Progress on the HUPO Draft Human Proteome: 2017 Metrics of the Human Proteome Project

Omenn, Gilbert S.; Lane, Lydie; Lundberg, Emma; Overall, Christopher M.; Deutsch, Eric W.

doi:10.1021/acs.jproteome.7b00375

Cited by 57 publications

(87 citation statements)

References 52 publications

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“…The latest HPP guidelines 2.1.0 require identification of two uniquely mapping non‐nested peptides with a minimum length of nine amino acids to qualify a protein as known (PE1). Exceptions are allowed only for the proteins that can never meet this requirements . All proteins annotated with PE 2–4 level of evidence are classified as “missing proteins.” To accumulate evidence at the protein level for missing proteins, we compared the proteins identified in this study against list of “missing proteins” in neXtProt (release date: January 17, 2018).…”

Section: Resultsmentioning

confidence: 99%

Integrated Transcriptomic and Proteomic Analysis of Primary Human Umbilical Vein Endothelial Cells

Madugundu

Nirujogi

et al. 2019

Proteomics

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Understanding the molecular profile of every human cell type is essential for understanding its role in normal physiology and disease. Technological advancements in DNA sequencing, mass spectrometry and computational methods allow us to carry out multi-Omics analyses although such approaches are not routine yet. Human umbilical vein endothelial cells (HUVECs) are a widely-used model system to study pathological and physiological processes associated with the cardiovascular system. In this study, we employed next generation sequencing and high-resolution mass spectrometry to profile the transcriptome and proteome of primary HUVECs. Analysis of 145 million paired-end reads from next generation sequencing confirmed expression of 12,186 protein-coding genes (FPKM≥0.1), 439 novel long non-coding RNAs and revealed 6,089 novel isoforms that were not annotated in GENCODE. Proteomics analysis identified 6,477 proteins including confirmation of N-termini for 1,091 proteins, isoforms for 149 proteins and 1,034 phosphosites. A database search to specifically identify other post-translational modifications provided evidence for a number of modification sites on 117 proteins which included ubiquitylation, lysine acetylation and mono, di- and tri-methylation events. Based on the data from this study and a survey of other databases, we provide evidence for 11 “missing proteins,” which are proteins for which there was insufficient or no protein level evidence. Peptides supporting missing protein and novel events were validated by comparison of MS/MS fragmentation patterns with synthetic peptides. Finally, we identified 245 variant peptides derived from 207 expressed proteins in addition to alternate translational start sites for seven proteins and evidence for novel proteoforms for five proteins resulting from alternative splicing. Overall, we believe that the integrated approach employed in this study is widely applicable to study any primary cell type for deeper molecular characterization.

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Section: Resultsmentioning

confidence: 99%

Integrated Transcriptomic and Proteomic Analysis of Primary Human Umbilical Vein Endothelial Cells

Madugundu

Nirujogi

et al. 2019

Proteomics

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“…Another well‐known issue in proteomics is the “missing proteins” problem, referring to annotated genes with undiscovered protein counterparts; and the Chromosome Centric Human Proteome Project (C‐HPP) is among the leaders in this research domain . For example, in a study addressing chromosome 12, Manda et.…”

Section: Applications Of Proteogenomics In Biologymentioning

confidence: 99%

Connecting Proteomics to Next‐Generation Sequencing: Proteogenomics and Its Current Applications in Biology

et al. 2018

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Understanding the relationship between genotypes and phenotypes is essential to disentangle biological mechanisms and to unravel the molecular basis of diseases. Genes and proteins are closely linked in biological systems. However, genomics and proteomics have developed separately into two distinct disciplines whereby crosstalk among scientists from the two domains is limited and this constrains the integration of both fields into a single data modality of useful information. The emerging field of proteogenomics attempts to address this by building bridges between the two disciplines. In this review, how genomics and transcriptomics data in different formats can be utilized to assist proteogenomics application is briefly discussed. Subsequently, a much larger part of this review focuses on proteogenomics research articles that are published in the last five years that answer two important questions. First, how proteogenomics can be applied to tackle biological problems is discussed, covering genome annotation and precision medicine. Second, the latest developments in analytical technologies for data acquisition and the bioinformatics tools to interpret and visualize proteogenomics data are covered.

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“…To this end, the C-HPP is also focusing on alternative splice isoforms and post-translational modifications (PTMs) (phosphorylations, glycosylations, acetylations). In addition to the expected products of the ~20,000 predicted protein-coding genes, claims of small open reading frame ORF (smORF) translation products (smORFs), and long non-coding (lnc) RNAs have recently gained attention [4, 5], and are actively investigated using new proteomics technologies.…”

Section: Scope Goals and And Deliverablesmentioning

confidence: 99%

“…However, there remain a lot more challenges to reach this goal due to uneven situations for each team with respect to funding, infrastructure and manpower. Scientifically, many challenges also await for those issues involved in splice variants and PTMs in the course of production of protein parts list [5]. …”

Section: Background History and Rationalementioning

confidence: 99%

“…It seems necessary to place an exception in the Guidelines v2.1 for such ‘non-MS MP detection’ (e.g., TBL1Y, prestin) in which other cellular and molecular evidences support the protein evidence [47, 48]. This issue has been well discussed in recent publication by Omenn et al, [5]. Briefly, as in case of some of proteins that were driven from lncRNAs or smORFs, HPP group may consider updating the current HPP data interpretation guidelines v2.1, checklist #15 [14] to deal with such extraordinary case in which weaker evidence is offered for an extraordinary protein or coding element detection (e.g., lacking lysine site-unsuitable for trypsin digestion), justify that other peptides cannot be expected.…”

Section: Challenges For the C-hppmentioning

confidence: 99%

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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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Progress on the HUPO Draft Human Proteome: 2017 Metrics of the Human Proteome Project

Cited by 57 publications

References 52 publications

Integrated Transcriptomic and Proteomic Analysis of Primary Human Umbilical Vein Endothelial Cells

Integrated Transcriptomic and Proteomic Analysis of Primary Human Umbilical Vein Endothelial Cells

Connecting Proteomics to Next‐Generation Sequencing: Proteogenomics and Its Current Applications in Biology

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

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