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Looking for Missing Proteins in the Proteome Of Looking for Missing Proteins in the Proteome of Human Spermatozoa: An Update Yves Vandenbrouck, Lydie Lane, Christine Carapito, Paula Duek, Karine Rondel, Christophe Bruley, Charlotte Macron, Anne Gonzalez de Peredo, Yohann Coute, Karima Chaoui, et al. To cite this version: Yves Vandenbrouck, Lydie Lane, Christine Carapito, Paula Duek, Karine Rondel, et al.. Looking for Missing Proteins in the Proteome of Human Spermatozoa: An Update. Journal of Proteome Research, American Chemical Society, 2016, 15 (11), pp.3998-4019. 10.1021/acs.jproteome.6b00400. hal-02191502 HAL Id: hal-02191502 https://hal.archives-ouvertes.fr/hal-02191502 Submitted on 19 Mar 2021 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Journal of Proteome Research 1 2 3 Looking for missing proteins in the proteome of human spermatozoa: an 4 update 5 6 Yves Vandenbrouck1,2,3,#,§, Lydie Lane4,5,#, Christine Carapito6, Paula Duek5, Karine Rondel7, 7 Christophe Bruley1,2,3, Charlotte Macron6, Anne Gonzalez de Peredo8, Yohann Couté1,2,3, 8 Karima Chaoui8, Emmanuelle Com7, Alain Gateau5, AnneMarie Hesse1,2,3, Marlene 9 Marcellin8, Loren Méar7, Emmanuelle MoutonBarbosa8, Thibault Robin9, Odile Burlet- 10 Schiltz8, Sarah Cianferani6, Myriam Ferro1,2,3, Thomas Fréour10,11, Cecilia Lindskog12,Jérôme 11 1,2,3 7,§ 12 Garin , Charles Pineau . 13 14 1. CEA, DRF, BIG, Laboratoire de Biologie à Grande Echelle, 17 rue des martyrs, Grenoble, F- 15 38054, France 2. Inserm U1038, 17, rue des Martyrs, Grenoble F-38054, France 16 3. Université de Grenoble, Grenoble F-38054, France 17 4. Department of Human Protein Sciences, Faculty of medicine, University of Geneva, 1, rue 18 Michel-Servet, 1211 Geneva 4, Switzerland 19 5. CALIPHO Group, SIB-Swiss Institute of Bioinformatics, CMU, rue Michel-Servet 1, CH-1211 20 Geneva 4, Switzerland 6. Laboratoire de Spectrométrie de Masse BioOrganique (LSMBO), IPHC, Université de 21 Strasbourg, CNRS UMR7178, 25 Rue Becquerel, 67087 Strasbourg, France 22 7. Protim, Inserm U1085, Irset, Campus de Beaulieu, Rennes, 35042, France 23 8. Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, 24 France 25 9. Proteome Informatics Group, Centre Universitaire d'Informatique, Route de Drize 7, 1227 Carouge, CH, Switzerland 26 10. Service de Médecine de la Reproduction, CHU de Nantes, 38 boulevard Jean Monnet, 44093 27 Nantes cedex, France 28 11. INSERM UMR1064, Nantes, France 29 12. Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala 30 University, Uppsala, Sweden 31 32 #: Contributed equally to this work 33 34 §: Corresponding authors contact information: 35 [email protected], tel: +33 (0)4 38 78 26 74, fax: (33) (0)4 38 78 50 32; Charles 36 Pineau: [email protected], tel: +33 (0)2 23 23 52 79 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Journal of Proteome Research 1 2 3 4 Email addresses: 5 6 YV: [email protected] 7 LL: [email protected] 8 CC: [email protected] 9 PD: [email protected] 10 KR: [email protected] 11 CB: [email protected] 12 CM: [email protected] 13 AGP: [email protected] 14 YC: [email protected] 15 KC: [email protected] 16 EC: [email protected] 17 AG: [email protected] 18 AMH: [email protected] 19 MM: [email protected] 20 LM: [email protected] 21 EMB: [email protected] 22 TB: [email protected] 23 SC: [email protected] 24 OBS: [email protected] 25 MF: [email protected] 26 TF: [email protected] 27 CL: [email protected] 28 JG: [email protected] 29 30 CP: [email protected] 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Journal of Proteome Research 1 2 3 4 The mass spectrometry data used for proteomics have been deposited with the 5 ProteomeXchange Consortium via the PRIDE partner repository under dataset 6 identifier PXD003947 7 Reviewers can access our data using the following account details: 8 Project Name: Quest for missing proteins in the human spermatozoa: an update 9 Project accession: PXD003947 10 Project DOI: 10.6019/PXD003947 11 Reviewer account details: 12 Username: [email protected] 13 Password: v8rRsNI3 14 15 16 17 18 19 20 Keywords: human proteome project, spermatozoon, missing proteins, mass spectrometry 21 