- Crompton P.D.
- Kayala M.A.
- Traore B.
- Kayentao K.
- Ongoiba A.
- Weiss G.E.
- Molina D.M.
- Burk C.R.
- Waisberg M.
- Jasinskas A.
- Tan X.
- Doumbo S.
- Doumtabe D.
- Kone Y.
- Narum D.L.
- Liang X.
- Doumbo O.K.
- Miller L.H.
- Doolan D.L.
- Baldi P.
- Felgner P.L.
- Pierce S.K.
- Lessa-Aquino C.
- Rodrigues C.B.
- Pablo J.
- Sasaki R.
- Jasinskas A.
- Liang L.
- Wunder E.A.
- Ribeiro G.S.
- Vigil A.
- Galler R.
- Molina D.
- Liang X.
- Reis M.G.
- Ko A.I.
- Medeiros M.A.
- Felgner P.L.
EXPERIMENTAL PROCEDURES
Peptide Microarray Content Design
- Aslett M.
- Aurrecoechea C.
- Berriman M.
- Brestelli J.
- Brunk B.P.
- Carrington M.
- Depledge D.P.
- Fischer S.
- Gajria B.
- Gao X.
- Gardner M.J.
- Gingle A.
- Grant G.
- Harb O.S.
- Heiges M.
- Hertz-Fowler C.
- Houston R.
- Innamorato F.
- Iodice J.
- Kissinger J.C.
- Kraemer E.
- Li W.
- Logan F.J.
- Miller J.A.
- Mitra S.
- Myler P.J.
- Nayak V.
- Pennington C.
- Phan I.
- Pinney D.F.
- Ramasamy G.
- Rogers M.B.
- Roos D.S.
- Ross C.
- Sivam D.
- Smith D.F.
- Srinivasamoorthy G.
- Stoeckert Jr., C.J.
- Subramanian S.
- Thibodeau R.
- Tivey A.
- Treatman C.
- Velarde G.
- Wang H.
- Dos Santos S.
- Freitas L.M.
- Lobo F.P.
- Rodrigues-Luiz G.F.
- de Oliveira Mendes T.A.
- Oliveira A.C.S.
- Andrade L.O.
- Chiari E.
- Gazzinelli R.T.
- Teixeira S.M.R.
- Fujiwara R.T.
- Bartholomeu D.C.
Protein Set | Description | No. of Peptides | Positive Peptides | |
---|---|---|---|---|
Average signal in all chips | In single chip | |||
Group 1 | Proteins picked randomly from the proteome | 38,664 | 50 (0.13%) | 23.5 ± 17.2 |
Group 2 | Proteins ranked with a bioinformatics method | 37,773 | 317 (0.84%) | 133.25 ± 38.54 |
Group 3 | Proteins from MASP family | 65,808 | 797 (1.21%) | 399.75 ± 219.3 |
Group 4 | Proteins with previous seroreactivity evidence | 32,372 | 848 (2.62%) | 484.75 ± 76.3 |
Derivatization of Synthesis Slides
Peptide Arrays Synthesis
Human Sera Samples
Assays with Peptide Arrays and Data Acquisition
Peptide Mapping, Data Normalization, Signal Smoothing and Negative Subtraction

Epitope Mapping Performance Analysis
Sensitivity, Positive Predictive Value, and Cut-Off Definition

Definition of Antigenic Regions
Analysis of Technical Reproducibility and Biological Variability

ELISA Validation of TSSA Antigen

Data Availability
RESULTS
Design of a High-density Peptide Chip for Screening and Mapping B-cell Epitopes in Chagas Disease
Performance of the HD-Chip Platform: Mapping of Known Chagas Disease Epitopes
High Technical Reproducibility Expedites Studies on the Diversity of B-Cell Responses Using HD-Chips
High Resolution Mapping of Reactive Epitopes
- Risso M.G.
- Sartor P.A.
- Burgos J.M.
- Briceño L.
- Rodríguez E.M.
- Guhl F.
- Chavez O.T.
- Espinoza B.
- Monteón V.M.
