4.9.1 Protein normalization
The results from protein identification and quantifica-tion were imported into Perseus software.113 Data were
normalized by log2 transforming the protein intensities, and standardization was performed by subtracting indi-vidual values by the median in each sample. The proteins showing less variability across all batches that were identi-fied in 100% of the samples were used to correct the abun-dance differences between batches. To do that, individ-ual protein intensities in each batch were subtracted by the median abundance of selected proteins in the specific batch. After correction, the median abundance for each protein across all samples was calculated and reported as the relative abundance in our melanoma proteome.
4.9.2 Stoichiometry of acetylated lysines
The lysine acetylation stoichiometry identification and quantification were estimated as previously described.80,81 Briefly, raw files were analyzed with Pview software to identify and calculate the site-specific acetylation occu-pancy. Also, only those peptides identified in both, Pview and Proteome Discoverer were considered for reporting their acetylation stoichiometry.
4.9.3 Kinase-specific phosphorylation site prediction
Phosphopeptides sequences were edited to include “#” in front of the S, T, or Y phosphorylation sites. The back-ground database consisted of a fasta file from all iden-tified phosphorylated proteins in this study. The soft-ware motifeR112 was used to align the phosphopeptide sequences with the background database, providing a uni-form sequence length of 15 amino acids. The motifeR was also used to enrich phosphorylation motifs and retrieve kinase-substrate annotation. All kinases identified in the MM500 proteome and kinases predicted by the enriched motifs were visualized in the context of the human kinome superfamily using Coral.78
D A T A A N D C O D E AVA I L A B I L I T Y
The data that support the findings of this study are openly available in ProteomeXchange at http://www.
proteomexchange.org/, reference numbers PXD001725, PXD001724, PXD009630, PXD017968, and PXD026086 and will be complemented by the addition of more data from the study. The TCGA data was downloaded from cBioPortal https://www.cbioportal.org. The code for MM500 study can be found at https://github.
com/rhong3/TCGA_melanoma. Table S1 of Support-ing Information is available at https://github.com/
rhong3/TCGA_melanoma/tree/master/Supporting%
20Information%20tables.
A C K N O W L E D G M E N T S
This study was supported by grants from the Berta Kam-prad Foundation, the Mats and Stefan Paulsson Trust, Lund, Sweden, and the National Research Foundation of Korea (MSIP; 2015K1A1A2028365). We would like to thank Thermo Fisher Scientific for their generous support and Liconic UK, for Biobanking support. This work was done under the auspices of a Memorandum of Understanding between the European Cancer Moonshot Center in Lund and the U.S. National Cancer Institute’s International Can-cer Proteogenome Consortium (ICPC). ICPC encourages international cooperation among institutions and nations in proteogenomic cancer research in which proteogenomic datasets are made available to the public. This work was also done in collaboration with the U.S. National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC). The study was also conducted under the Mem-orandum of Understanding between the Federal Univer-sity of Rio de Janeiro, Brazil (grants CAPES 88887.130697, CNPq 440613/2016-7 and 308341-2019-8, and FAPERJ E-26/210.173/2018 to G.B.), and Lund University, Sweden. We thank the Brazilian foundation CAPES for the scholarship to N.W and acknowledge the support to I.B.N by the Hun-garian Academy of Sciences (OTKA-NKFI, K-125509).
O R C I D Fábio C. S. Nogueira https://orcid.org/0000-0001-5507-7142
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S U P P O R T I N G I N F O R M A T I O N
Additional supporting information may be found online in the Supporting Information section at the end of the article.
How to cite this article: Betancourt LH, Gil J, Sanchez A, et al. The Human Melanoma Proteome Atlas—Complementing the melanoma
transcriptome.Clin Transl Med. 2021;11:e451.
https://doi.org/10.1002/ctm2.451