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Chimeric peptide constructs comprising linear B-cell epitopes: application to the serodiagnosis of infectious diseases.

Lu Y, Li Z, Teng H, Xu H, Qi S, He J, Gu D, Chen Q, Ma H - Sci Rep (2015)

Bottom Line: However, the long-predicted diagnostic value of epitopes has not been realized.Using DEIFS for malaria, we identified 6 epitopes from 8 peptides and combined them into 3 chimeric peptide constructs.In addition to applications in diagnosis, DEIFS could also be used in the diagnosis of virus and bacterium infections, discovery of vaccine candidates, evaluation of vaccine potency, and study of disease progression.

View Article: PubMed Central - PubMed

Affiliation: Nano-Bio-Chem Centre, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, P. R. China.

ABSTRACT
Linear B-cell epitopes are ideal biomarkers for the serodiagnosis of infectious diseases. However, the long-predicted diagnostic value of epitopes has not been realized. Here, we demonstrated a method, diagnostic epitopes in four steps (DEIFS), that delivers a combination of epitopes for the serodiagnosis of infectious diseases with a high success rate. Using DEIFS for malaria, we identified 6 epitopes from 8 peptides and combined them into 3 chimeric peptide constructs. Along with 4 other peptides, we developed a rapid diagnostic test (RDT), which is able to differentiate Plasmodium falciparum (P. falciparum) from Plasmodium vivax (P. vivax) infections with 95.6% overall sensitivity and 99.1% overall specificity. In addition to applications in diagnosis, DEIFS could also be used in the diagnosis of virus and bacterium infections, discovery of vaccine candidates, evaluation of vaccine potency, and study of disease progression.

No MeSH data available.


Related in: MedlinePlus

Binarization/digitalization strategy and RDT validation (a) Under the single index mode with intensity-cutoff at SNR = 2.3, P34-88 had a 73.2% sensitivity and 98.4% specificity. The inserted figure gives an overlapped view of two curves (b). Under binarization/digitalization and setting the binary-cutoff (SNR) and digit-cutoff (n) both at 2, the 8-peptide resulted in 92.7% sensitivity and 99.2% specificity. (c) Correlation of 28 two-peptide combinations for the P. falciparum infected training group. The Exp. value was the number obtained from experiments. For digit-cutoff n = 1, the Cal. value was the same as the Exp. value: these open dots are located on the diagonal line. For n = 2, the Cal. value (the solid red dots indicated by the filled black arrow) is the product of any two Exp. values (the open red dots indicated by the two open black arrows). (d) Correlation of 56 three-peptide combinations for the training group. For n = 3, the Cal. value (the solid purple dots) is the product of any three Exp. values. (e) For RDT (a 3 × 3 array layout): positive control, negative control and 7 other peptides were arrayed as Region I and II. (f) Any two of the five dots in Region II showing positive results indicated malaria infection; otherwise, the indication was negative for malaria. For malaria infected serum, two dots in Region I indicated positive Pv. infection. No dots indicated P. falciparum infection. A single dot could not be certainly interpreted, and a third party test is required.
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f5: Binarization/digitalization strategy and RDT validation (a) Under the single index mode with intensity-cutoff at SNR = 2.3, P34-88 had a 73.2% sensitivity and 98.4% specificity. The inserted figure gives an overlapped view of two curves (b). Under binarization/digitalization and setting the binary-cutoff (SNR) and digit-cutoff (n) both at 2, the 8-peptide resulted in 92.7% sensitivity and 99.2% specificity. (c) Correlation of 28 two-peptide combinations for the P. falciparum infected training group. The Exp. value was the number obtained from experiments. For digit-cutoff n = 1, the Cal. value was the same as the Exp. value: these open dots are located on the diagonal line. For n = 2, the Cal. value (the solid red dots indicated by the filled black arrow) is the product of any two Exp. values (the open red dots indicated by the two open black arrows). (d) Correlation of 56 three-peptide combinations for the training group. For n = 3, the Cal. value (the solid purple dots) is the product of any three Exp. values. (e) For RDT (a 3 × 3 array layout): positive control, negative control and 7 other peptides were arrayed as Region I and II. (f) Any two of the five dots in Region II showing positive results indicated malaria infection; otherwise, the indication was negative for malaria. For malaria infected serum, two dots in Region I indicated positive Pv. infection. No dots indicated P. falciparum infection. A single dot could not be certainly interpreted, and a third party test is required.

Mentions: Second, we further assign:, where Dsum is a variable similar to the role of SNR and n is the digit-cutoff value for the digitized diagnostic microarray. For example, if the digit-cutoff n = 2, Dsum = 0 and 1 indicate healthy (i.e., negative for P. falciparum-specific antibodies), and Dsum ≥ 2 indicates P. falciparum infection (i.e., positive for P. falciparum-specific antibodies). A surprising improvement was observed when we set the digit-cutoff to n = 2; both the sensitivity and specificity increased from below 73.2% to 92.7% and from 98.4% to 99.2%, respectively (Fig. 5a,b).


