method of claim 1 , wherein the labeling or the attaching comprises enzymatic ligation.
15. The method of claim 14 , wherein the enzymatic ligation comprises blunt-end ligation.
16. The method of claim 1 , further comprising:
(a) performing next-generation sequencing on the oligonucleotide tags comprising the unique amino acid-specific barcodes, the first compartment specific oligonucleotide tag, and the second compartment-specific oligonucleotide tag; and
(b) obtaining an amino acid pattern for a single peptide from the next-generation sequencing and comparing the amino acid pattern to a proteome of an organism to identify the uniquely labeled peptide.
17. The method of claim 1 , wherein the labeling or the attaching comprises chemical ligation.
18. The method of claim 1 , wherein the uniquely labeled peptide comprises a unique ligated barcode.
19. The method of claim 1 , further comprising counting a number of amino acids of an amino acid type of the uniquely labeled peptide.
20. The method of claim 1 , wherein the first plurality of tagged-peptides free in solution of (c) or the second plurality of tagged-peptides free in solution in (e) is split into 96 or more compartments.
Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Sep 9, 2024
From: MARCOTTE, EDWARD; SWAMINATHAN, JAGANNATH; ELLINGTON, ANDREW; BOULGAKOV, ALEXANDER; LAURENT, JON; SHROFF, RAGHAV; XIONG, ERHU; BHADRA, SANCHITA; FLOYD, BRENDAN; ANSLYN, ERIC
To: BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM
Reel/Frame 068524/0912 →
CONFIRMATORY LICENSE
Recorded Dec 26, 2023
From: UNIVERSITY OF TEXAS AT AUSTIN
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 066128/0432 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 21, 2022
From: MARCOTTE, EDWARD; SWAMINATHAN, JAGANNATH; BOULGAKOV, ALEXANDER; SHROFF, RAGHAV; BHADRA, SANCHITA; ANSLYN, ERIC; ELLINGTON, ANDREW; LAURENT, JON; XIONG, ERHU; FLOYD, BRENDAN
To: BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM
Reel/Frame 059056/0705 →
Continuity (3)
Continuation
PCTUS2019041562
· Jul 12, 2019
Provisional Application
62697179
· Jul 12, 2018
References Cited (400)
US 5591646A
· Hudson et al.
· 1997
[cited by applicant]
US 5605809A
· Komoriya et al.
· 1997
[cited by applicant]
US 5902723A
· Dower et al.
· 1999
[cited by applicant]
US 5914313A
· Bouffard et al.
· 1999
[cited by applicant]
US 6156527A
· Schmidt et al.
· 2000
[cited by applicant]
US 6326136B1
· Lazar et al.
· 2001
[cited by applicant]
US 6902936B2
· Qui et al.
· 2005
[cited by applicant]
US 7329505B2
· Marmé
· 2008
[cited by applicant]
US 7351540B1
· Carr
· 2008
[cited by applicant]
US 7468258B2
· Owen
· 2008
[cited by applicant]
US 7641862B2
· Noetzel et al.
· 2010
[cited by applicant]
US 8268977B2
· Kool et al.
· 2012
[cited by applicant]
US 8569481B2
· Koster et al.
· 2013
[cited by applicant]
US 8609423B2
· Diller et al.
· 2013
[cited by applicant]
US 8778685B2
· Diller et al.
· 2014
[cited by applicant]
US 9011772B2
· Norderhaug et al.
· 2015
[cited by applicant]
US 9175035B2
· Konno et al.
· 2015
[cited by applicant]
US 9188586B2
· Fan et al.
· 2015
[cited by applicant]
US 9435810B2
· Havranek et al.
· 2016
[cited by applicant]
US 9470680B2
· Gonzalez et al.
· 2016
[cited by applicant]
US 9566335B1
· Emili et al.
· 2017
[cited by applicant]
US 9580736B2
· Tan et al.
· 2017
[cited by applicant]
US 9625469B2
· Marcotte et al.
· 2017
[cited by applicant]
US 9689868B2
· Kelts et al.
· 2017
[cited by applicant]
US 9983211B2
· Diller et al.
· 2018
[cited by applicant]
US 20020137045A1
· Lukhtanov et al.
· 2002
[cited by applicant]
US 20020168682A1
· Goodlett et al.
· 2002
[cited by applicant]
US 20020182117A1
· Coassin et al.
· 2002
[cited by applicant]
US 20040029181A1
· Ueyama et al.
· 2004
[cited by applicant]
US 20040053356A1
· Duewel et al.
· 2004
[cited by applicant]
US 20040059522A1
· Han et al.
· 2004
[cited by applicant]
US 20040086521A1
· Kropshofer et al.
· 2004
[cited by applicant]
US 20050003558A1
· Zuckermann et al.
· 2005
[cited by applicant]
US 20050020810A1
· Ternansky et al.
· 2005
[cited by applicant]
US 20080044405A1
· Dedecker et al.
· 2008
[cited by applicant]
US 20080090238A1
· Yang et al.
· 2008
[cited by applicant]
US 20080206141A1
· Johannesen et al.
· 2008
[cited by applicant]
US 20080242838A1
· Peters et al.
· 2008
[cited by applicant]
US 20100047170A1
· Denmeade et al.