- Russomando G.
- Schijman A.G.
- Bottasso O.A.
- Leguizamón M.S.
Discovery and Fine Mapping of Novel Antigenic Determinants
- El-Sayed N.M.
- Myler P.J.
- Bartholomeu D.C.
- Nilsson D.
- Aggarwal G.
- Tran A.-N.
- Ghedin E.
- Worthey E.A.
- Delcher A.L.
- Blandin G.
- Westenberger S.J.
- Caler E.
- Cerqueira G.C.
- Branche C.
- Haas B.
- Anupama A.
- Arner E.
- Aslund L.
- Attipoe P.
- Bontempi E.
- Bringaud F.
- Burton P.
- Cadag E.
- Campbell D.A.
- Carrington M.
- Crabtree J.
- Darban H.
- da Silveira J.F.
- de Jong P.
- Edwards K.
- Englund P.T.
- Fazelina G.
- Feldblyum T.
- Ferella M.
- Frasch A.C.
- Gull K.
- Horn D.
- Hou L.
- Huang Y.
- Kindlund E.
- Klingbeil M.
- Kluge S.
- Koo H.
- Lacerda D.
- Levin M.J.
- Lorenzi H.
- Louie T.
- Machado C.R.
- McCulloch R.
- McKenna A.
- Mizuno Y.
- Mottram J.C.
- Nelson S.
- Ochaya S.
- Osoegawa K.
- Pai G.
- Parsons M.
- Pentony M.
- Pettersson U.
- Pop M.
- Ramirez J.L.
- Rinta J.
- Robertson L.
- Salzberg S.L.
- Sanchez D.O.
- Seyler A.
- Sharma R.
- Shetty J.
- Simpson A.J.
- Sisk E.
- Tammi M.T.
- Tarleton R.
- Teixeira S.
- Aken S.
- Van, Vogt C.
- Ward P.N.
- Wickstead B.
- Wortman J.
- White O.
- Fraser C.M.
- Stuart K.D.
- Andersson B.
Protein Set | Description | Number | Positive Proteins | |
---|---|---|---|---|
Average signal in all chips | In a single chip | |||
Group 1 | Proteins picked randomly from the proteome | 50 | 5 (10%) | 3 ± 2.1 |
Group 2 | Proteins ranked with a bioinformatics method | 99 | 21 (21.21%) | 10 ± 1.4 |
Group 3 | Proteins from MASP family | 232 | 70 (30.17%) | 46.25 ± 11.6 |
Group 4 | Proteins with previous seroreactivity evidence | 68 | 24 (35.29%) | 16.5 ± 2.9 |
DISCUSSION
- Davies D.H.
- Liang X.
- Hernandez J.E.
- Randall A.
- Hirst S.
- Mu Y.
- Romero K.M.
- Nguyen T.T.
- Kalantari-Dehaghi M.
- Crotty S.
- Baldi P.
- Villarreal L.P.
- Felgner P.L.
- Liang L.
- Tan X.
- Juarez S.
- Villaverde H.
- Pablo J.
- Nakajima-Sasaki R.
- Gotuzzo E.
- Saito M.
- Hermanson G.
- Molina D.
- Felgner S.
- Morrow W.J.W.
- Liang X.
- Gilman R.H.
- Davies D.H.
- Tsolis R.M.
- Vinetz J.M.
- Felgner P.L.
- Crompton P.D.
- Kayala M.A.
- Traore B.
- Kayentao K.
- Ongoiba A.
- Weiss G.E.
- Molina D.M.
- Burk C.R.
- Waisberg M.
- Jasinskas A.
- Tan X.
- Doumbo S.
- Doumtabe D.
- Kone Y.
- Narum D.L.
- Liang X.
- Doumbo O.K.
- Miller L.H.
- Doolan D.L.
- Baldi P.
- Felgner P.L.
- Pierce S.K.
- Zingales B.
- Miles M.A.
- Campbell D.A.
- Tibayrenc M.
- Macedo A.M.
- Teixeira M.M.G.
- Schijman A.G.
- Llewellyn M.S.
