cancers Article Mapping the Melanoma Plasma Proteome (MPP) Using Single-Shot Proteomics Interfaced with the WiMT Database Natália Almeida 1,2,3 , Jimmy Rodriguez 4 , Indira Pla Parada 5 , Yasset Perez-Riverol 6 , Nicole Woldmar 3,7 , Yonghyo Kim 8,9 , Henriett Oskolas 9 , Lazaro Betancourt 9 , Jeovanis Gil Valdés 9 , K. Barbara Sahlin 3,5 , Luciana Pizzatti 7 , A. Marcell Szasz 10 , Sarolta Kárpáti 11 , Roger Appelqvist 9 , Johan Malm 5 , Gilberto B. Domont 2 ,Fábio C. S. Nogueira 1,2, *, György Marko-Varga 3,12,13 and Aniel Sanchez 5, *   Citation: Almeida, N.; Rodriguez, J.; Pla Parada, I.; Perez-Riverol, Y.; Woldmar, N.; Kim, Y.; Oskolas, H.; Betancourt, L.; Valdés, J.G.; Sahlin, K.B.; et al. Mapping the Melanoma Plasma Proteome (MPP) Using Single-Shot Proteomics Interfaced with the WiMT Database. Cancers 2021, 13, 6224. https:// doi.org/10.3390/cancers13246224 Academic Editors: Jeffrey A. Borgia and Samir M. Hanash Received: 4 October 2021 Accepted: 8 December 2021 Published: 10 December 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Laboratory of Proteomics/LADETEC, Universidade Federal Do Rio de Janeiro, Rio de Janeiro 21941-598, Brazil; nataliapalmeida@pos.iq.ufrj.br 2 Proteomics Unit, Institute of Chemistry, Universidade Federal Do Rio de Janeiro, Rio de Janeiro 21941-909, Brazil; gilberto@iq.ufrj.br 3 Clinical Protein Science & Imaging, Biomedical Center, Department of Biomedical Engineering, Lund University, BMC D13, 22184 Lund, Sweden; nicole.woldmar@pos.iq.ufrj.br (N.W.); barbara.sahlin@med.lu.se (K.B.S.); gyorgy.marko-varga@bme.lth.se (G.M.-V.) 4 Division of Chemistry I, Department of Biochemistry and Biophysics, Karolinska Institute, 17165 Stockholm, Sweden; jimmy.esneider.rodriguez@ki.se 5 Section for Clinical Chemistry, Department of Translational Medicine, Lund University, Skåne University Hospital Malmö, 20502 Malmö, Sweden; indira.pla_parada@med.lu.se (I.P.P.); johan.malm@med.lu.se (J.M.) 6 European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK; yperez@ebi.ac.uk 7 Laboratory of Molecular Biology and Blood Proteomics—LADETEC, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro 21941-598, Brazil; pizzatti@iq.ufrj.br 8 Data Convergence Drug Research Center, Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology (KRICT), Daejeon 34114, Korea; yonghyo@krict.re.kr 9 Division of Oncology, Department of Clinical Sciences Lund, Lund University, 22185 Lund, Sweden; henriett.kovacsne_oskolas@med.lu.se (H.O.); lazaro_hiram.betancourt_nunez@med.lu.se (L.B.); jeovanis.gil_valdes@med.lu.se (J.G.V.); roger.appelqvist@bme.lth.se (R.A.) 10 Oncology Center, Semmelweis University, 1083 Budapest, Hungary; szasz.attila_marcell@med.semmelweis-univ.hu 11 Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, 1085 Budapest, Hungary; karpati.sarolta@medsemmelweis-univ.hu 12 Chemical Genomics Global Research Lab, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722,Korea 13 Department of Surgery, Tokyo Medical University, 6-7-1 Nishishinjiku Shinjiku-ku, Tokyo 160-0023, Japan * Correspondence: fabiocsn@iq.ufrj.br (F.C.S.N.); aniel.sanchez@med.lu.se (A.S.) Simple Summary: We developed a clinical proteomics methodology, known as Wise MS Transfer (WiMT), for deep identification of blood proteins in undepleted plasma samples. We applied it to the analysis of undepleted melanoma plasma samples as a proof of principle. Malignant melanoma is the most aggressive type of skin cancer, and early diagnostic and prognostic predictors are essential to establish the most suitable treatment tailored to the patient. Our results showed the greatest identification of proteins and biological processes to date reported for a “dilute and shoot” approach within plasma samples from melanoma patients. More than 1200 proteins related to key biological processes in melanoma progression were mapped, including signaling (the PI3K–Akt signaling pathway), immune system processes (complement and coagulation cascade), and secretion (exosome proteins). These proteins and related biological processes constitute the core of blood components that could be monitored by mass spectrometry in clinical proteomic studies from undepleted plasma samples in melanoma. Abstract: Plasma analysis by mass spectrometry-based proteomics remains a challenge due to its large dynamic range of 10 orders in magnitude. We created a methodology for protein identification known as Wise MS Transfer (WiMT). Melanoma plasma samples from biobank archives were directly analyzed using simple sample preparation. WiMT is based on MS1 features between several MS runs Cancers 2021, 13, 6224. https://doi.org/10.3390/cancers13246224 https://www.mdpi.com/journal/cancers