· 2010
[cited by applicant]
US 20100047814A1
· Bruce et al.
· 2010
[cited by applicant]
US 20100233095A1
· Duan et al.
· 2010
[cited by applicant]
US 20100255518A1
· Goix et al.
· 2010
[cited by applicant]
US 20100331199A1
· Stoll et al.
· 2010
[cited by applicant]
US 20110027300A1
· Kamil et al.
· 2011
[cited by applicant]
US 20140024124A1
· Shinohara et al.
· 2014
[cited by applicant]
US 20150087526A1
· Hesselberth
· 2015
[cited by applicant]
US 20150185199A1
· Joo et al.
· 2015
[cited by applicant]
US 20160194699A1
· Borodina et al.
· 2016
[cited by applicant]
US 20170212126A1
· Emili et al.
· 2017
[cited by applicant]
US 20170343545A1
· Hadrup et al.
· 2017
[cited by applicant]
US 20180284125A1
· Gordon et al.
· 2018
[cited by applicant]
US 20190085412A1
· Fan et al.
· 2019
[cited by applicant]
US 20200123593A1
· Rothberg et al.
· 2020
[cited by applicant]
US 20200123594A1
· Rothberg et al.
· 2020
[cited by applicant]
US 20200124613A1
· Marcotte et al.
· 2020
[cited by applicant]
US 20200348307A1
· Beierle et al.
· 2020
[cited by applicant]
US 20210010070A1
· Schnall-Levin et al.
· 2021
[cited by applicant]
US 20210215706A1
· Marcotte et al.
· 2021
[cited by applicant]
US 20210215707A1
· Marcotte et al.
· 2021
[cited by applicant]
US 20220163536A1
· Marcotte et al.
· 2022
[cited by applicant]
EP 1163519
· 2001
[cited by applicant]
EP 2518514
· 2012
[cited by applicant]
EP 3219712
· 2017
[cited by applicant]
EP 3821010
· 2021
[cited by applicant]
GB 2610078
· 2023
[cited by applicant]
WO WO9100296
· 1991
[cited by applicant]
WO WO1993012230
· 1993
[cited by applicant]
WO WO2007070021
· 2007
[cited by applicant]
WO WO2007104219
· 2007
[cited by applicant]
WO WO2007120805
· 2007
[cited by applicant]
WO WO2008109176
· 2008
[cited by applicant]
WO WO2009090651
· 2009
[cited by applicant]
WO WO2009158006
· 2009
[cited by applicant]
WO WO201005322
· 2010
[cited by applicant]
WO WO2010044892
· 2010
[cited by applicant]
WO WO2010065322
· 2010
[cited by applicant]
WO WO2010065531
· 2010
[cited by applicant]
WO WO2012019765
· 2012
[cited by applicant]
WO WO2012083261
· 2012
[cited by applicant]
WO WO2012178023
· 2012
[cited by applicant]
WO WO2013112745
· 2013
[cited by applicant]
WO WO2014031997
· 2014
[cited by applicant]
WO WO2014106957
· 2014
[cited by applicant]
WO WO2014124338
· 2014
[cited by applicant]
WO WO2014210353
· 2014
[cited by applicant]
WO WO201500893
· 2015
[cited by applicant]
WO WO2015035108
· 2015
[cited by applicant]
WO WO2015153381A2
· 2015
[cited by applicant]
WO WO2015200893
· 2015
[cited by applicant]
WO WO2016069124
· 2016
[cited by applicant]
WO WO2016114970
· 2016
[cited by applicant]
WO WO2016145416
· 2016
[cited by applicant]
WO WO2016164530
· 2016
[cited by applicant]
WO WO2017063093
· 2017
[cited by applicant]
WO WO2017075265
· 2017
[cited by applicant]
WO WO2017079573
· 2017
[cited by applicant]
WO WO2017079593
· 2017
[cited by applicant]
WO WO2017192633
· 2017
[cited by applicant]
WO WO2017219027
· 2017
[cited by applicant]
WO WO2018005559
· 2018
[cited by applicant]
WO WO2018075693
· 2018
[cited by applicant]
WO WO2018119447
· 2018
[cited by applicant]
WO WO2018140966
· 2018
[cited by applicant]
WO WO2019063827
· 2019
[cited by applicant]
WO WO2019089836
· 2019
[cited by applicant]
WO WO2019089846
· 2019
[cited by applicant]
WO WO2019089851
· 2019
[cited by applicant]
WO WO2019125982
· 2019
[cited by applicant]
WO WO2019178033
· 2019
[cited by applicant]
WO WO2020014586
· 2020
[cited by applicant]
WO WO2020023488
· 2020
[cited by applicant]
WO WO2020037046
· 2020
[cited by applicant]
WO WO2020072907
· 2020
[cited by applicant]
WO WO2020102741
· 2020
[cited by applicant]
WO WO2020180335
· 2020
[cited by applicant]
WO WO2020223133
· 2020
[cited by applicant]
WO WO2020014586A9
· 2021
[cited by applicant]
WO WO2021168083
· 2021
[cited by applicant]
WO WO2021211631A2
· 2023
[cited by applicant]
WO WO2023091961A2
· 2023
[cited by applicant]
“Omniligase™-1”, Product Information, Sigma-Aldrich. Downloaded from www.sigmaaldrich.com/deepweb/assets/sigmaaldrich/product/documents/218/840/sae0068pis.pdf on Sep. 8, 2023.
