Multiplex Protein Detection with DNA Readout Via Mass Spectrometry

Overview

Journal N Biotechnol

Publisher Elsevier

Specialties Biomedical Engineering
Biotechnology
Molecular Biology

Date 2012 Dec 4

PMID 23201185

Citations 1

Authors

James Flanigon

Masood Kamali-Moghaddam

Ian Burbulis

Carla Annink

Martin Steffen

Paul Oeth

Roger Brent

Dirk Van Den Boom

Ulf Landegren

Charles Cantor

Affiliations

Soon will be listed here.

Abstract

Multiplex protein quantification has been constrained by issues of assay specificity, sensitivity and throughput. This research presents a novel approach that overcomes these limitations using antibody-oligonucleotide conjugates for immuno-polymerase chain reaction (immuno-PCR) or proximity ligation, coupled with competitive PCR and MALDI-TOF mass spectrometry. Employing these combinations of technologies, we demonstrate multiplex detection and quantification of up to eight proteins, spanning wide dynamic ranges from femtomolar concentrations, using only microliter sample volumes.

Citing Articles

Multiplex protein profiling method for extracellular vesicle protein detection.

Sun L, Meckes Jr D Sci Rep. 2021; 11(1):12477.

PMID: 34127763 PMC: 8203679. DOI: 10.1038/s41598-021-92012-6.

References

Gustafsdottir S, Nordengrahn A, Fredriksson S, Wallgren P, Rivera E, Schallmeiner E . Detection of individual microbial pathogens by proximity ligation. Clin Chem. 2006; 52(6):1152-60. DOI: 10.1373/clinchem.2005.065847. View

Edwards J, Ruparel H, Ju J . Mass-spectrometry DNA sequencing. Mutat Res. 2005; 573(1-2):3-12. DOI: 10.1016/j.mrfmmm.2004.07.021. View

Saito K, Kobayashi D, Sasaki M, Araake H, Kida T, Yagihashi A . Detection of human serum tumor necrosis factor-alpha in healthy donors, using a highly sensitive immuno-PCR assay. Clin Chem. 1999; 45(5):665-9. View

Darmanis S, Nong R, Vanelid J, Siegbahn A, Ericsson O, Fredriksson S . ProteinSeq: high-performance proteomic analyses by proximity ligation and next generation sequencing. PLoS One. 2011; 6(9):e25583. PMC: 3183061. DOI: 10.1371/journal.pone.0025583. View

Ding C, Cantor C . A high-throughput gene expression analysis technique using competitive PCR and matrix-assisted laser desorption ionization time-of-flight MS. Proc Natl Acad Sci U S A. 2003; 100(6):3059-64. PMC: 152246. DOI: 10.1073/pnas.0630494100. View

Niemeyer C, Adler M, Wacker R . Detecting antigens by quantitative immuno-PCR. Nat Protoc. 2007; 2(8):1918-30. DOI: 10.1038/nprot.2007.267. View

Elvidge G, Price T, Glenny L, Ragoussis J . Development and evaluation of real competitive PCR for high-throughput quantitative applications. Anal Biochem. 2005; 339(2):231-41. DOI: 10.1016/j.ab.2005.01.040. View

Adler M, Wacker R, Niemeyer C . Sensitivity by combination: immuno-PCR and related technologies. Analyst. 2008; 133(6):702-18. DOI: 10.1039/b718587c. View

Kingsmore S . Multiplexed protein measurement: technologies and applications of protein and antibody arrays. Nat Rev Drug Discov. 2006; 5(4):310-20. PMC: 1780251. DOI: 10.1038/nrd2006. View

10.

Kamali-Moghaddam M, Pettersson F, Wu D, Englund H, Darmanis S, Lord A . Sensitive detection of Aβ protofibrils by proximity ligation--relevance for Alzheimer's disease. BMC Neurosci. 2010; 11:124. PMC: 2959092. DOI: 10.1186/1471-2202-11-124. View

11.

Landegren U, Vanelid J, Hammond M, Nong R, Wu D, Ulleras E . Opportunities for sensitive plasma proteome analysis. Anal Chem. 2012; 84(4):1824-30. DOI: 10.1021/ac2032222. View

12.

Schallmeiner E, Oksanen E, Ericsson O, Spangberg L, Eriksson S, Stenman U . Sensitive protein detection via triple-binder proximity ligation assays. Nat Methods. 2006; 4(2):135-7. DOI: 10.1038/nmeth974. View

13.

Sano T, Smith C, Cantor C . Immuno-PCR: very sensitive antigen detection by means of specific antibody-DNA conjugates. Science. 1992; 258(5079):120-2. DOI: 10.1126/science.1439758. View

14.

Fredriksson S, Dixon W, Ji H, Koong A, Mindrinos M, Davis R . Multiplexed protein detection by proximity ligation for cancer biomarker validation. Nat Methods. 2007; 4(4):327-9. DOI: 10.1038/nmeth1020. View

15.

Anderson N, Anderson N . The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics. 2002; 1(11):845-67. DOI: 10.1074/mcp.r200007-mcp200. View

16.

Jurinke C, Van Den Boom D, Cantor C, Koster H . The use of MassARRAY technology for high throughput genotyping. Adv Biochem Eng Biotechnol. 2002; 77:57-74. DOI: 10.1007/3-540-45713-5_4. View

17.

Braun A, Little D, Koster H . Detecting CFTR gene mutations by using primer oligo base extension and mass spectrometry. Clin Chem. 1997; 43(7):1151-8. View

18.

Darmanis S, Nong R, Hammond M, Gu J, Alderborn A, Vanelid J . Sensitive plasma protein analysis by microparticle-based proximity ligation assays. Mol Cell Proteomics. 2009; 9(2):327-35. PMC: 2830843. DOI: 10.1074/mcp.M900248-MCP200. View

19.

Burbulis I, Yamaguchi K, Gordon A, Carlson R, Brent R . Using protein-DNA chimeras to detect and count small numbers of molecules. Nat Methods. 2005; 2(1):31-7. DOI: 10.1038/nmeth729. View

20.

Hahlbrock K . Absolute mRNA quantification using the polymerase chain reaction (PCR). A novel approach by a PCR aided transcript titration assay (PATTY). Nucleic Acids Res. 1989; 17(22):9437-46. PMC: 335144. DOI: 10.1093/nar/17.22.9437. View