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利用计算机免疫信息学工具和肽微阵列技术鉴定具有诊断潜力的埃及血吸虫和曼氏血吸虫线性 B 细胞表位。

Identification of Schistosoma haematobium and Schistosoma mansoni linear B-cell epitopes with diagnostic potential using in silico immunoinformatic tools and peptide microarray technology.

机构信息

Department of Biochemistry, Faculty of Medicine and Health Sciences, Midlands State University, Senga Road, Gweru, Zimbabwe.

Department of Biotechnology and Biochemistry, Faculty of Science, University of Zimbabwe, Mount Pleasant, Harare, Zimbabwe.

出版信息

PLoS Negl Trop Dis. 2024 Aug 22;18(8):e0011887. doi: 10.1371/journal.pntd.0011887. eCollection 2024 Aug.

Abstract

INTRODUCTION

Immunoinformatic tools can be used to predict schistosome-specific B-cell epitopes with little sequence identity to human proteins and antigens other than the target. This study reports an approach for identifying schistosome peptides mimicking linear B-cell epitopes using in-silico tools and peptide microarray immunoassay validation.

METHOD

Firstly, a comprehensive literature search was conducted to obtain published schistosome-specific peptides and recombinant proteins with the best overall diagnostic performances. For novel peptides, linear B-cell epitopes were predicted from target recombinant proteins using ABCpred, Bcepred and BepiPred 2.0 in-silico tools. Together with the published peptides, predicted peptides with the highest probability of being B-cell epitopes and the lowest sequence identity with proteins from human and other pathogens were selected. Antibodies against the peptides were measured in sera, using peptide microarray immunoassays. Area under the ROC curve was calculated to assess the overall diagnostic performances of the peptides.

RESULTS

Peptide AA81008-19-30 had excellent and acceptable diagnostic performances for discriminating S. mansoni and S. haematobium positives from healthy controls, with AUC values of 0.8043 and 0.7326 respectively for IgG. Peptides MS3_10186-123-131, MS3_10385-339-354, SmSPI-177-193, SmSPI-379-388, MS3-10186-40-49 and SmS-197-214 had acceptable diagnostic performances for discriminating S. mansoni positives from healthy controls with AUC values ranging from 0.7098 to 0.7763 for IgG. Peptides SmSPI-359-372, Smp126160-438-452 and MS3 10186-25-41 had acceptable diagnostic performances for discriminating S. mansoni positives from S. mansoni negatives with AUC values of 0.7124, 0.7156 and 0.7115 respectively for IgG. Peptide MS3-10186-40-49 had an acceptable diagnostic performance for discriminating S. mansoni positives from healthy controls, with an AUC value of 0.7413 for IgM.

CONCLUSION

One peptide with a good diagnostic performance and nine peptides with acceptable diagnostic performances were identified using the immunoinformatic approach and peptide microarray validation. There is need for evaluation of the peptides with true negatives and a good standard positive reference.

摘要

简介

免疫信息学工具可用于预测与目标以外的人类蛋白和抗原仅有微小序列同源性的血吸虫特异性 B 细胞表位。本研究报告了一种使用计算机模拟工具和肽微阵列免疫分析验证来识别模拟线性 B 细胞表位的血吸虫肽的方法。

方法

首先,通过全面的文献检索,获得具有最佳总体诊断性能的已发表的血吸虫特异性肽和重组蛋白。对于新的肽,使用 ABCpred、Bcepred 和 BepiPred 2.0 计算机模拟工具,从目标重组蛋白中预测线性 B 细胞表位。与已发表的肽一起,选择具有最高 B 细胞表位概率和与人类及其他病原体蛋白最低序列同源性的预测肽。使用肽微阵列免疫分析测量针对这些肽的抗体。计算 ROC 曲线下面积以评估肽的总体诊断性能。

结果

肽 AA81008-19-30 对区分曼氏血吸虫和埃及血吸虫阳性与健康对照具有极好和可接受的诊断性能,其 IgG 的 AUC 值分别为 0.8043 和 0.7326。肽 MS3_10186-123-131、MS3_10385-339-354、SmSPI-177-193、SmSPI-379-388、MS3_10186-40-49 和 SmS-197-214 对区分曼氏血吸虫阳性与健康对照具有可接受的诊断性能,其 IgG 的 AUC 值范围为 0.7098 至 0.7763。肽 SmSPI-359-372、Smp126160-438-452 和 MS3 10186-25-41 对区分曼氏血吸虫阳性与曼氏血吸虫阴性具有可接受的诊断性能,其 IgG 的 AUC 值分别为 0.7124、0.7156 和 0.7115。肽 MS3-10186-40-49 对区分曼氏血吸虫阳性与健康对照具有可接受的诊断性能,其 AUC 值为 0.7413。

结论

通过免疫信息学方法和肽微阵列验证,鉴定出一种具有良好诊断性能的肽和 9 种具有可接受诊断性能的肽。需要评估具有真正阴性和良好标准阳性参考的肽。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f8/11373837/fe57ad5a7545/pntd.0011887.g001.jpg

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