[cited by applicant]
“Single-Molecule Bioelectronics”, Columbia University, downloaded from https://bioeeweb.ee.columbia.edu/wordpress/single-molecule-bioelectronics/ on Sep. 11, 2023.
[cited by applicant]
Bailey, J. M. & Shively, J. E. Carboxy-terminal sequencing: formation and hydrolysis of C-terminal peptidylthiohydantoins. Biochemistry 29, 3145-56 (1990).
[cited by applicant]
Bottecchia, Cecilia, and Timothy Noël. “Photocatalytic Modification of Amino Acids, Peptides, and Proteins.”
[cited by applicant]
Bouilly, Delphine et al. “Single-Molecule Reaction Chemistry in Patterned Nanowells.”
[cited by applicant]
Chu et al.: Carboxylic Acids as a Traceless Activation Group for Conjugated Additions: A Three-Step Synthesis of (+/−)-Pregabalin. Journal of the American Chemical Society, Jul. 28, 2014, vol. 136, pp. 10886-10889, enti…
[cited by applicant]
Hellenkamp, Björn et al. “Precision and accuracy of single-molecule FRET measurements—a multi-laboratory benchmark study.”
[cited by applicant]
Horng, Jia-Cherng, and Ronald T. Raines. “Stereoelectronic effects on polyproline conformation.”
[cited by applicant]
Kakinoki, Sachiro, Yoshiaki Hirano, and Masahito Oka. “On the stability of polyproline-I and II structures of proline oligopeptides.”
[cited by applicant]
Kim et al., “C-terminal de novo sequencing of peptides using oxazolone-based derivation with bromine signature”, Analytical Biochemical, 419:211-216, 2011.
[cited by applicant]
Lee, Yoonhee et al. “Electrically Controllable Single-Point Covalent Functionalization of Spin-Cast Carbon-Nanotube Field-Effect Transistor Arrays.”
[cited by applicant]
MacDonald et al., One-Step Site-Specific Modification of Proteins with 2-Pyridinecarboxaldehyde Derivatives, A Dissertation submitted to University of California, 2016.
[cited by applicant]
Maiti, et al. Bifunctional aryloxyphosphoramidate prodrugs of 2′-C-Me-uridine: synthesis and anti-HCV activity. Organic & biomolecular chemistry vol. 14,37 (2016): 8743-8757.
[cited by applicant]
PCT/US2016/035716 International Search Report and Written Opinion dated Sep. 13, 2016.
[cited by applicant]
PCT/US2021/027155 International Preliminary Report on Patentability dated Oct. 13, 2023.
[cited by applicant]
PCT/US2022/079979 International Search Report and Written Opinion mailed Apr. 14, 2023.
[cited by applicant]
Rauniyar, et al., Isobaric Labeling-based relative quantification in shotgun proteomics. Journal of proteome. 2014.13, 5293-5309.
[cited by applicant]
Schuler, Benjamin et al. “Polyproline and the “spectroscopic ruler” revisited with single-molecule fluorescence.”
[cited by applicant]
Swaminathan et al., “A theoretical justification for single molecule peptide sequence,” PLoS computational biology, 11(2): e1004080 (2015).
[cited by applicant]
Van der Velde, Jasper H M et al. “A simple and versatile design concept for fluorophore derivatives with intramolecular photostabilization.”
[cited by applicant]
Vernick, Sefi et al. “Electrostatic melting in a single-molecule field-effect transistor with applications in genomic identification.”
[cited by applicant]
Zuo, Zhiwei et al. “Dual catalysis. Merging photoredox with nickel catalysis: coupling of α-carboxyl sp
[cited by applicant]
C387. Zuo, Zhiwei, and David W C MacMillan. “Decarboxylative arylation of α-amino acids via photoredox catalysis: a one-step conversion of biomass to drug pharmacophore.”
[cited by applicant]
Office Communication issued in Chinese Patent Application No. 201980049639.X, dated Nov. 28, 2023. English Translation.
[cited by applicant]
“The catalog for Molecular Probes”, downloaded from: web.archive.org/web/20101217092018/http://www.mobitec.de/probes/docs/sections/0101.pdf, available 2010.
[cited by applicant]
Abelin et al., “Mass Spectrometry Profiling of HLA-Associated Peptidomes in Mono-allelic Cells Enables More Accurate Epitope Prediction”,
[cited by applicant]
Aitken et al., “An Oxygen Scavenging System for Improvement of Dye Stability in Single-Molecule Fluorescence Experiments,”
[cited by applicant]
Alfaro et al., “The emerging landscape of single-molecule protein sequencing technologies”,
[cited by applicant]
Altman et al., “Enhanced photostability of cyanine fluorophores across the visible spectrum,”
[cited by applicant]
Altman et al., “Cyanine fluorophore derivatives with enhanced photostability,”
[cited by applicant]
Andrews et al., “A thermodynamic model for Nap1-histone interactions.”
