Open AccessReview
Proteomic Analysis of Histone Variants and Their PTMs: Strategies and Pitfalls
Proteomes 2018, 6(3), 29; https://doi.org/10.3390/proteomes6030029 -
Abstract
Epigenetic modifications contribute to the determination of cell fate and differentiation. The molecular mechanisms underlying histone variants and post-translational modifications (PTMs) have been studied in the contexts of development, differentiation, and disease. Antibody-based assays have classically been used to target PTMs, but these
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Epigenetic modifications contribute to the determination of cell fate and differentiation. The molecular mechanisms underlying histone variants and post-translational modifications (PTMs) have been studied in the contexts of development, differentiation, and disease. Antibody-based assays have classically been used to target PTMs, but these approaches fail to reveal combinatorial patterns of modifications. In addition, some histone variants are so similar to canonical histones that antibodies have difficulty distinguishing between these isoforms. Mass spectrometry (MS) has progressively developed as a powerful technology for the study of histone variants and their PTMs. Indeed, MS analyses highlighted exquisitely complex combinations of PTMs, suggesting “crosstalk” between them, and also revealed that PTM patterns are often variant-specific. Even though the sensitivity and acquisition speed of MS instruments have considerably increased alongside the development of computational tools for the study of multiple PTMs, it remains challenging to correctly describe the landscape of histone PTMs, and in particular to confidently assign modifications to specific amino acids. Here, we provide an inventory of MS-based strategies and of the pitfalls inherent to histone PTM and variant characterization, while stressing the complex interplay between PTMs and histone sequence variations. We will particularly illustrate the roles played by MS-based analyses in identifying and quantifying histone variants and modifications. Full article
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Open AccessFeature PaperEditorial
Editorial for Special Issue: 2017 Plant Proteomics
Proteomes 2018, 6(3), 28; https://doi.org/10.3390/proteomes6030028 -
Open AccessArticle
Large Scale Proteomic Data and Network-Based Systems Biology Approaches to Explore the Plant World
Proteomes 2018, 6(2), 27; https://doi.org/10.3390/proteomes6020027 -
Abstract
The investigation of plant organisms by means of data-derived systems biology approaches based on network modeling is mainly characterized by genomic data, while the potential of proteomics is largely unexplored. This delay is mainly caused by the paucity of plant genomic/proteomic sequences and
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The investigation of plant organisms by means of data-derived systems biology approaches based on network modeling is mainly characterized by genomic data, while the potential of proteomics is largely unexplored. This delay is mainly caused by the paucity of plant genomic/proteomic sequences and annotations which are fundamental to perform mass-spectrometry (MS) data interpretation. However, Next Generation Sequencing (NGS) techniques are contributing to filling this gap and an increasing number of studies are focusing on plant proteome profiling and protein-protein interactions (PPIs) identification. Interesting results were obtained by evaluating the topology of PPI networks in the context of organ-associated biological processes as well as plant-pathogen relationships. These examples foreshadow well the benefits that these approaches may provide to plant research. Thus, in addition to providing an overview of the main-omic technologies recently used on plant organisms, we will focus on studies that rely on concepts of module, hub and shortest path, and how they can contribute to the plant discovery processes. In this scenario, we will also consider gene co-expression networks, and some examples of integration with metabolomic data and genome-wide association studies (GWAS) to select candidate genes will be mentioned. Full article
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Open AccessFeature PaperReview
Potential Alternative Strategy against Drug Resistant Tuberculosis: A Proteomics Prospect
Proteomes 2018, 6(2), 26; https://doi.org/10.3390/proteomes6020026 -
Abstract
Mycobacterium tuberculosis is one of the deadliest human pathogen of the tuberculosis diseases. Drug resistance leads to emergence of multidrug-resistant and extremely drug resistant strains of M. tuberculosis. Apart from principal targets of resistance, many explanations have been proposed for drug resistance
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Mycobacterium tuberculosis is one of the deadliest human pathogen of the tuberculosis diseases. Drug resistance leads to emergence of multidrug-resistant and extremely drug resistant strains of M. tuberculosis. Apart from principal targets of resistance, many explanations have been proposed for drug resistance but some resistance mechanisms are still unknown. Recently approved line probe assay (LPA) diagnostics for detecting the resistance to first and second line drugs are unable to diagnose the drug resistance in M. tuberculosis isolates which do not have the mutations in particular genes responsible for resistance. Proteomics and bioinformatic tools emerged as direct approaches for identification and characterization of novel proteins which are directly and indirectly involved in drug resistance that could be used as potential targets in future. In future, these novel targets might reveal new mechanism of resistance and can be used in diagnostics or as drug targets. Full article
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Open AccessArticle
Proteomic Analysis of Aphid-Resistant and -Sensitive Rose (Rosa Hybrida) Cultivars at Two Developmental Stages
Proteomes 2018, 6(2), 25; https://doi.org/10.3390/proteomes6020025 -
Abstract
The rose is one the most commercially grown and costly ornamental plants because of its aesthetic beauty and aroma. A large number of pests attack its buds, flowers, leaves, and stem at every growing stage due to its high sugar content. The most
