A computational approach to matching multiple sclerosis-related, IGH CDR3s with a MBP epitope

IF 7 2区 医学 Q1 BIOLOGY
Justin M. Cole , Jacob T. Treanor , Cassondra M. Lyman , Diep Nguyen , Andrea Chobrutskiy , Boris I. Chobrutskiy , George Blanck
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引用次数: 0

Abstract

In multiple sclerosis (MS), T-cell receptors (TCRs) and antibodies specifically target the main structural proteins of myelin, including myelin basic protein (MBP), especially a specific, canonical, immunoglobulin (IG)-targeted MBP epitope. Efficient computational analyses to diagnose or monitor autoimmune conditions, which could have broad applicability in clinical trials or in diagnoses, remains a challenge. As such, we considered the possibility that focusing on the immunoglobin heavy chain (IGH) complementarity determining region-3 (CDR3) amino acid sequences could support the development of an efficient, convenient, and user-friendly approach to detecting or assessing IGH targets in MS. Thus, we applied a chemical complementarity scoring algorithm, extensively benchmarked in many cancer settings, to assess the combined electrostatic and hydrophobic attractiveness of large numbers of (individual patient) IGH CDR3s and the canonical IG MBP epitope. Samples and controls were filtered to only include CDR3s above a baseline chemical complementarity score. Then, the frequency of each unique IGH CDR3 (with the minimum MBP epitope complementarity) in the MS samples was compared to the same parameter for the control sample. Specifically, a greater number of high frequency IGH CDR3s, with chemically complementary to the canonical MBP epitope, was detected in 47 out of 48 MS-control comparisons, in most cases representing a p < 0.0001. With continued development, this approach has the potential to lead to a user-friendly computational screening tool for patients at risk for developing MS. Additional results indicate that the methodology could also be applied to antigen epitope discovery.
一种与MBP表位匹配多发性硬化症相关的IGH CDR3s的计算方法
在多发性硬化症(MS)中,t细胞受体(TCRs)和抗体特异性地靶向髓磷脂的主要结构蛋白,包括髓磷脂碱性蛋白(MBP),特别是特异性的、规范的、免疫球蛋白(IG)靶向的MBP表位。有效的计算分析来诊断或监测自身免疫性疾病,这可能在临床试验或诊断中具有广泛的适用性,仍然是一个挑战。因此,我们考虑了关注免疫球蛋白重链(IGH)互补性确定3区(CDR3)氨基酸序列的可能性,可以支持开发一种高效、方便、用户友好的方法来检测或评估ms中的IGH靶点。因此,我们应用了一种化学互补性评分算法,该算法在许多癌症环境中得到了广泛的基准测试。评估大量(个体患者)IGH CDR3s和典型IG MBP表位的静电和疏水联合吸引力。对样本和对照进行筛选,只包括高于基线化学互补性评分的CDR3s。然后,将MS样品中每个独特的IGH CDR3(具有最小MBP表位互补性)的频率与对照样品的相同参数进行比较。具体来说,在48个ms对照比较中,有47个检测到更多的高频IGH CDR3s,与典型MBP表位具有化学互补,在大多数情况下代表p
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来源期刊
Computers in biology and medicine
Computers in biology and medicine 工程技术-工程:生物医学
CiteScore
11.70
自引率
10.40%
发文量
1086
审稿时长
74 days
期刊介绍: Computers in Biology and Medicine is an international forum for sharing groundbreaking advancements in the use of computers in bioscience and medicine. This journal serves as a medium for communicating essential research, instruction, ideas, and information regarding the rapidly evolving field of computer applications in these domains. By encouraging the exchange of knowledge, we aim to facilitate progress and innovation in the utilization of computers in biology and medicine.
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