An automated workflow based on data independent acquisition for practical and high-throughput personalized assay development and minimal residual disease monitoring in multiple myeloma patients

Author:

Wijnands Charissa1ORCID,Armony Gad2,Noori Somayya3,Gloerich Jolein2,Bonifay Vincent4,Caillon Hélène5,Luider Theo M.3,Brehmer Sven6,Pfennig Lennard6,Srikumar Tharan7,Trede Dennis6,Kruppa Gary8,Dejoie Thomas5,van Duijn Martijn M.3ORCID,van Gool Alain J.2,Jacobs Joannes F.M.1,Wessels Hans J.C.T.2

Affiliation:

1. Laboratory of Medical Immunology, Department of Laboratory Medicine , Radboud University Medical Center , Nijmegen , The Netherlands

2. Translational Metabolic Laboratory, Department of Human Genetics , Radboud University Medical Center , Nijmegen , The Netherlands

3. Department of Neurology , Erasmus MC, University Medical Center , Rotterdam , The Netherlands

4. Sebia , Lisses , France

5. Biochemistry Laboratory , Hospital of Nantes , Nantes , France

6. Bruker Daltonics GmbH , Bremen , Germany

7. Bruker Ltd , Milton , CA , USA

8. Bruker S.R.O. , Brno-City , Czech Republic

Abstract

Abstract Objectives Minimal residual disease (MRD) status in multiple myeloma (MM) is an important prognostic biomarker. Personalized blood-based targeted mass spectrometry detecting M-proteins (MS-MRD) was shown to provide a sensitive and minimally invasive alternative to MRD-assessment in bone marrow. However, MS-MRD still comprises of manual steps that hamper upscaling of MS-MRD testing. Here, we introduce a proof-of-concept for a novel workflow using data independent acquisition-parallel accumulation and serial fragmentation (dia-PASEF) and automated data processing. Methods Using automated data processing of dia-PASEF measurements, we developed a workflow that identified unique targets from MM patient sera and personalized protein sequence databases. We generated patient-specific libraries linked to dia-PASEF methods and subsequently quantitated and reported M-protein concentrations in MM patient follow-up samples. Assay performance of parallel reaction monitoring (prm)-PASEF and dia-PASEF workflows were compared and we tested mixing patient intake sera for multiplexed target selection. Results No significant differences were observed in lowest detectable concentration, linearity, and slope coefficient when comparing prm-PASEF and dia-PASEF measurements of serial dilutions of patient sera. To improve assay development times, we tested multiplexing patient intake sera for target selection which resulted in the selection of identical clonotypic peptides for both simplex and multiplex dia-PASEF. Furthermore, assay development times improved up to 25× when measuring multiplexed samples for peptide selection compared to simplex. Conclusions Dia-PASEF technology combined with automated data processing and multiplexed target selection facilitated the development of a faster MS-MRD workflow which benefits upscaling and is an important step towards the clinical implementation of MS-MRD.

Funder

KWF Kankerbestrijding

Health∼Holland

The Netherlands X-omics Initiative

Sebia

Publisher

Walter de Gruyter GmbH

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3