- Lages-Silva E.
- Machado C.R.
- Andrade S.G.
- Sturm N.R.
Acknowledgments
Supplementary Material
REFERENCES
- Lambda-display: a powerful tool for antigen discovery.Molecules. 2011; 16: 3089-3105
- Epitope discovery using peptide libraries displayed on phage.Trends Biotechnol. 1994; 12: 262-267
- Protein microarrays for highly parallel detection and quantitation of specific proteins and antibodies in complex solutions.Genome Biol. 2001; 2research0004
- Peptide microarrays for serum antibody diagnostics.Methods Mol. Biol. 2009; 509: 123-134
- Immune epitope database analysis resource.Nucleic Acids Res. 2012; 40: W525-W530
- From protein microarrays to diagnostic antigen discovery: a study of the pathogen Francisella tularensis.Bioinformatics. 2007; 23: i508-i518
- Pattern recognition in pulmonary tuberculosis defined by high content peptide microarray chip analysis representing 61 proteins from M. tuberculosis.PLoS One. 2008; 3: e3840
- Dynamic antibody responses tuberculosis to the Mycobacterium tuberculosis proteome.Proc. Natl. Acad. Sci. U.S.A. 2010; 107: 14703-14708
- A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray.Proc. Natl. Acad. Sci. U.S.A. 2010; 107: 6958-6963
- Plasmodium immunomics.Int. J. Parasitol. 2011; 41: 3-20
- Profiling the humoral immune response of acute and chronic Q fever by protein microarray.Mol. Cell. Proteomics. 2011; 10M110.006304
- Identification of seroreactive proteins of Leptospira interrogans serovar copenhageni using a high-density protein microarray approach.PLoS Negl. Trop. Dis. 2013; 7: e2499
- Whole CMV proteome pattern recognition analysis after HSCT identifies unique epitope targets associated with the CMV status.PLoS One. 2014; 9: e89648
- Light-directed, spatially addressable parallel chemical synthesis.Science. 1991; 251: 767-773
- Individually addressable parallel peptide synthesis on microchips.Nat. Biotechnol. 2002; 20: 922-926
- High-resolution mapping of linear antibody epitopes using ultrahigh-density peptide microarrays.Mol. Cell. Proteomics. 2012; 11: 1790-1800
- Proteome-wide epitope mapping of antibodies using ultra-dense peptide arrays.Mol. Cell. Proteomics. 2014; 13: 1585-1597
- Identification and mapping of linear antibody epitopes in human serum albumin using high-density peptide arrays.PLoS One. 2013; 8: e68902
- Chagas disease.Lancet. 2010; 375: 1388-1402
- Identification of a Trypanosoma cruzi antigen that is shed during the acute phase of Chagas' disease.Mol. Biochem. Parasitol. 1989; 34: 221-228
- Assay for detection of Trypanosoma cruzi antibodies in human sera based on reaction with synthetic peptides.J. Clin. Microbiol. 1991; 29: 2034-2037
- Evaluation of a recombinant Trypanosoma cruzi mucin-like antigen for serodiagnosis of Chagas' disease.Clin. Vaccine Immunol. 2011; 18: 1850-1855
- TriTrypDB: a functional genomic resource for the Trypanosomatidae.Nucleic Acids Res. 2010; 38: D457-D462
- Assessing performance of orthology detection strategies applied to eukaryotic genomes.PLoS One. 2007; 2: e383
- Diagnostic peptide discovery: prioritization of pathogen diagnostic markers using multiple features.PLoS One. 2012; 7: e50748
- TcSNP: a database of genetic variation in Trypanosoma cruzi.Nucleic Acids Res. 2009; 37: D544-D549
- A genomic scale map of genetic diversity in Trypanosoma cruzi.BMC Genomics. 2012; 13: 736
- Genomic organization and expression profile of the mucin-associated surface protein (masp) family of the human pathogen Trypanosoma cruzi.Nucleic Acids Res. 2009; 37: 3407-3417
- The MASP family of Trypanosoma cruzi: changes in gene expression and antigenic profile during the acute phase of experimental infection.PLoS Negl. Trop. Dis. 2012; 6: e1779
