The Human Melanoma Proteome Atlas—Complementing the melanoma transcriptome

Autor: Lazaro Hiram Betancourt, Jeovanis Gil, Aniel Sanchez, Viktória Doma, Magdalena Kuras, Jimmy Rodriguez Murillo, Erika Velasquez, Uğur Çakır, Yonghyo Kim, Yutaka Sugihara, Indira Pla Parada, Beáta Szeitz, Roger Appelqvist, Elisabet Wieslander, Charlotte Welinder, Natália Pinto deAlmeida, Nicole Woldmar, Matilda Marko‐Varga, Jonatan Eriksson, Krzysztof Pawłowski, Bo Baldetorp, Christian Ingvar, Håkan Olsson, Lotta Lundgren, Henrik Lindberg, Henriett Oskolas, Boram Lee, Ethan Berge, Marie Sjögren, Carina Eriksson, Dasol Kim, Ho Jeong Kwon, Beatrice Knudsen, Melinda Rezeli, Johan Malm, Runyu Hong, Peter Horvath, A. Marcell Szász, József Tímár, Sarolta Kárpáti, Peter Horvatovich, Tasso Miliotis, Toshihide Nishimura, Harubumi Kato, Erik Steinfelder, Madalina Oppermann, Ken Miller, Francesco Florindi, Quimin Zhou, Gilberto B. Domont, Luciana Pizzatti, Fábio C. S. Nogueira, Leticia Szadai, István Balázs Németh, Henrik Ekedahl, David Fenyö, György Marko‐Varga
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Clinical and Translational Medicine, Vol 11, Iss 7, Pp n/a-n/a (2021)
Druh dokumentu: article
ISSN: 2001-1326
DOI: 10.1002/ctm2.451
Popis: 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 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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