Bioinformatics tools for T-cell receptor based drugs

我们开发了一系列用于分析抗体序列和结构的软件和数据库。特别是，abYsis在网上得到广泛使用，并成功地销售给公司供内部使用。抗体已经显示出巨大程度的成功，因为新的治疗方法和相关的T细胞受体（TCR）现在正在被开发。我们希望重新利用我们已经开发的用于TCR的抗体的方法，以及开发新的方法和进行新的分析。将开发软件以将标准编号应用于TCR，从而可以分析序列和结构特征。将开发用于存储和分析公共序列和结构数据的工具，以便制作可用于开发TCR药物的软件。将分析晶体结构，以查看可用于改进TCR建模的域包装。然后将采用“大数据”方法分析巨大的下一代TCR序列数据集，存储序列数据，分析残基分布并添加注释，在每个步骤中对序列进行分类以减少不必要的分析。分类将包括筛选出非常不寻常的序列和那些可能具有免疫原性或可开发性问题的序列。将开发一个基本的网络界面，以便对数据进行探索，并对新的序列进行分析。

Aims and Objectives We have developed a range of software and databases for analysis of antibody sequence and structure. In particular, abYsis is widely used online and is successfully sold to companies for in-house use. Antibodies have shown a huge degree of success as novel therapeutics and the related T-Cell Receptors (TCRs) are now being exploited. We wish to repurpose methods we have developed for antibodies for use with TCRs as well as developing new approaches and performing new analyses. Software will be developed to apply standard numbering to TCRs, such that sequence and structure features can be analyzed. Tools will be developed to store and analyze public sequence and structure data with a view to producing software that can be used in the development of TCR-based drugs.Crystal structures will be analyzed to look at domain packing which can be exploited to improve TCR modelling. Huge nextgen TCR sequence datasets will then be analyzed taking a 'big data' approach storing sequence data, analyzing residue distributions and adding annotations, triaging sequences at each step to reduce unnecessary analysis. Triage will include screening out very unusual sequences and those with likely immunogenicity or developability issues. A basic web interface will be developed to allow the data to be explored and new sequences to be analyzed.