Multiplexed single cell protein expression analysis in solid tumours using a miniaturised microfluidic assay

Magness, Alastair; Squires, James; Griffiths, Beatrice; Khan, Khurum; Swain, Amanda; Willison, Keith R.; Cunningham, David; Gerlinger, Marco; Klug, David R.

doi:10.1088/2057-1739/aa6aae

Cited by 13 publications

(14 citation statements)

References 43 publications

(53 reference statements)

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“…For further understanding of cell and tissue heterogeneity, differentiation, diseases, and various biological processes involved in health and disease, it is necessary to study proteins at a single cell level. While various emerging technologies based on mass spectrometry are being developed in order to detect and quantify proteomes in single cells, [63][64][65][66][67] none of these currently have the resolution provided by IHC. By linking the identification of proteins with in situ location at tissue, cellular or subcellular level, important aspects of spatio-temporal expression are provided, since the location is tightly linked to a proteins' function.…”

Section: Discussionmentioning

confidence: 99%

The Human Protein Atlas—Spatial localization of the human proteome in health and disease

2020

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For a complete understanding of a system's processes and each protein's role in health and disease, it is essential to study protein expression with a spatial resolution, as the exact location of proteins at tissue, cellular, or subcellular levels is tightly linked to protein function. The Human Protein Atlas (HPA) project is a large-scale initiative aiming at mapping the entire human proteome using antibody-based proteomics and integration of various other omics technologies. The publicly available knowledge resource www.proteinatlas.org is one of the world's most visited biological databases and has been extensively updated during the last few years. The current version is divided into six main sections, each focusing on particular aspects of the human proteome: (a) the Tissue Atlas showing the distribution of proteins across all major tissues and organs in the human body; (b) the Cell Atlas showing the subcellular localization of proteins in single cells; (c) the Pathology Atlas showing the impact of protein levels on survival of patients with cancer; (d) the Blood Atlas showing the expression profiles of blood cells and actively secreted proteins; (e) the Brain Atlas showing the distribution of proteins in human, mouse, and pig brain; and (f) the Metabolic Atlas showing the involvement of proteins in human metabolism. The HPA constitutes an important resource for further understanding of human biology, and the publicly available datasets hold much promise for integration with other emerging efforts focusing on single cell analyses, both at transcriptomic and proteomic level.

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Section: Discussionmentioning

confidence: 99%

The Human Protein Atlas—Spatial localization of the human proteome in health and disease

2020

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“…Develop technologies that allow detection and quantification of proteomes in single cells to further understand cellular/tissue heterogeneity, differentiation, diseases and the intrinsic biological noise in health and disease 173,174 . Many single-cell proteomics advances will be explored to analyse cellular heterogeneity [175][176][177][178] . Sensitivity increases (analogous to PCR) and trade-offs maximizing coverage per cell with throughput/accuracy will be studied 179 .…”

Section: Apply and Improve Single-cell Proteomic Technologymentioning

confidence: 99%

A high-stringency blueprint of the human proteome

et al. 2020

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The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. On the occasion of the HPP’s tenth anniversary, we here report a 90.4% complete high-stringency human proteome blueprint. This knowledge is essential for discerning molecular processes in health and disease, as we demonstrate by highlighting potential roles the human proteome plays in our understanding, diagnosis and treatment of cancers, cardiovascular and infectious diseases.

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“…Different subpopulations of CRC cells from the same tumor analyzed by 2‐DE have been found to differ significantly in their biological properties that showed heterogeneity in posttranslational modifications of membrane, cytosol, and nuclear proteins . In addition, a single cell proteomic study performed by Magness and colleagues revealed p53 and phosphorylated p53 proteins showed variable expression between individual cancer cells obtained from the patient‐derived CRC xenografts by using a miniaturised microfluidic assay …”

Section: Intratumor Proteome Heterogeneitymentioning

confidence: 99%

Proteome Heterogeneity in Colorectal Cancer

Lim

2018

Proteomics

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Tumor heterogeneity is an important feature of colorectal cancer (CRC) manifested by dynamic changes in gene expression, protein expression, and availability of different tumor subtypes. Recent publications in the past 10 years have revealed proteome heterogeneity between different colorectal tumors and within the same tumor site. This paper reviews recent research works on the proteome heterogeneity in CRC, which includes the heterogeneity within a single tumor (intratumor heterogeneity), between different anatomical sites at the same organ, and between primary and metastatic sites (intertumor heterogeneity). The potential use of proteome heterogeneity in precision medicine and its implications in biomarker discovery and therapeutic outcomes will be discussed. Identification of the unique proteome landscape between and within individual tumors is imperative for understanding cancer biology and the management of CRC patients.

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Multiplexed single cell protein expression analysis in solid tumours using a miniaturised microfluidic assay

Cited by 13 publications

References 43 publications

The Human Protein Atlas—Spatial localization of the human proteome in health and disease

The Human Protein Atlas—Spatial localization of the human proteome in health and disease

A high-stringency blueprint of the human proteome

Proteome Heterogeneity in Colorectal Cancer

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