[cited by applicant]
Antos et al., “Site-specific protein labeling via sortase-mediated transpeptidation”,
[cited by applicant]
Armbrecht et al., Single-cell protein profiling in microchambers with barcoded beads,
[cited by applicant]
Axelrod et al., “Cell-substrate contacts illuminated by total internal reflection fluorescence,”
[cited by applicant]
Backert & Kohlbacher, “Immunoinformatics and epitope prediction in the age of genomic medicine”,
[cited by applicant]
Baez et al., “Mass spectrometry in studies of protein thiol chemistry and signaling: opportunities and caveats”,
[cited by applicant]
Bailey and Shively, “Carboxy-terminal sequencing: formation and hydrolysis of C-terminal peptidylthiohydantoins,”
[cited by applicant]
Balister et al., “Percolation, connectivity, coverage and colouring of random geometric graphs”,
[cited by applicant]
Bamberger et al., “Protein Footprinting via Covalent Protein Painting Reveals Structural Changes of the Proteome in Alzheimer's Disease”,
[cited by applicant]
Baslé et al., “Protein Chemical Modification on Endogenous Amino Acids”,
[cited by applicant]
Bassani-Sternberg et al., “Mass spectrometry of human leukocyte antigen class I peptidomes reveals strong effects of protein abundance and turnover on antigen presentation”,
[cited by applicant]
Bendall et al., “Single-Cell Mass Cytometry of Differential Immune and Drug Responses Across a Human Hematopoietic Continuum,”
[cited by applicant]
Berg et al., “Peptide oligomers for holographic data storage,”
[cited by applicant]
Bethell et al., “Kinetics and mechanism of the Edman degradation,”
[cited by applicant]
Bhat et al., “The visible touch: in planta visualization of protein-protein interactions by fluorophore-based methods,”
[cited by applicant]
Biedka et al., “Reversible Click Chemistry Tag for Universal Proteome Sample Preparation for Top-Down and Bottom-Up Analysis,”
[cited by applicant]
Billingsley et al., “Single-molecule studies of DNA transcription using atomic force microscopy,”
[cited by applicant]
Bloom et al., “Decarboxylative alkylation for site-selective bioconjugation of native proteins via oxidation potentials,”
[cited by applicant]
Bonnet et al., “Amplifying Genetic Logic Gates,”
[cited by applicant]
Borgo et al., “Computer-aided design of a catalyst for Edman degradation utilizing substrate-assisted catalysis,”
[cited by applicant]
Bottecchia et al., “Photocatalytic modification of amino acids, peptides, and proteins”,
[cited by applicant]
Bradski et al., “OpenCV: an open-source computer vision library,” Dr. Dobb's Journal of Software Tools, 2000.
[cited by applicant]
Brandt et al., Quenching processes. www.rose-hulman.edu/˜brandt/Fluorescence/Quenching_processes.pdf, downloaded Feb. 18, 2016.
[cited by applicant]
Branton et al., “The potential and challenges of nanopore sequencing,”
[cited by applicant]
Braslavsky et al., “Sequence information can be obtained from single DNA molecules,”
[cited by applicant]
Brennick et al., “Neoepitopes as cancer immunotherapy targets: key challenges and opportunities”,
[cited by applicant]
Brewis et al., “Proteomics technologies for the global identification and quantification of proteins”,
[cited by applicant]
Brosseron et al., “Stepwise isolation of human peripheral erythrocytes, T lymphocytes, and monocytes for blood cell proteomics,”
[cited by applicant]
Brown et al., “Neo-antigens predicted by tumor genome meta-analysis correlate with increased patient survival.” Genome research, 24(5):743-50, 2014.
[cited by applicant]
Buschmann, & Bystrykh et al., “Levenshtein error-correcting barcodes for multiplexed DNA sequencing”,
[cited by applicant]
Cafferty et al., “Storage of information using small organic molecules,”
[cited by applicant]
Cang et al., “Giant suppression of photobleaching for single molecule detection via the Purcell effect,”
[cited by applicant]
Cannon et al., “A Dual-Mode Single-Molecule Fluorescence Assay for the Detection of Expanded CGG Repeats in Fragile X Syndrome,”
[cited by applicant]
Cao et al. “Selective Enrichment and Quantification of N-Terminal Glycine Peptides via Sortase A Mediated Ligation.”
[cited by applicant]
Caron et al., “A case for a human immuno-peptidome project consortium”,
[cited by applicant]
Caron et al., “Analysis of Major Histocompatibility Complex (MHC) Immunopeptidomes Using Mass Spectrometry”,
[cited by applicant]
Chalker et al., “Chemical Modification of Proteins at Cysteine: Opportunities in Chemistry and Biology,”
[cited by applicant]
Chang et al., “Manual solid phase sequence analysis of polypeptides using 4-N,N-dimethylaminoazobenzene 4′-isothiocyanate,”
[cited by applicant]
Chelius et al., Capture of peptides with N-terminal serine and threonine: a sequence-specific chemical method for Peptide mixture simplification.
[cited by applicant]
Chen et al., “An efficient and versatile approach for the preparation of a rhodamine B ester bioprobe library,”
[cited by applicant]
Chen et al., “Reactivity of functional groups on the protein surface: development of epoxide probes for protein labeling.”
