Combinatory strategy using nanoscale proteomics and machine learning for T cell subtyping in peripheral blood of single multiple myeloma patients

Ye，Xueting1,2,3; Yang，Yun3,4; Zhou，Jihao1; Xu，Ling5,6; Wu，Long4; Huang，Peiwu3; Feng，Chun1; Ke，Peng1; He，An3; Li，Guoqiang1; Li，Yuan3; Li，Yangqiu5; Lam，Henry4; Zhang，Xinyou1; Tian，Ruijun3

2021-08-15

10.1016/j.aca.2021.338672

ANALYTICA CHIMICA ACTA   影响因子和分区

0003-2670

1873-4324

T cells play crucial roles in our immunity against hematological tumors by inducing sustained immune responses. Flow cytometry-based detection of a limited number of specific protein markers has been routinely applied for basic research and clinical investigation in this area. In this study, we combined flow cytometry with the simple integrated spintip-based proteomics technology (SISPROT) to characterize the proteome of primary T cell subtypes in the peripheral blood (PB) from single multiple myeloma (MM) patients. Taking advantage of the integrated high pH reversed-phase fractionation in the SISPROT device, the global proteomes of CD3, CD4 and CD8 T cells were firstly profiled with a depth of >7 000 protein groups for each cell type. The sensitivity of single-shot proteomic analysis was dramatically improved by optimizing the SISPROT and data-dependent acquisition parameters for nanogram-level samples. Eight subtypes of T cells were sorted from about 4 mL PB of single MM patients, and the individual subtype-specific proteomes with coverage among 1 702 and 3 699 protein groups were obtained from as low as 70 ng and up to 500 ng of cell lysates. In addition, we developed a two-step machine learning-based subtyping strategy for proof-of-concept classifying eight T cell subtypes, independent of their cell numbers and individual differences. Our strategy demonstrates an easy-to-use proteomic analysis on immune cells with the potential to discover novel subtype-specific protein biomarkers from limited clinical samples in future large scale clinical studies.

Label-free quantification Machine learning Multiple myeloma Nanoscale proteomics T cell subtypes

SCI ; EI

英语

第一 ; 通讯

WOS:000660288500002

20212310470784

Blood ; Clinical research ; Cytology ; Machine learning ; Molecular biology ; Nanotechnology ; Proteins

Biological Materials and Tissue Engineering:461.2 ; Biology:461.9 ; Immunology:461.9.1 ; Artificial Intelligence:723.4 ; Nanotechnology:761 ; Organic Compounds:804.1

CHEMISTRY

2-s2.0-85107269735

Scopus

1.Department of Hematology,The Second Clinical Medical College of Jinan University,The First Affiliated Hospital of Southern University of Science and Technology,Shenzhen People's Hospital,Shenzhen,518020,China
2.The First Affiliated Hospital,Jinan University,Guangzhou,510632,China
3.Department of Chemistry,Southern University of Science and Technology,Shenzhen,518055,China
4.Department of Chemical and Biological Engineering,The Hong Kong University of Science &Technology,Kowloon,Clear Water Bay,Hong Kong
5.Department of Hematology,First Affiliated Hospital; Institute of Hematology,School of Medicine; Key Laboratory for Regenerative Medicine of Ministry of Education,Jinan University,Guangzhou,510632,China
6.The Clinical Medicine Postdoctoral Research Station,Jinan University,Guangzhou,510632,China

Ye，Xueting,Yang，Yun,Zhou，Jihao,et al. Combinatory strategy using nanoscale proteomics and machine learning for T cell subtyping in peripheral blood of single multiple myeloma patients[J]. ANALYTICA CHIMICA ACTA,2021,1173.

Ye，Xueting.,Yang，Yun.,Zhou，Jihao.,Xu，Ling.,Wu，Long.,...&Tian，Ruijun.(2021).Combinatory strategy using nanoscale proteomics and machine learning for T cell subtyping in peripheral blood of single multiple myeloma patients.ANALYTICA CHIMICA ACTA,1173.

Ye，Xueting,et al."Combinatory strategy using nanoscale proteomics and machine learning for T cell subtyping in peripheral blood of single multiple myeloma patients".ANALYTICA CHIMICA ACTA 1173(2021).