淀粉样变性
免疫球蛋白轻链
抗体
淀粉样变性
计算生物学
克隆(Java方法)
蛋白质基因组学
工作流程
亚型
生物
病理
基因
医学
免疫学
计算机科学
基因组
数据库
生物化学
基因组学
程序设计语言
作者
Surendra Dasari,Jason D. Theis,Julie A. Vrana,Oana M. Meureta,Patrick Quint,Prasuna Muppa,Roman M. Zenka,Renee C. Tschumper,Diane F. Jelinek,Jaime Davila,Vivekananda Sarangi,Paul J. Kurtin,Ahmet Doğan
标识
DOI:10.1021/acs.jproteome.5b00015
摘要
Immunoglobulin light chain (LC) amyloidosis (AL) is caused by deposition of clonal LCs produced by an underlying plasma cell neoplasm. The clonotypic LC sequences are unique to each patient, and they cannot be reliably detected by either immunoassays or standard proteomic workflows that target the constant regions of LCs. We addressed this issue by developing a novel sequence template-based workflow to detect LC variable (LCV) region peptides directly from AL amyloid deposits. The workflow was implemented in a CAP/CLIA compliant clinical laboratory dedicated to proteomic subtyping of amyloid deposits extracted from either formalin-fixed paraffin-embedded tissues or subcutaneous fat aspirates. We evaluated the performance of the workflow on a validation cohort of 30 AL patients, whose amyloidogenic clone was identified using a novel proteogenomics method, and 30 controls. The recall and negative predictive values of the workflow, when identifying the gene family of the AL clone, were 93 and 98%, respectively. Application of the workflow on a clinical cohort of 500 AL amyloidosis samples highlighted a bias in the LCV gene families used by the AL clones. We also detected similarity between AL clones deposited in multiple organs of systemic AL patients. In summary, AL proteomic data sets are rich in LCV region peptides of potential clinical significance that are recoverable with advanced bioinformatics.
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