[cited by applicant]
Chen et al., “Selective chemical labeling of proteins”,
[cited by applicant]
Chen et al., “Spatially resolved, highly multiplexed RNA profiling in single cells”,
[cited by applicant]
Choi et al., “Core-shell silica nanoparticles as fluorescent labels for nanomedicine,”
[cited by applicant]
Church et al., “Next-Generation Digital Information Storage in DNA.”
[cited by applicant]
Clement et al., “The Dendritic Cell Major Histocompatibility Complex II (MHC II) Peptidome Derives from a Variety of Processing Pathways and Includes Peptides with a Broad Spectrum of HLA-DM Sensitivity.”
[cited by applicant]
Cline et al., “Kinetics and mechanisms of the aminolysis of N-hydroxysuccinimide esters in aqueous buffers,”
[cited by applicant]
Cockrill et al., “Efficient micro-recovery and guanidination of peptides directly from MALDI target spots,”
[cited by applicant]
Cohen et al., “Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c,”
[cited by applicant]
Colombani et al., “Polymerization kinetics: monitoring monomer conversion using an internal standard and the key role of sample to.”
[cited by applicant]
Co-pending U.S. Appl. No. 17/491,485, inventors Marcotte; Edward et al., filed Sep. 30, 2021.
[cited by applicant]
Co-pending U.S. Appl. No. 17/738,281, inventors Marcotte; Edward et al., filed May 6, 2022.
[cited by applicant]
Co-pending U.S. Appl. No. 17/964,201, inventors Somekh; Tal et al., filed Oct. 12, 2022.
[cited by applicant]
Cordes and Blum, “Opportunities and challenges in single-molecule and single-particle fluorescence microscopy for mechanistic studies of chemical reactions,”
[cited by applicant]
Cordes et al., “On the Mechanism of Trolox as Antiblinking and Antibleaching Reagent,”
[cited by applicant]
Croop et al., “Single-shot, shadowless total internal reflection fluorescence microscopy via annular fiber bundle”,
[cited by applicant]
Cuppoletti et al., “Oligomeric Fluorescent Labels for DNA,”
[cited by applicant]
Czaplyski et al., “Substituent effects on the turn-on kinetics of rhodamine-based fluorescent pH probes,”
[cited by applicant]
Da Costa et al., “How low can you go? A current perspective on low-abundance proteomics,”
[cited by applicant]
D'Amici et al., “Red blood cell storage in SAGM and AS3: a comparison through the membrane two-dimensional electrophoresis proteome,”
[cited by applicant]
Declaration of Dr. Edward Marcotte filed in U.S. Appl. No. 14/128,247, filed Jul. 7, 2016.
[cited by applicant]
Declaration of Dr. Edward Marcotte filed in U.S. Appl. No. 14/128,247, filed Sep. 2, 2016.
[cited by applicant]
Declaration of Dr. Jagannath Swaminathan filed in U.S. Appl. No. 14/128,247, filed Jan. 26, 2016.
[cited by applicant]
Dempsey et al., “Evaluation of fluorophores for optimal performance in localization-based super-resolution imaging,”
[cited by applicant]
Dixon et al., “Reversible blocking of amino groups with citraconic anhydride”,
[cited by applicant]
Doll et al., “Visualization of Protein-Specific Glycosylation inside Living Cells”,
[cited by applicant]
Dong et al., “Label-free quantitation of glycated hemoglobin in single red blood cells by transient absorption microscopy and phasor analysis”,
[cited by applicant]
Donnert et al., “Major signal increase in fluorescence microscopy through dark-state relaxation,”
[cited by applicant]
Doolittle et al., “A simple solid-phase amino acid sequencer employing a thioacetylation stepwise degradation procedure”,
[cited by applicant]
Duan et al., “ProC-TEL: Profiling of Protein C-Termini by Enzymatic Labeling”,
[cited by applicant]
Dudley et al., Adoptive-cell-transfer therapy for the treatment of patients with cancer,
[cited by applicant]
Duffy et al., “Clinical use of biomarkers in breast cancer: Updated guidelines from the European Group on Tumor Markers (EGTM)”,
[cited by applicant]
Dunn et al., “Techniques for phosphopeptide enrichment prior to analysis by mass spectrometry”,
[cited by applicant]
Edman et al., “A Protein Sequenator,”
[cited by applicant]
Edman et al., “Method for determination of the amino acid sequence in peptides,”
[cited by applicant]
Edman et al., “A method for the determination of amino acid sequence in peptides,”
[cited by applicant]
Edman et al., “Preparation of Phenyl Thiohydantoins from Some Natural Amino Acids”,
[cited by applicant]
Egloff et al., Engineered peptide barcodes for in-depth analyses of binding protein libraries,
[cited by applicant]
Eid et al., “Real-Time DNA Sequencing from Single Polymerase Molecules,”
[cited by applicant]
Eliason et al., “Temperature effect on reaction rates.”
[cited by applicant]
Ellson et al., Graphviz and Dynagraph—Static and Dynamic Graph Drawing Tools,
[cited by applicant]
Eng et al., “An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database”,
[cited by applicant]
EP19834092.9 extended European Search Report dated Mar. 18, 2022.
[cited by applicant]
EP19849103.7 Extended European Search Report dated May 16, 2022.
