Accelerating the search for the missing proteins in the human proteome

Baker, Mark S.; Ahn, Seong Beom; Mohamedali, Abidali; Islam, Mohammad Tawhidul; Cantor, David; Verhaert, Peter; Fanayan, Susan; Sharma, Samridhi; Nice, Edouard C.; Connor, Mark; Ranganathan, Shoba

doi:10.1038/ncomms14271

Cited by 90 publications

(108 citation statements)

References 60 publications

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“…These improvements allowed achieving a number of milestones within the Human Proteome Project and other global proteomic initiatives . Among the recent achievements is, for example, the identification at the proteome level of most of the protein coding reading frames predicted before from the genome sequence …”

Section: Introductionmentioning

confidence: 99%

Adenosine‐to‐Inosine RNA Editing in Mouse and Human Brain Proteomes

et al. 2019

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Proteogenomics is based on the use of customized genome or RNA sequencing databases for interrogation of shotgun proteomics data in search for proteome‐level evidence of genome variations or RNA editing. In this work, the products of adenosine‐to‐inosine RNA editing in human and murine brain proteomes are identified using publicly available brain proteome LC‐MS/MS datasets and an RNA editome database compiled from several sources. After filtering of false‐positive results, 20 and 37 sites of editing in proteins belonging to 14 and 32 genes are identified for murine and human brain proteomes, respectively. Eight sites of editing identified with high spectral counts overlapped between human and mouse brain samples. Some of these sites have been previously reported using orthogonal methods, such as α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) glutamate receptors, CYFIP2, coatomer alpha. Also, differential editing between neurons and microglia is demonstrated in this work for some of the proteins from primary murine brain cell cultures. Because many edited sites are still not characterized functionally at the protein level, the results provide a necessary background for their further analysis in normal and diseased cells and tissues using targeted proteomic approaches.

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Section: Introductionmentioning

confidence: 99%

Adenosine‐to‐Inosine RNA Editing in Mouse and Human Brain Proteomes

et al. 2019

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“…The first is based on technical sensitivity, as low abundance proteins are difficult to detect and not all of the proteins have been identified. It is estimated that ≈80% of the proteins in humans have been detected with high‐confidence, but the remaining 20% of proteins have not been identifiable with current experimental methods . Additionally, protein and transcript levels do not always overlap so transcriptomic and proteomic analyses may not be directly comparable.…”

Section: Discussionmentioning

confidence: 99%

In Vitro and In Vivo Proteomic Comparison of Human Neural Progenitor Cell‐Induced Photoreceptor Survival

et al. 2019

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Retinal degenerative diseases lead to blindness with few treatments. Various cell‐based therapies are aimed to slow the progression of vision loss by preserving light‐sensing photoreceptor cells. A subretinal injection of human neural progenitor cells (hNPCs) into the Royal College of Surgeons (RCS) rat model of retinal degeneration has aided in photoreceptor survival, though the mechanisms are mainly unknown. Identifying the retinal proteomic changes that occur following hNPC treatment leads to better understanding of neuroprotection. To mimic the retinal environment following hNPC injection, a co‐culture system of retinas and hNPCs is developed. Less cell death occurs in RCS retinal tissue co‐cultured with hNPCs than in retinas cultured alone, suggesting that hNPCs provide retinal protection in vitro. Comparison of ex vivo and in vivo retinas identifies nuclear factor (erythroid‐derived 2)‐like 2 (NRF2) mediated oxidative response signaling as an hNPC‐induced pathway. This is the first study to compare proteomic changes following treatment with hNPCs in both an ex vivo and in vivo environment, further allowing the use of ex vivo modeling for mechanisms of retinal preservation. Elucidation of the protein changes in the retina following hNPC treatment may lead to the discovery of mechanisms of photoreceptor survival and its therapeutic for clinical applications.

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“…The ORs form a multigene family consisting of around 1,000 genes in humans, but only ~400 functional genes code for ORs; the remaining 600 candidates are pseudogenes [71,72]. These latter ORs are indeed the best examples of a so-called black box in the proteomics field, although their coding genes are distributed over almost all the chromosomes [73]. For instance, the PeptideAtlas has reevaluated its OR entries and has eliminated the two remaining entries as of 2014 [14].…”

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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Accelerating the search for the missing proteins in the human proteome

Cited by 90 publications

References 60 publications

Adenosine‐to‐Inosine RNA Editing in Mouse and Human Brain Proteomes

Adenosine‐to‐Inosine RNA Editing in Mouse and Human Brain Proteomes

In Vitro and In Vivo Proteomic Comparison of Human Neural Progenitor Cell‐Induced Photoreceptor Survival

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

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