Missing Protein Landscape of Human Chromosomes 2 and 14: Progress and Current Status

Duek, Paula D.; Bairoch, Amos Marc; Gateau, Alain; Vandenbrouck, Yves; Lane, Lydie

doi:10.1021/acs.jproteome.6b00443

Cited by 15 publications

(27 citation statements)

References 23 publications

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“…Based on RNA-Seq data from HPA, six MPs for which we obtained mass spectrometry evidence in sperm (FAM181A, DNAJC5G, LRRC9, ALLC, C2orf78, 17 MAP3K19) correspond to genes showing a medium expression level in testis (between 10 and 100 transcripts per million, TPM), seven others (ADAM20, TEX22, EVX2, SLC35F4, FER1L5, KIAA2012 and ANKRD30BL) correspond to genes with a low expression level (less than 10 TPM) and two others to genes for which the expression in testis was validated by quantitative RT-PCR while no RNA-Seq data was reported (HERVs) 14 .…”

Section: Targeted Ms Results Support Data Mining Prioritization Strategymentioning

confidence: 99%

Validating Missing Proteins in Human Sperm Cells by Targeted Mass-Spectrometry- and Antibody-based Methods

et al. 2017

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The present study is a contribution to the "neXt50 challenge", a coordinated effort across C-HPP teams to identify the 50 most tractable missing proteins (MPs) on each chromosome. We report the targeted search of 38 theoretically detectable MPs from chromosomes 2 and 14 in Triton X-100 soluble and insoluble sperm fractions from a total of 15 healthy donors. A targeted mass-spectrometry-based strategy consisting of the development of LC-PRM assays (with heavy labeled synthetic peptides) targeting 92 proteotypic peptides of the 38 selected MPs was used. Out of the 38 selected MPs, 12 were identified with two or more peptides and 3 with one peptide after extensive SDS-PAGE fractionation of the two samples and with overall low-intensity signals. The PRM data are available via ProteomeXchange in PASSEL (PASS01013). Further validation by immunohistochemistry on human testes sections and cytochemistry on sperm smears was performed for eight MPs with antibodies available from the Human Protein Atlas. Deep analysis of human sperm still allows the validation of MPs and therefore contributes to the C-HPP worldwide effort. We anticipate that our results will be of interest to the reproductive biology community because an in-depth analysis of these MPs may identify potential new candidates in the context of human idiopathic infertilities.

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Section: Targeted Ms Results Support Data Mining Prioritization Strategymentioning

confidence: 99%

Validating Missing Proteins in Human Sperm Cells by Targeted Mass-Spectrometry- and Antibody-based Methods

et al. 2017

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“…In this JPR issue, follow-up papers from each of those groups extend these findings with 206 additional missing proteins from sperm (Vandenbrouck et al, 42 PXD003947) and 47 additional missing proteins from testis (Wei et al, 43 iProx00076500) identified under the new guidelines. In addition, Duek et al 44 have presented an outstanding analysis of chromosomes 2 and 14 for missing proteins, theoretically detectable proteins, and proteins most promising for SRM analysis in sperm.…”

Section: Concluding Remarks and New Directionsmentioning

confidence: 99%

Metrics for the Human Proteome Project 2016: Progress on Identifying and Characterizing the Human Proteome, Including Post-Translational Modifications

et al. 2016

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The HUPO Human Proteome Project (HPP) has two overall goals: (1) stepwise completion of the protein parts list—the draft human proteome including confidently identifying and characterizing at least one protein product from each protein-coding gene, with increasing emphasis on sequence variants, post-translational modifications (PTMs), and splice isoforms of those proteins; and (2) making proteomics an integrated counterpart to genomics throughout the biomedical and life sciences community. PeptideAtlas and GPMDB reanalyze all major human mass spectrometry data sets available through ProteomeXchange with standardized protocols and stringent quality filters; neXtProt curates and integrates mass spectrometry and other findings to present the most up to date authorative compendium of the human proteome. The HPP Guidelines for Mass Spectrometry Data Interpretation version 2.1 were applied to manuscripts submitted for this 2016 C-HPP-led special issue [www.thehpp.org/guidelines]. The Human Proteome presented as neXtProt version 2016-02 has 16,518 confident protein identifications (Protein Existence [PE] Level 1), up from 13,664 at 2012-12, 15,646 at 2013-09, and 16,491 at 2014-10. There are 485 proteins that would have been PE1 under the Guidelines v1.0 from 2012 but now have insufficient evidence due to the agreed-upon more stringent Guidelines v2.0 to reduce false positives. neXtProt and PeptideAtlas now both require two non-nested, uniquely mapping (proteotypic) peptides of at least 9 aa in length. There are 2,949 missing proteins (PE2+3+4) as the baseline for submissions for this fourth annual C-HPP special issue of Journal of Proteome Research. PeptideAtlas has 14,629 canonical (plus 1187 uncertain and 1755 redundant) entries. GPMDB has 16,190 EC4 entries, and the Human Protein Atlas has 10,475 entries with supportive evidence. neXtProt, PeptideAtlas, and GPMDB are rich resources of information about post-translational modifications (PTMs), single amino acid variants (SAAVSs), and splice isoforms. Meanwhile, the Biology- and Disease-driven (B/D)-HPP has created comprehensive SRM resources, generated popular protein lists to guide targeted proteomics assays for specific diseases, and launched an Early Career Researchers initiative.

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“…In particular for PE2 proteins, C-HPP investigators can approach to perform target proteomics in order to identify PE2 class MPs by utilizing genomics dataset (e.g., RNA-seq) obtained from some specific tissues or cell lines [30]. Duek et al, attempted to detect MPs from testis by analyzing RNA-seq data and proteomic profiling with MRM assays [38, 39]. …”

Section: Challenges For the C-hppmentioning

confidence: 99%

Advances in the Chromosome-Centric Human Proteome Project: looking to the future

Paik

Omenn

Hancock

et al. 2017

Expert Review of Proteomics

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Introduction: The mission of the Chromosome-Centric Human Proteome Project (C-HPP), is to map and annotate the entire predicted human protein set (~20,000 proteins) encoded by each chromosome. The initial steps of the project are focused on “missing proteins (MPs)”, which lacked documented evidence for existence at protein level. In addition to remaining 2,579 MPs, we also target those annotated proteins having unknown functions, uPE1 proteins, alternative splice isoforms and post-translational modifications. We also consider how to investigate various protein functions involved in cis-regulatory phenomena, amplicons lncRNAs and smORFs. Areas covered: We will cover the scope, historic background, progress, challenges and future prospects of C-HPP. This review also addresses the question of how we can best improve the methodological approaches, select the optimal biological samples, and recommend stringent protocols for the identification and characterization of MPs. A new strategy for functional analysis of some of those annotated proteins having unknown function will also be discussed. Expert commentary: If the project moves well by reshaping the original goals, the current working modules and team work in the proposed extended planning period, it is anticipated that a progressively more detailed draft of an accurate chromosome-based proteome map will become available with functional information.

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Missing Protein Landscape of Human Chromosomes 2 and 14: Progress and Current Status

Cited by 15 publications

References 23 publications

Validating Missing Proteins in Human Sperm Cells by Targeted Mass-Spectrometry- and Antibody-based Methods

Validating Missing Proteins in Human Sperm Cells by Targeted Mass-Spectrometry- and Antibody-based Methods

Metrics for the Human Proteome Project 2016: Progress on Identifying and Characterizing the Human Proteome, Including Post-Translational Modifications

Advances in the Chromosome-Centric Human Proteome Project: looking to the future

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