[cited by applicant]
EP19868673.5 Extended European Search Report dated Jul. 19, 2022.
[cited by applicant]
EP20150854171 European Search Report dated Feb. 12, 2018.
[cited by applicant]
EP20150854171 Extended European Search Report dated Jun. 6, 2018.
[cited by applicant]
EP20180215779 European Search Report dated Jul. 26, 2019.
[cited by applicant]
Erdős & Rényi et al., “On the strength of connectedness of a random graph”,
[cited by applicant]
European Search Report issued in European Patent Application No. 19849848.6 mailed Sep. 1, 2022.
[cited by applicant]
Feng et al., “Imaging Neuronal Subsets in Transgenic Mice Expressing Multiple Spectral Variants of GFP,”
[cited by applicant]
Fina et al., “The Alpha Effect. A Review”
[cited by applicant]
Fields et al., “The interplay of biology and technology,”
[cited by applicant]
Fredkin et al., “Trie memory,”
[cited by applicant]
Frey et al., “Chemical Derivatization of Peptide Carboxyl Groups for Highly Efficient Electron Transfer Dissociation,”
[cited by applicant]
Fukuzaki et al., “Adsorption of protein onto stainless-steel surfaces,”
[cited by applicant]
Gajer et al., “A Multi-dimensional Approach to Force-Directed Layouts of Large Graphs”,
[cited by applicant]
Garcia-Parajo et al., “The nature of fluorescence emission in the red fluorescent protein DsRed, revealed by single-molecule detection,”
[cited by applicant]
Garreau et al., “C-Terminal Bioconjugation of Peptides through Photoredox Catalyzed Decarboxylative Alkynylation,”
[cited by applicant]
Gawad et al., “Single-cell genome sequencing: current state of the science”,
[cited by applicant]
Ghaemmaghami et al., “Global analysis of protein expression in yeast,”
[cited by applicant]
Gilmore et al., “N-Terminal Protein Modification through a Biomimetic Transamination Reaction‡,”
[cited by applicant]
Gnjatic et al., “Identifying baseline immune-related biomarkers to predict clinical outcome of immunotherapy”,
[cited by applicant]
Godkin et al., “Characterization of novel HLA-DR11-restricted HCV epitopes reveals both qualitative and quantitative differences in HCV-specific CD4+ T cell responses in chronically infected and non-viremic patients”,
[cited by applicant]
Goodman et al., Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers,
[cited by applicant]
Gooley et al., “Glycosylation sites identified by detection of glycosylated amino acids released from Edman degradation: The identification of Xaa-Pro-Xaa-Xaa as a motif for Thr-O-glycosylation,”
[cited by applicant]
Gullberg et al., “A sense of closeness: protein detection by proximity ligation”,
[cited by applicant]
Gyarmati et al., “Reversible disulphide formation in polymer networks: A versatile functional group from synthesis to applications”,
[cited by applicant]
György et al., “Citrullination: a posttranslational modification in health and disease”,
[cited by applicant]
Haab et al., “Applications of antibody array platforms,”
[cited by applicant]
Haensch et al., “Chemical modification of self-assembled silane based monolayers by surface reactions”,
[cited by applicant]
Hamada et al., “A novel N-terminal degradation reaction of peptides via N-amidination”
[cited by applicant]
Han et al., “Current developments in stepwise edman degradation of peptides and proteins,”
[cited by applicant]
Hanay et al., “Single-protein nanomechanical mass spectrometry in real time,”
[cited by applicant]
Haralambidis et al., “The preparation of polyamide-oligonucleotide probes containing multiple non-radioactive labels”,
[cited by applicant]
Harris et al., “Single-Molecule DNA Sequencing of a Viral Genome,”
[cited by applicant]
Harris et al., “Immuno-oncology combinations: raising the tail of the survival curve”,
[cited by applicant]
Hartmann et al., “A universal live cell barcoding-platform for multiplexed human single cell analysis,”
[cited by applicant]
Havugimana et al., “A Census of Human Soluble Protein Complexes,”
[cited by applicant]
Herbrink et al., “Solid phase Edman degradation. High yield attachment of tryptic protein fragments to aminated supports,”
[cited by applicant]
Hermanson et al., “Bioconjugate Techniques: Bioconjugate Techniques”,
[cited by applicant]
Hernandez 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
[cited by applicant]
Higgins et al., “Kinetic analysis of the nonenzymatic glycosylation of hemoglobin,”
[cited by applicant]
Hoebe et al., “Controlled light-exposure microscopy reduces photobleaching and phototoxicity in fluorescence live-cell imaging,”
[cited by applicant]
Hong et al., “ProtSeq: Toward high-throughput, single-molecule protein sequencing via amino acid conversion into DNA barcodes”,
[cited by applicant]
Horton et al., “A Highly Reactive Colored Reagent with Selectivity for the Tryptophan Residue in Proteins. 2-Hydroxy-5-nitrobenzyl Bromide
[cited by applicant]
Howard et al., “Solid-Phase Peptide Capture and Release of Bulk and Single-Molecule Proteomics”,
[cited by applicant]
Huang et al., “Super resolution fluorescence microscopy,”
[cited by applicant]
Huang et al., “Three-Dimensional Super-Resolution Imaging by Stochastic Optical Reconstruction Microscopy,”
[cited by applicant]
Hughes et al., “Single-cell western blotting”,
[cited by applicant]
Hwang et al., “Identification of Missing Proteins in Human Olfactory Epithelial Tissue by Liquid Chromatography-Tandem Mass Spectrometry”,
[cited by applicant]
Imakyure et al., “A fluorogenic reagent for amino acids in liquid chromatography, 4-(2-cyanoisoindolyl)phenylisothiocyanate,”
[cited by applicant]
Inglis et al., “Chemical procedures for C-terminal sequencing of peptides and proteins,”
[cited by applicant]
Ingolia et al., “Genome-Wide Analysis in Vivo of Translation with Nucleotide Resolution Using Ribosome Profiling,”
[cited by applicant]
International Search Report and Written Opinion issued in PCT/US2022/017642 on Jul. 19, 2022.