Chimeric peptide constructs comprising linear B-cell epitopes: application to the serodiagnosis of infectious diseases.

Lu Y, Li Z, Teng H, Xu H, Qi S, He J, Gu D, Chen Q, Ma H - Sci Rep (2015)

Binarization/digitalization strategy and RDT validation (a) Under the single index mode with intensity-cutoff at SNR = 2.3, P34-88 had a 73.2% sensitivity and 98.4% specificity. The inserted figure gives an overlapped view of two curves (b). Under binarization/digitalization and setting the binary-cutoff (SNR) and digit-cutoff (n) both at 2, the 8-peptide resulted in 92.7% sensitivity and 99.2% specificity. (c) Correlation of 28 two-peptide combinations for the P. falciparum infected training group. The Exp. value was the number obtained from experiments. For digit-cutoff n = 1, the Cal. value was the same as the Exp. value: these open dots are located on the diagonal line. For n = 2, the Cal. value (the solid red dots indicated by the filled black arrow) is the product of any two Exp. values (the open red dots indicated by the two open black arrows). (d) Correlation of 56 three-peptide combinations for the training group. For n = 3, the Cal. value (the solid purple dots) is the product of any three Exp. values. (e) For RDT (a 3 × 3 array layout): positive control, negative control and 7 other peptides were arrayed as Region I and II. (f) Any two of the five dots in Region II showing positive results indicated malaria infection; otherwise, the indication was negative for malaria. For malaria infected serum, two dots in Region I indicated positive Pv. infection. No dots indicated P. falciparum infection. A single dot could not be certainly interpreted, and a third party test is required.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4543967&req=5

f5: Binarization/digitalization strategy and RDT validation (a) Under the single index mode with intensity-cutoff at SNR = 2.3, P34-88 had a 73.2% sensitivity and 98.4% specificity. The inserted figure gives an overlapped view of two curves (b). Under binarization/digitalization and setting the binary-cutoff (SNR) and digit-cutoff (n) both at 2, the 8-peptide resulted in 92.7% sensitivity and 99.2% specificity. (c) Correlation of 28 two-peptide combinations for the P. falciparum infected training group. The Exp. value was the number obtained from experiments. For digit-cutoff n = 1, the Cal. value was the same as the Exp. value: these open dots are located on the diagonal line. For n = 2, the Cal. value (the solid red dots indicated by the filled black arrow) is the product of any two Exp. values (the open red dots indicated by the two open black arrows). (d) Correlation of 56 three-peptide combinations for the training group. For n = 3, the Cal. value (the solid purple dots) is the product of any three Exp. values. (e) For RDT (a 3 × 3 array layout): positive control, negative control and 7 other peptides were arrayed as Region I and II. (f) Any two of the five dots in Region II showing positive results indicated malaria infection; otherwise, the indication was negative for malaria. For malaria infected serum, two dots in Region I indicated positive Pv. infection. No dots indicated P. falciparum infection. A single dot could not be certainly interpreted, and a third party test is required.
Mentions: Second, we further assign:, where Dsum is a variable similar to the role of SNR and n is the digit-cutoff value for the digitized diagnostic microarray. For example, if the digit-cutoff n = 2, Dsum = 0 and 1 indicate healthy (i.e., negative for P. falciparum-specific antibodies), and Dsum ≥ 2 indicates P. falciparum infection (i.e., positive for P. falciparum-specific antibodies). A surprising improvement was observed when we set the digit-cutoff to n = 2; both the sensitivity and specificity increased from below 73.2% to 92.7% and from 98.4% to 99.2%, respectively (Fig. 5a,b).

Bottom Line: However, the long-predicted diagnostic value of epitopes has not been realized.Using DEIFS for malaria, we identified 6 epitopes from 8 peptides and combined them into 3 chimeric peptide constructs.In addition to applications in diagnosis, DEIFS could also be used in the diagnosis of virus and bacterium infections, discovery of vaccine candidates, evaluation of vaccine potency, and study of disease progression.

View Article: PubMed Central - PubMed

Affiliation: Nano-Bio-Chem Centre, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, P. R. China.

ABSTRACT
Linear B-cell epitopes are ideal biomarkers for the serodiagnosis of infectious diseases. However, the long-predicted diagnostic value of epitopes has not been realized. Here, we demonstrated a method, diagnostic epitopes in four steps (DEIFS), that delivers a combination of epitopes for the serodiagnosis of infectious diseases with a high success rate. Using DEIFS for malaria, we identified 6 epitopes from 8 peptides and combined them into 3 chimeric peptide constructs. Along with 4 other peptides, we developed a rapid diagnostic test (RDT), which is able to differentiate Plasmodium falciparum (P. falciparum) from Plasmodium vivax (P. vivax) infections with 95.6% overall sensitivity and 99.1% overall specificity. In addition to applications in diagnosis, DEIFS could also be used in the diagnosis of virus and bacterium infections, discovery of vaccine candidates, evaluation of vaccine potency, and study of disease progression.

No MeSH data available.


Related in: MedlinePlus