Recent advances in phosphoproteomics and application to neurological diseases

Arrington, Justine; Hsu, Chuan‐Chih; Elder, Sarah G.; Tao, W. Andy

doi:10.1039/c7an00985b

Cited by 35 publications

(33 citation statements)

References 227 publications

(224 reference statements)

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“…This results in a rather high demand for material compared to proteomics, which can hinder the employment of phosphoproteomics. For quantification, metabolic or chemical labeling is frequently employed, but label-free approaches are available as well (Arrington et al 2017). Current phosphoproteomics studies identified up to 20000 phosphorylation sites (von Stechow et al 2015).…”

Section: Which Omics Layers To Use For Toxicological Research Questionsmentioning

confidence: 99%

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Prospects and challenges of multi-omics data integration in toxicology

et al. 2020

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Exposure of cells or organisms to chemicals can trigger a series of effects at the regulatory pathway level, which involve changes of levels, interactions, and feedback loops of biomolecules of different types. A single-omics technique, e.g., transcriptomics, will detect biomolecules of one type and thus can only capture changes in a small subset of the biological cascade. Therefore, although applying single-omics analyses can lead to the identification of biomarkers for certain exposures, they cannot provide a systemic understanding of toxicity pathways or adverse outcome pathways. Integration of multiple omics data sets promises a substantial improvement in detecting this pathway response to a toxicant, by an increase of information as such and especially by a systemic understanding. Here, we report the findings of a thorough evaluation of the prospects and challenges of multi-omics data integration in toxicological research. We review the availability of such data, discuss options for experimental design, evaluate methods for integration and analysis of multi-omics data, discuss best practices, and identify knowledge gaps. Re-analyzing published data, we demonstrate that multi-omics data integration can considerably improve the confidence in detecting a pathway response. Finally, we argue that more data need to be generated from studies with a multi-omics-focused design, to define which omics layers contribute most to the identification of a pathway response to a toxicant.Archives of Toxicology (2020) 94:371-388Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Section: Which Omics Layers To Use For Toxicological Research Questionsmentioning

confidence: 99%

“…Many signaling pathways include phosphorylation reactions and an association of these phosphorylation sites to the pathways is readily possible. Other phosphorylation sites require additional experiments to associate them to a specific kinase and thus to a pathway (Arrington et al 2017).…”

Section: Which Omics Layers To Use For Toxicological Research Questionsmentioning

confidence: 99%

Prospects and challenges of multi-omics data integration in toxicology

et al. 2020

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“…There are many types of PTMs, including phosphorylation, methylation, palmitoylation, glycosylation, acetylation, SUMOylation, ubiquitination, and S-nitrosylation. Phospho-proteomics can map differential phosphorylation of kinases and phosphatases and their substrates, and it has been used to identify novel altered pathways in AD, ASD, and other neurological disorders [47]. For example, investigation of the phospho-proteome in AD cell line models and post-mortem brain samples has revealed the involvement of specific kinases in heat shock proteindependent protein folding, insulin-mediated signaling, p53 regulation, and neuronal autophagy [48][49][50].…”

Section: Identifying and Quantifying Post-translation Modificationsmentioning

confidence: 99%

Emerging proteomic approaches to identify the underlying pathophysiology of neurodevelopmental and neurodegenerative disorders

Murtaza

Singh

2020

Molecular Autism

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Proteomics is the large-scale study of the total protein content and their overall function within a cell through multiple facets of research. Advancements in proteomic methods have moved past the simple quantification of proteins to the identification of post-translational modifications (PTMs) and the ability to probe interactions between these proteins, spatially and temporally. Increased sensitivity and resolution of mass spectrometers and sample preparation protocols have drastically reduced the large amount of cells required and the experimental variability that had previously hindered its use in studying human neurological disorders. Proteomics offers a new perspective to study the altered molecular pathways and networks that are associated with autism spectrum disorders (ASD). The differences between the transcriptome and proteome, combined with the various types of post-translation modifications that regulate protein function and localization, highlight a novel level of research that has not been appropriately investigated. In this review, we will discuss strategies using proteomics to study ASD and other neurological disorders, with a focus on how these approaches can be combined with induced pluripotent stem cell (iPSC) studies. Proteomic analysis of iPSC-derived neurons have already been used to measure changes in the proteome caused by patient mutations, analyze changes in PTMs that resulted in altered biological pathways, and identify potential biomarkers. Further advancements in both proteomic techniques and human iPSC differentiation protocols will continue to push the field towards better understanding ASD disease pathophysiology. Proteomics using iPSC-derived neurons from individuals with ASD offers a window for observing the altered proteome, which is necessary in the future development of therapeutics against specific targets. Autism spectrum disorders

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“…The abnormal activity of protein kinases may induce several human diseases [6][7][8]. Especially, it has been found that there are lots of highly sensitive and specific phosphorylated proteins or peptides in the body fluids or tissues from cancer patients, indicating that phosphorylation by the specific kinase is closely related to the occurrence and development of cancers [9][10][11][12]. Various assay systems, including mass spectrometry [13], radioactivity [14], immunoprecipitation [15], fluorescence [16][17][18][19], colorimetry [20], and electrochemistry [21][22][23] based methods, have been developed for the detection of protein kinases and the corresponding phosphorylated substrates.…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation-Dependent SERS Readout for Activity Assay of Protein Kinase A in Cell Extracts

et al. 2020

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Protein kinases are key regulators of cell function, the abnormal activity of which may induce several human diseases, including cancers. Therefore, it is of great significance to develop a sensitive and reliable method for assaying protein kinase activities in real biological samples. Here, we report the phosphorylation-dependent surface-enhanced Raman scattering (SERS) readout of spermine-functionalized silver nanoparticles (AgNPs) for protein kinase A (PKA) activity assay in cell extracts. In this assay, the presence of PKA would phosphorylate and alter the net charge states of Raman dye-labeled substrate peptides, and the resulting anionic products could absorb onto the AgNPs with cationic surface charge through electrostatic attraction. Meanwhile, the Raman signals of dyes labeled on peptides were strongly enhanced by the aggregated AgNPs with interparticle hot spots formed in assay buffer. The SERS readout was directly proportional to the PKA activity in a wide range of 0.0001–0.5 U·μL−1 with a detection limit as low as 0.00003 U·μL−1. Moreover, the proposed SERS-based assay for the PKA activity was successfully applied to monitoring the activity and inhibition of PKA in real biological samples, particularly in cell extracts, which would be beneficial for kinase-related disease diagnostics and inhibitor screening.

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Recent advances in phosphoproteomics and application to neurological diseases

Cited by 35 publications

References 227 publications

Prospects and challenges of multi-omics data integration in toxicology

Prospects and challenges of multi-omics data integration in toxicology

Emerging proteomic approaches to identify the underlying pathophysiology of neurodevelopmental and neurodegenerative disorders

Phosphorylation-Dependent SERS Readout for Activity Assay of Protein Kinase A in Cell Extracts

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