proteomics, immunohistochemistry, bioinformatics, data mining, cilia 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Journal of Proteome Research 1 2 3 Abstract 4 5 The Chromosome-Centric Human Proteome Project aims to identify proteins classed 6 7 as « missing » in the neXtProt knowledgebase. In this article, we present an in-depth 8 9 10 proteomics analysis of the human sperm proteome to identify testis-enriched missing 11 12 proteins. Using a range of protein extraction procedures and LC-MS/MS analysis, we 13 14 detected a total of 235 proteins (PE2-PE4) for which no previous evidence of protein 15 16 expression was annotated. Through a combination of LC-MS/MS and LC-PRM 17 18 analysis, data mining and immunohistochemistry, we were able to confirm the 19 20 21 expression of 206 missing proteins (PE2-4) in line with current HPP guidelines 22 23 (version 2.0). Parallel Reaction Monitoring (PRM) acquisition combined with synthetic 24 25 heavy labeled peptides was used to target 36 « onehit wonder » candidates selected 26 27 on the basis of prior PSM assessment. Of this subset of candidates, 24 were 28 29 30 validated with additional predicted and specifically targeted peptides. Evidence was 31 32 found for a further 16 missing proteins using immunohistochemistry on human testis 33 34 sections. The expression pattern for some of these proteins was specific to the testis, 35 36 and they could potentially be valuable markers with applications in fertility 37 38 assessment. Strong evidence was also found for the existence of 4 proteins labeled 39 40 41 as “uncertain” (PE5); the status of these proteins should therefore be re-examined. 42 43 Our results show how the use of a range of sample preparation techniques combined 44 45 with MS-based analysis, expert knowledge and complementary antibody-based 46 47 techniques can produce data of interest to the community. All MS/MS data are 48 49 50 available via ProteomeXchange under identifier PXD003947. In addition to 51 52 contributing to the Chromosome-Centric Human Proteome Project, we hope the 53 54 55 56 57 58 59 60 Journal of Proteome Research 1 2 3 availability of these data will stimulate the continued exploration of the sperm 4 5 proteome. 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Journal of Proteome Research 1 2 3 Introduction 4 5 The Chromosome-Centric Human Proteome Project (C-HPP) aims to catalogue the 6 7 1 8 protein gene products encoded by the human genome, in a gene-centric manner . 9 10 11 As part of this project, neXProt 2 has been confirmed as the reference 12 13 14 knowledgebase for human protein annotation 3. Numerous initiatives were launched 15 16 17 worldwide to search for so-called missing proteins - proteins predicted by genomic or 18 19 20 transcriptomic analysis, but not yet validated experimentally by mass-spectrometry or 21 22 antibody-based techniques. These proteins are annotated with a “Protein Existence” 23 24 (PE) score of 2 when they are predicted by transcriptomics analysis, 3 when they are 25 26 predicted by genomic analysis and have homologs in distant species, and 4 when 27 28 29 they are only predicted by genomic analysis in human or other mammals. The most 30 31 recent neXtProt release (2016-01-11) contains 2949 such missing proteins. It was 32 33 suggested by Lane and collaborators 4 that proteins that have been systematically 34 35 36 missed might be expressed only in a few organs or cell types. The very high number 37 38 39 of testis-specific genes that have been described 5 supports the hypothesis that the 40 41 42 testis is a promising organ in which to search for elements of the missing proteome 6 43 44 45 7 46 . The testis’ main function is well known: to produce male gametes, known as 47 48 49 spermatozoa (commonly called sperm). Human spermatozoa are produced at a rate 50 51 of about 1,000 cells/sec 8 by a complex, intricate, tightly controlled and specialized 52 53 54 process known as spermatogenesis 9 10. Spermiogenesis is the final stage of 55 56 57 58 59 60 Journal of Proteome Research 1 2 3 spermatogenesis, which sees the maturation of spermatids into mature, motile 4 5 spermatozoa.
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