Open AccessThe Human Melanoma Proteome Atlas—Complementing the melanoma transcriptome
Author(s) -
Betancourt Lazaro Hiram,
Gil Jeovanis,
Sanchez Aniel,
Doma Viktória,
Kuras Magdalena,
Murillo Jimmy Rodriguez,
Velasquez Erika,
Çakır Uğur,
Kim Yonghyo,
Sugihara Yutaka,
Parada Indira Pla,
Szeitz Beáta,
Appelqvist Roger,
Wieslander Elisabet,
Welinder Charlotte,
Almeida Natália Pinto,
Woldmar Nicole,
MarkoVarga Matilda,
Eriksson Jonatan,
Pawłowski Krzysztof,
Baldetorp Bo,
Ingvar Christian,
Olsson Håkan,
Lundgren Lotta,
Lindberg Henrik,
Oskolas Henriett,
Lee Boram,
Berge Ethan,
Sjögren Marie,
Eriksson Carina,
Kim Dasol,
Kwon Ho Jeong,
Knudsen Beatrice,
Rezeli Melinda,
Malm Johan,
Hong Runyu,
Horvath Peter,
Szász A. Marcell,
Tímár József,
Kárpáti Sarolta,
Horvatovich Peter,
Miliotis Tasso,
Nishimura Toshihide,
Kato Harubumi,
Steinfelder Erik,
Oppermann Madalina,
Miller Ken,
Florindi Francesco,
Zhou Quimin,
Domont Gilberto B.,
Pizzatti Luciana,
Nogueira Fábio C. S.,
Szadai Leticia,
Németh István Balázs,
Ekedahl Henrik,
Fenyö David,
MarkoVarga György
Publication year - 2021
Publication title -
clinical and translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
H-Index - 1
ISSN - 2001-1326
DOI - 10.1002/ctm2.451
Subject(s) - proteome , transcriptome , melanoma , biology , human proteome project , computational biology , proteomics , gene , genome , human protein atlas , genetics , gene expression , protein expression
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.