Valens: A Mass Spectrometry-Based Antibody Sequencing Tool by Digital Proteomics

描述(由申请人提供)：单抗对目标分子表现出高度的特异性，因此已被成功地用作治疗和诊断试剂。组成抗体一级结构的氨基酸序列在很大程度上决定了抗体的结合偏好和效力。因此，抗体测序是开发新的抗体疗法的核心要求。我们提出了一种直接从蛋白质序列进行抗体测序的方法，不需要源细胞，这使得它在许多实验室和临床环境中都是实用的。此外，我们建议的计算方法是完全自动化的，通过将测序所需的时间从几周减少到几个小时，将增加吞吐量。我们计划在可以在一台台式计算机上运行的独立工具中实现我们的方法，或者利用云计算中可用的大量资源。我们还将为没有质谱仪设备或计算资源的用户提供内部测序服务。 与公共卫生相关：确定抗体序列的特征是开发基于抗体的治疗和诊断方法的先决条件，这些方法在药物市场中占越来越大的份额。我们提出了一种新的基于质谱学的抗体测序计算方法，该方法将极大地提高抗体表征的速度，并缩短从实验室开发到临床治疗的时间。

DESCRIPTION (provided by applicant): Monoclonal antibodies exhibit high specificity for target molecules and for that reason have been successfully utilized as therapeutic and diagnostic agents. The sequence of amino acids comprising the primary structure of an antibody is largely responsible for its binding preference and efficacy. Therefore, antibody sequencing is a central requirement for the development of novel antibody therapies. We propose a method of performing antibody sequencing directly from the protein sequence, without requiring the source cell, which makes it practical for many lab and clinical settings. In addition, our proposed computational method is fully automated, and will increase throughput by dramatically reducing the time required for sequencing from weeks to hours. We plan to implement our method in both a stand-alone tool that may be run on a single desktop computer, or make use of the vast resources available in cloud computing. We will also provide an in-house sequencing service for users without access to the mass spectrometry equipment or computing resources. PUBLIC HEALTH RELEVANCE: Characterizing the sequence of an antibody is a prerequisite for the development of antibody based therapies and diagnostic methods, which represent a growing segment of the drug market. We propose a novel computational method of antibody sequencing based on mass spectrometry, which will dramatically increase the rate of antibody characterization, and reduce the time from development in the lab to treatment in the clinic.