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The Human Melanoma Proteome Atlas-Complementing the melanoma transcriptome

Betancourt, Lazaro Hiram LU ; Gil, Jeovanis LU ; Sanchez, Aniel LU ; Kuras, Magdalena LU orcid ; Velasquez, Erika LU ; Kim, Yonghyo LU ; Sugihara, Yutaka LU ; Parada, Indira Pla LU orcid ; Appelqvist, Roger LU and Wieslander, Elisabet LU , et al. (2021) In Clinical and Translational Medicine 11(7). p.1-25
Abstract

The MM500 meta-study aims to establish a knowledge basis of the tumor proteome to serve as a complement to genome and transcriptome studies. Somatic mutations and their effect on the transcriptome have been extensively characterized in melanoma. However, the effects of these genetic changes on the proteomic landscape and the impact on cellular processes in melanoma remain poorly understood. In this study, the quantitative mass-spectrometry-based proteomic analysis is interfaced with pathological tumor characterization, and associated with clinical data. The melanoma proteome landscape, obtained by the analysis of 505 well-annotated melanoma tumor samples, is defined based on almost 16 000 proteins, including mutated proteoforms of... (More)

The MM500 meta-study aims to establish a knowledge basis of the tumor proteome to serve as a complement to genome and transcriptome studies. Somatic mutations and their effect on the transcriptome have been extensively characterized in melanoma. However, the effects of these genetic changes on the proteomic landscape and the impact on cellular processes in melanoma remain poorly understood. In this study, the quantitative mass-spectrometry-based proteomic analysis is interfaced with pathological tumor characterization, and associated with clinical data. The melanoma proteome landscape, obtained by the analysis of 505 well-annotated melanoma tumor samples, is defined based on almost 16 000 proteins, including mutated proteoforms of driver genes. More than 50 million MS/MS spectra were analyzed, resulting in approximately 13,6 million peptide spectrum matches (PSMs). Altogether 13 176 protein-coding genes, represented by 366 172 peptides, in addition to 52 000 phosphorylation sites, and 4 400 acetylation sites were successfully annotated. This data covers 65% and 74% of the predicted and identified human proteome, respectively. A high degree of correlation (Pearson, up to 0.54) with the melanoma transcriptome of the TCGA repository, with an overlap of 12 751 gene products, was found. Mapping of the expressed proteins with quantitation, spatiotemporal localization, mutations, splice isoforms, and PTM variants was proven not to be predicted by genome sequencing alone. The melanoma tumor molecular map was complemented by analysis of blood protein expression, including data on proteins regulated after immunotherapy. By adding these key proteomic pillars, the MM500 study expands the knowledge on melanoma disease.

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author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Antineoplastic Agents/therapeutic use, Blood Proteins/metabolism, Cell Line, Chromatography, High Pressure Liquid, Databases, Factual, Humans, Melanoma/drug therapy, Mutation, Protein Processing, Post-Translational/genetics, Proteome/metabolism, Proteomics/methods, Proto-Oncogene Proteins B-raf/genetics, Tandem Mass Spectrometry, Transcriptome
in
Clinical and Translational Medicine
volume
11
issue
7
article number
e451
pages
1 - 25
publisher
Wiley
external identifiers
  • pmid:34323402
ISSN
2001-1326
DOI
10.1002/ctm2.451
language
English
LU publication?
yes
additional info
© 2021 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.
id
ab922c65-205e-40a9-82c0-f4a9e6898735
date added to LUP
2022-03-23 13:12:43
date last changed
2023-02-25 02:44:25
@article{ab922c65-205e-40a9-82c0-f4a9e6898735,
  abstract     = {{<p>The MM500 meta-study aims to establish a knowledge basis of the tumor proteome to serve as a complement to genome and transcriptome studies. Somatic mutations and their effect on the transcriptome have been extensively characterized in melanoma. However, the effects of these genetic changes on the proteomic landscape and the impact on cellular processes in melanoma remain poorly understood. In this study, the quantitative mass-spectrometry-based proteomic analysis is interfaced with pathological tumor characterization, and associated with clinical data. The melanoma proteome landscape, obtained by the analysis of 505 well-annotated melanoma tumor samples, is defined based on almost 16 000 proteins, including mutated proteoforms of driver genes. More than 50 million MS/MS spectra were analyzed, resulting in approximately 13,6 million peptide spectrum matches (PSMs). Altogether 13 176 protein-coding genes, represented by 366 172 peptides, in addition to 52 000 phosphorylation sites, and 4 400 acetylation sites were successfully annotated. This data covers 65% and 74% of the predicted and identified human proteome, respectively. A high degree of correlation (Pearson, up to 0.54) with the melanoma transcriptome of the TCGA repository, with an overlap of 12 751 gene products, was found. Mapping of the expressed proteins with quantitation, spatiotemporal localization, mutations, splice isoforms, and PTM variants was proven not to be predicted by genome sequencing alone. The melanoma tumor molecular map was complemented by analysis of blood protein expression, including data on proteins regulated after immunotherapy. By adding these key proteomic pillars, the MM500 study expands the knowledge on melanoma disease.</p>}},
  author       = {{Betancourt, Lazaro Hiram and Gil, Jeovanis and Sanchez, Aniel and Kuras, Magdalena and Velasquez, Erika and Kim, Yonghyo and Sugihara, Yutaka and Parada, Indira Pla and Appelqvist, Roger and Wieslander, Elisabet and Welinder, Charlotte and de Almeida, Natália Pinto and Woldmar, Nicole and Marko-Varga, Matilda and Eriksson, Jonatan and Baldetorp, Bo and Ingvar, Christian and Olsson, Håkan and Lundgren, Lotta and Lindberg, Henrik and Oskolas, Henriett and Lee, Boram and Berge, Ethan and Sjögren, Marie and Eriksson, Carina and Kim, Dasol and Kwon, Ho Jeong and Rezeli, Melinda and Malm, Johan and Horvath, Peter and Horvatovich, Peter and Miliotis, Tasso and Ekedahl, Henrik and Marko-Varga, György}},
  issn         = {{2001-1326}},
  keywords     = {{Antineoplastic Agents/therapeutic use; Blood Proteins/metabolism; Cell Line; Chromatography, High Pressure Liquid; Databases, Factual; Humans; Melanoma/drug therapy; Mutation; Protein Processing, Post-Translational/genetics; Proteome/metabolism; Proteomics/methods; Proto-Oncogene Proteins B-raf/genetics; Tandem Mass Spectrometry; Transcriptome}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{1--25}},
  publisher    = {{Wiley}},
  series       = {{Clinical and Translational Medicine}},
  title        = {{The Human Melanoma Proteome Atlas-Complementing the melanoma transcriptome}},
  url          = {{http://dx.doi.org/10.1002/ctm2.451}},
  doi          = {{10.1002/ctm2.451}},
  volume       = {{11}},
  year         = {{2021}},
}