[cited by applicant]
International Search Report and Written Opinion issued in PCT/US2022/031022 on Aug. 19, 2022.
[cited by applicant]
International Search Report and Written Opinion issued in PCT/US2022/74750 on Nov. 7, 2022.
[cited by applicant]
Ireland et al., “Double Coupling Edman Chemistry for High-Sensitivity Automated Protein Sequencing,”
[cited by applicant]
Isidro-Llobet et al., “Amino acid-protecting groups,”
[cited by applicant]
Jain et al., “Stoichiometry and assembly of mTOR complexes revealed by single-molecule pulldown,”
[cited by applicant]
Jameson et al., “Fluorescence Polarization/Anisotropy in Diagnostics and Imaging,” Chem. Rev., 110 (5):2685-2708, 2010.
[cited by applicant]
Javitt et al., “The proteasome regulator PSME4 drives immune evasion and abrogates anti- tumor immunity in NSCLC”,
[cited by applicant]
Jin et al., “Recent advances in dynamic covalent chemistry”,
[cited by applicant]
Jin et al., “Study on New Edman-type Reagents,”
[cited by applicant]
Johnson et al. “Reversible macrocyclization of peptides with a conjugate acceptor”,
[cited by applicant]
Joo et al., “Advances in single-molecule fluorescence methods for molecular biology,”
[cited by applicant]
Julka et al., “Quantification in proteomics through stable isotope coding: a review,”
[cited by applicant]
Jungmann et al., “Quantitative super-resolution imaging with qPAINT,”
[cited by applicant]
Kamada and Kawai et al., “An algorithm for drawing general undirected graphs”,
[cited by applicant]
Kamada and Soderberg., “Flow-assisted assembly of nanostructured protein microfibers”,
[cited by applicant]
Katritzky et al., “Fluorescent labeling of peptides on solid phase,”
[cited by applicant]
Kelly et al., “Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma,”
[cited by applicant]
Keough et al., “Derivatization procedures to facilitate de novo sequencing of lysine-terminated tryptic peptides using postsource decay matrix-assisted laser desorption/ionization mass spectrometry,”
[cited by applicant]
Kim et al., “C-terminal de novo sequencing of peptides using oxazolone-based derivatization with bromine signature”,
[cited by applicant]
Kinraide et al., “Use of a Gouy-Chapman-Stern model for membrane-surface electrical potential to interpret some features of mineral rhizotoxicity,”
[cited by applicant]
Klement et al., “Enrichment of O-GlcNAc modified proteins by the periodate oxidation-hydrazide resin capture approach”,
[cited by applicant]
Ko et al., “Enhanced electron transfer dissociation of peptides modified at C-terminus with fixed charges,”
[cited by applicant]
Koide et al., “Development of NIR fluorescent dyes based on Si-rhodamine for in vivo imaging,”
[cited by applicant]
Konry et al., “Droplet-based microfluidic platforms for single T cell secretion analysis of IL-10 cytokine,”
[cited by applicant]
Kool et al., “Fast alpha nucleophiles: structures that undergo rapid hydrazone/oxime formation at neutral pH”,
[cited by applicant]
Koos et al., “Analysis of protein interactions in situ by proximity ligation assays,”
[cited by applicant]
Kovalova et al., “Stepwise triple-click functionalization of synthetic peptides”,
[cited by applicant]
Krusemark et al., “Complete chemical modification of amine and acid functional groups of peptides and small proteins,”
[cited by applicant]
Kuyama et al., “An approach to quantitative proteome analysis by labeling tryptophan residues,”
[cited by applicant]
Lakowicz et al., “Mechanisms and Dynamics of Fluorescence Quenching,” In:
[cited by applicant]
Lamesch et al., “hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes,”
[cited by applicant]
Lang et al., “Cellular incorporation of unnatural amino acids and bioorthogonal labeling of proteins”,
[cited by applicant]
Laursen et al., “Solid-Phase Edman Degradation: An Automatic Peptide Sequencer,”
[cited by applicant]
Lee et al., “A Simple Outline of Methods for Protein Isolation and Purification”,
[cited by applicant]
Lee et al., “Evidence of preserved collagen in an Early Jurassic sauropodomorph dinosaur revealed by synchrotron FTIR microspectroscopy,”
[cited by applicant]
Lee et al., “Update on Tumor Neoantigens and Their Utility: Why It Is Good to Be Different”,
[cited by applicant]
Leigh-Smith et al., “Blood boosting,”
[cited by applicant]
Li et al. “Synthesis and biological evaluation of nonsymmetrical aromatic disulfides as novel inhibitors of acetohydroxyacid synthase,”
[cited by applicant]
Li et al., “Selective labeling of histidine by a designed fluorescein-based probe,”
[cited by applicant]
Li et al., “Constrained De Novo Sequencing of neo-Epitope Peptides using Tandem Mass Spectrometry”,
[cited by applicant]