- TcTASV: a novel protein family in Trypanosoma cruzi identified from a subtractive trypomastigote cDNA library.PLoS Negl Trop Dis. 2010; 4
- TcTASV-C, a protein family in Trypanosoma cruzi that is predominantly trypomastigote-stage specific and secreted to the medium.PLoS One. 2010; 8: e71192
- NNAlign: a web-based prediction method allowing non-expert end-user discovery of sequence motifs in quantitative peptide data.PLoS One. 2011; 6: e26781
- The outermost N-terminal region of tapasin facilitates folding of major histocompatibility complex class I.Eur. J. Immunol. 2009; 39: 2682-2694
- A comparison of normalization methods for high density oligonucleotide array data based on variance and bias.Bioinformatics. 2003; 19: 185-193
- ROCR: visualizing classifier performance in R.Bioinformatics. 2005; 21: 3940-3941
- Tracking repeats using significance and transitivity.Bioinformatics. 2004; 1: i311-i317
- Mapping Antigenic Motifs in the Trypomastigote Small Surface Antigen from Trypanosoma cruzi.Clin. Vaccine Immunol. 2015; 22: 304-312
- Structural analysis of B-cell epitopes in antibody:protein complexes.Mol. Immunol. 2013; 53: 24-34
- A Trypanosoma cruzi small surface molecule provides the first immunological evidence that Chagas' disease is due to a single parasite lineage.J. Exp. Med. 2002; 195: 401-413
- Immunological identification of Trypanosoma cruzi lineages in human infection along the endemic area.Am. J. Trop. Med. Hyg. 2011; 84: 78-84
- The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease.Science (80-.). 2005; 309: 409-415
- On silico peptide microarrays for high-resolution mapping of antibody epitopes and diverse protein-protein interactions.Nat. Med. 2012; 18: 1434-1440
- Immunosignature system for diagnosis of cancer.Proc. Natl. Acad. Sci. U.S.A. 2014; 111: E3072-E3080
- Scalable high-density peptide arrays for comprehensive health monitoring.Nat. Commun. 2014; 5: 4785
- Profiling the humoral immune response to infection by using proteome microarrays: high-throughput vaccine and diagnostic antigen discovery.Proc. Natl. Acad. Sci. U.S.A. 2005; 102: 547-552
- Proteomic Features Predict Seroreactivity against Leptospiral Antigens in Leptospirosis Patients.J. Proteome Res. 2015; 14: 549-556
- Systems biology approach predicts antibody signature associated with Brucella melitensis infection in humans.J. Proteome Res. 2011; 10: 4813-4824
- Improved method for predicting linear B-cell epitopes.Immunome Res. 2006; 2: 2
- Designing immunogenic peptides.Nat. Chem. Biol. 2013; 9: 749-753
- {T}he revised {T}rypanosoma cruzi subspecific nomenclature: rationale, epidemiological relevance and research applications.Infect. Genet. Evol. 2012; 12: 240-253
- High throughput selection of effective serodiagnostics for Trypanosoma cruzi infection.PLoS Negl. Trop. Dis. 2008; 2: e316
- Serodiagnosis of Echinococcus spp. infection: explorative selection of diagnostic antigens by peptide microarray.PLoS Negl. Trop. Dis. 2010; 4: e771
- High-throughput prediction of protein antigenicity using protein microarray data.Bioinformatics. 2010; 26: 2936-2943
Article info
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Footnotes
Author contributions: S.J.C. and F.A. designed research; S.J.C., C.S., V.B., C.A.B., and F.A. performed research; C.S. and J.A. contributed new reagents or analytic tools; S.J.C., M.N., J.M., V.T., A.C.F., O.C., C.A.B., and F.A. analyzed data; S.J.C., M.N., C.A.B., and F.A. wrote the paper.
DISCLOSURE DECLARATION. Claus Schafer-Nielsen is the owner and CEO of Schafer-N ApS. The other authors declare no conflict of interest.
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