Dataset Information

Novel Functional Proteins Coded by the Human Genome Discovered in Metastases of Melanoma Patients

ABSTRACT: In the advanced stages, malignant melanoma (MM) has a very poor prognosis. Due to tremendous efforts in cancer research, the overall survival of metastatic melanoma has doubled; however, complete eradication of the disease is almost unknown. With the advent of proteomics, deep-mining studies can reach low-abundant expression areas. The complexity of the proteome, however, still surpasses the dynamic range capabilities of current analytical techniques. Consequently, many predicted protein products with potential biological functions have not yet been verified in experimental proteomic data. This category of ‘missing proteins’ (MP) is comprised of all proteins that have been predicted but are currently unverified. As part of the initiative launched in 2016 in the United States, the European Cancer Moonshot Center has performed numerous deep proteomics analyses on samples from MM patients. In this study, nine MPs were clearly identified by mass spectrometry in MM metastases. Some MPs significantly-correlated with proteins that possess identical PFAM structural domains; and other MPs were significantly-associated with cancer-related proteins. This is the first study to our knowledge, where unknown and novel proteins have been annotated within metastasis, from Melanoma Cancer patients.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lymph Node

DISEASE(S): Melanoma

SUBMITTER: Aniel Sanchez

LAB HEAD: Gyorgy Marko-varga

PROVIDER: PXD017968 | Pride | 2020-03-11

REPOSITORIES: Pride

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			Action	DRS
	20181010_MM_TMT_AllBatches_Isoforms_100_IntThreshold_A0A0J9Y_V2.mzML	Mzml
	20181010_MM_TMT_AllBatches_Isoforms_100_IntThreshold_A0A0J9Y_V2.pride.mgf.gz	Mgf
	20181010_MM_TMT_AllBatches_Isoforms_100_IntThreshold_C9JJ37_V2.mzML	Mzml
	20181010_MM_TMT_AllBatches_Isoforms_100_IntThreshold_C9JJ37_V2.pride.mgf.gz	Mgf
	20181010_MM_TMT_AllBatches_Isoforms_100_IntThreshold_Q32M45.mzML	Mzml

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Publications

Novel functional proteins coded by the human genome discovered in metastases of melanoma patients.

Sanchez Aniel A Kuras Magdalena M Murillo Jimmy Rodriguez JR Pla Indira I Pawlowski Krzysztof K Szasz A Marcell AM Gil Jeovanis J Nogueira Fábio C S FCS Perez-Riverol Yasset Y Eriksson Jonatan J Appelqvist Roger R Miliotis Tasso T Kim Yonghyo Y Baldetorp Bo B Ingvar Christian C Olsson Håkan H Lundgren Lotta L Ekedahl Henrik H Horvatovich Peter P Sugihara Yutaka Y Welinder Charlotte C Wieslander Elisabet E Kwon Ho Jeong HJ Domont Gilberto B GB Malm Johan J Rezeli Melinda M Betancourt Lazaro Hiram LH Marko-Varga György G

Cell biology and toxicology 20191010 3

In the advanced stages, malignant melanoma (MM) has a very poor prognosis. Due to tremendous efforts in cancer research over the last 10 years, and the introduction of novel therapies such as targeted therapies and immunomodulators, the rather dark horizon of the median survival has dramatically changed from under 1 year to several years. With the advent of proteomics, deep-mining studies can reach low-abundant expression levels. The complexity of the proteome, however, still surpasses the dynam ...[more]

PMID: 31599373

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Project description:In recent years, high-throughput technologies have contributed to development a more precise picture of the human proteome. However, 2,129 proteins remain listed as missing proteins (MPs) in the newest neXtProt release (2019-02). The main reasons for MPs are a low abundance, low-molecular-weight (LMW), unexpected modifications, membrane characteristics, etc. Moreover, more than 50% of the MS/MS data have not been successfully identified in shotgun proteomics. Open-pFind, an efficient open search engine, recently released by the pFind group in China, presents an opportunity to identify these buried MPs in complex samples. Proteins and potential MPs were identified using Open-pFind and three other search engines to compare their performance and efficiency with three large-scale datasets digested by different enzymes. Our results demonstrated that Open-pFind identified 29.9-47.5% more peptide-spectrum matches (PSMs), 48.0-63.9% more peptides sequences (with modifications) and 22.7-38.1% more peptide sequences (regardless of modifications) than those identified by the second-best search engine. As a result, Open-pFind detected 7.5-19.3% more candidate MPs than those by the second-best search engine. In total, 5 (PE2) of the 150 candidate MPs identified by Open-pFind were verified from two unique peptides containing more than 9 amino acids (AA) by using spectrum theoretical prediction with pDeep, and synthesized peptide matching with pBuild, after spectrum quality analysis, isobaric post-translational modification, and single amino acid variant (SAAV) filtering. These five verified MPs can be ranked in the PE1 level. In addition, three other candidate MPs were verified with two unique peptides (one peptide containing more than 9 AA) and the other containing only 8 AA), which were slightly lower than the criteria listed by C-HPP, and required additional verification information. More importantly, unexpected modifications were detected in these MPs. Another 141 MPs were listed as candidates, but required additional verification information.