Li et al., “N-terminal α-amino group modification of antibodies using a site-selective click chemistry method,”
[cited by applicant]
Lin et al., “Efforts and Challenges in Engineering the Genetic Code”,
[cited by applicant]
Lin et al., “Examining histone posttranslational modification patterns by high-resolution mass spectrometry”,
[cited by applicant]
Liu et al., “On the dependency of cellular protein levels on mRNA abundance,”
[cited by applicant]
Lo et al., “Quantification of protein levels in single living cells,”
[cited by applicant]
Lotze et al., “Peptide-tags for site-specific protein labelling in vitro and in vivo”,
[cited by applicant]
Luchowski et al., “Single molecule studies of multiple-fluorophore labeled antibodies. Effect of homo-FRET on the number of photons available before photobleaching,”
[cited by applicant]
Lukinavious et al., “A near-infrared fluorophore for live-cell super-resolution microscopy of cellular proteins,”
[cited by applicant]
Lyon et al., “Self-hydrolyzing maleimides improve the stability and pharmacological properties of antibody-drug conjugates,”
[cited by applicant]
Macbeath et al., “Printing small molecules as microarrays and detecting protein-ligand interactions en masse,”
[cited by applicant]
MacDonald et al., “One-step site-specific modification of native proteins with 2-pyridinecarboxyaldehydes,”
[cited by applicant]
Maiti et al., “Bifunctional aryloxyphosphoramidate prodrugs of 2′-C-Me-uridine: synthesis and anti-HCV activity”,
[cited by applicant]
Mallam et al., “Systematic discovery of endogenous human ribonucleoprotein complexes,”
[cited by applicant]
Margulies et al., “Genome sequencing in microfabricated high-density picolitre reactors”,
[cited by applicant]
Martins et al., “Selective Recognition of Amino Acids and Peptides by Small Supramolecular Receptors”,
[cited by applicant]
Martos-Maldonado et al., “Selective N-terminal acylation of peptides and proteins with a Gly-His tag sequence”,
[cited by applicant]
Matsunaga et al., “Proton: a major factor for the racemization and the dehydration at the cyclization/cleavage stage in the Edman sequencing method,”
[cited by applicant]
Maude et al., “Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia”,
[cited by applicant]
Mazutis et al., “Single-cell analysis and sorting using droplet-based microfluidics,”
[cited by applicant]
Mazzone et al., “Evaluating Molecular Biomarkers for the Early Detection of Lung Cancer: When Is a Biomarker Ready for Clinical Use? An Official American Thoracic Society Policy Statement.”
[cited by applicant]
Mcalpine et al., “Visualizing Functional Group Distribution in Solid-Support Beads by Using Optical Analysis,”
[cited by applicant]
Merrifield et al., Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide,
[cited by applicant]
Millington et al., “Aryl hydrazides as linkers for solid phase synthesis which are cleavable under mild oxidative conditions,”
[cited by applicant]
Miyamoto et al., Peptide barcoding for establishment of new types of genotype-phenotype linkages, PLOS one, Apr. 23, 2019.
[cited by applicant]
Miyashita et al., “Attomole level protein sequencing by Edman degradation coupled with accelerator mass spectrometry,”
[cited by applicant]
Moffett et al., “Tryptophan and the immune response,”
[cited by applicant]
Mohanty et al., “Advancing cell biology and functional genomics in maize using fluorescent protein-tagged lines,”
[cited by applicant]
Momaya et al., “Performance-enhancing substances in sports: a review of the literature”
[cited by applicant]
Monfort et al., “Plasticizers excreted in urine: indication of autologous blood transfusion in sports,”
[cited by applicant]
Müller et al., Current Strategies for the Identification of Immunogenic Epitopes of Tumor Antigens,
[cited by applicant]
Muramoto et al., “The application of fluorescein isothiocyanate and high-performance liquid chromatography for the microsequencing of proteins and peptides,”
[cited by applicant]
Murata et al., “Solid-phase synthesis of protein-polymers on reversible immobilization supports”,
[cited by applicant]
Nagaraj et al., “Deep proteome and transcriptome mapping of a human cancer cell line,”
[cited by applicant]
Nakajima et al., “Mass spectrometry-based sequencing of protein C-terminal peptide using α-carboxyl group-specific derivatization and COOH capturing”,
[cited by applicant]
Neefjes et al., “Towards a systems understanding of MHC class I and MHC class II antigen presentation”,
[cited by applicant]
Ng et al., “Data storage using peptide sequences”,
[cited by applicant]
Nguyen et al., “Butelase-mediated cyclization and ligation of peptides and proteins”,
[cited by applicant]