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Abstract The MM500 study is an initiative to map the protein levels in malignant melanoma tumor samples, focused on in‐depth histopathology coupled to proteome characterization. The protein levels and localization were determined for a broad spectrum of diverse, surgically isolated melanoma tumors originating from multiple body locations. More than 15,500 proteoforms were identified by mass spectrometry, from which chromosomal and subcellular localization was annotated within both primary and metastatic melanoma. The data generated by global proteomic experiments covered 72% of the proteins identified in the recently reported high stringency blueprint of the human proteome. This study contributes to the NIH Cancer Moonshot initiative combining detailed histopathological presentation with the molecular characterization for 505 melanoma tumor samples, localized in 26 organs from 232 patients.

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.

Abstract BackgroundIn the postgenomic era, it has become evident that analysis of genetic and protein expression changes alone is not sufficient to understand most disease processes in e.g. cardiovascular and cancer disease. Biobanking has been identified as an important area for development and discovery of better diagnostic tools and new treatment modalities. Biobanks are developed in order to integrate the collection of clinical samples from both healthy individuals and patients and provide valuable information that will make possible improved patient care. Modern healthcare developments are intimately linked to information based on studies of patient samples from biobank archives in large scale studies. Today biobanks form important national, as well as international, networks that share and combine global resources. MethodsWe have developed and validated a novel biobanking workflow process that utilizes 384‐tube systems with a high speed sample array robot with unique processing principles. ResultsThe 384‐tube format and robotic processing is incorporated into a cancer and cardiovascular diagnostic/prognostic research program with therapeutic interventions. Our biobank practice has gained acceptance within many hospitals and research units and is based on high‐density sample storage with small aliquot sample volumes. The previous standard of 5–10 mL sample volume tubes is being replaced by smaller volumes of 50–70 μL blood fractions that typically result in hundreds of thousands of aliquot fractions in 384‐tube systems. ConclusionsOur novel biobanking workflow process is robust and well suited for clinical studies.