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The rose is one the most commercially grown and costly ornamental plants because of its aesthetic beauty and aroma. A large number of pests attack its buds, flowers, leaves, and stem at every growing stage due to its high sugar content. The most common pest on roses are aphids which are considered to be the major cause for product loss. Aphid infestations lead to major changes in rose plants, such as large and irregular holes in petals, intact leaves and devouring tissues. It is hypothesized that different cut rose cultivars would have different levels of sensitivity or resistance to aphids, since different levels of infestation are observed in commercially cut rose production greenhouses. The present work compared four cut rose cultivars which were bred in Korea and were either resistant or sensitive to aphid infestation at different flower developmental stages. An integrative study was conducted using comprehensive proteome analyses. Proteins related to ubiquitin metabolism and the stress response were differentially expressed due to aphid infestation. The regulations and possible functions of identified proteins are presented in detail. The differential expressions of the identified proteins were validated by immunoblotting and blue native page. In addition, total sugar and carbohydrate content were also observed. Full article
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Open AccessArticle
Utilizing Optimized Tools to Investigate PTM Crosstalk: Identifying Potential PTM Crosstalk of Acetylated Mitochondrial Proteins
Proteomes 2018, 6(2), 24; https://doi.org/10.3390/proteomes6020024 -
Abstract
Post-translational modification (PTM) crosstalk is recognized as a major cell-regulatory mechanism, and studies of several proteins have validated the premise that PTMs work in concert. Previous work by our group investigated the potential PTM crosstalk on proteins in the EGFR-Ras-c-Fos axis by utilizing
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Post-translational modification (PTM) crosstalk is recognized as a major cell-regulatory mechanism, and studies of several proteins have validated the premise that PTMs work in concert. Previous work by our group investigated the potential PTM crosstalk on proteins in the EGFR-Ras-c-Fos axis by utilizing a comprehensive set of PTM reagents termed Signal-Seeker toolkits. In this study, these tools were used to investigate the potential PTM crosstalk that occurs in acetylated mitochondrial proteins in response to a mitochondrial stress-inducing agent hydrogen peroxide (H2O2). Mitochondrial protein acetylation has been shown to participate in PTM crosstalk as exemplified by the regulation of the pyruvate dehydrogenase complex via kinase, phosphatase, acetyltransferase, and deacetylase activities. Changes in the acetylated state of mitochondrial proteins were investigated, in response to H2O2, using a novel anti acetyl lysine (Ac-K) antibody. Signal-Seeker PTM detection tools were used to validate the acetylation state of ten mitochondrial targets, as well as their endogenous acetylation state in response to H2O2. Importantly, the endogenous acetylation, ubiquitination, SUMOylation 2/3, and tyrosine phosphorylation state of four target mitochondrial proteins were also investigated with the toolkit. Each of the four proteins had unique PTM profiles, but diverging acetylation and ubiquitin or SUMO 2/3 signals appeared to be a common theme. This proof-of-concept study identifies the Signal-Seeker toolkits as a useful tool to investigate potential PTM crosstalk. Full article
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Open AccessFeature PaperReview
Virophages and Their Interactions with Giant Viruses and Host Cells
Proteomes 2018, 6(2), 23; https://doi.org/10.3390/proteomes6020023 -
Abstract
Virophages are small dsDNA viruses that were first isolated in association with some giant viruses (GVs), and then found in metagenomics samples. They encode about 20–34 proteins. Some virophages share protein similarity with Maverick/Polinton transposons or are considered as a provirophage, whereas about
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Virophages are small dsDNA viruses that were first isolated in association with some giant viruses (GVs), and then found in metagenomics samples. They encode about 20–34 proteins. Some virophages share protein similarity with Maverick/Polinton transposons or are considered as a provirophage, whereas about half of the protein’s repertoire remain of unknown function. In this review, we aim to highlight the current understanding of the biology of virophages, as well as their interactions with giant viruses and host cells. Additionally, the virophage proteomes were analyzed to find the functional domains that distinguish each virophage. This bioinformatics analysis will benefit further experimental investigations to understand the protein-protein interactions between virophages, giant viruses, and host cells. Full article
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Open AccessReview
Proteomics of Human Retinal Pigment Epithelium (RPE) Cells
Proteomes 2018, 6(2), 22; https://doi.org/10.3390/proteomes6020022 -
Abstract
Retinal pigment epithelium (RPE) are specialized, multifunctional cells in the retina that form a monolayer of cuboidal, polarized cells adjoining the photoreceptor cells. The RPE are a critical component of the blood-retinal barrier, and they play essential functional roles for maintenance of retinal
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Retinal pigment epithelium (RPE) are specialized, multifunctional cells in the retina that form a monolayer of cuboidal, polarized cells adjoining the photoreceptor cells. The RPE are a critical component of the blood-retinal barrier, and they play essential functional roles for maintenance of retinal homeostasis and for support and health of photoreceptors. Age-dependent, progressive dysfunction and death of RPE cells and the resultant loss of photoreceptors contribute significantly to the development and progression of age-related macular degeneration (AMD) and other retinal degenerative diseases. Several different RPE cell culture models have been developed and utilized extensively as surrogates for cellular and molecular examinations of the RPE, and a large body of knowledge on RPE function in normal and pathological scenarios has been amassed in studies with cultured RPE. Proteomics has been an integral part of research efforts aimed to advance our understanding of RPE cell biology in health and disease. This review focuses on applications of proteomics to in vitro qualitative and quantitative investigation of human RPE cell culture models. The disease context discussed focuses on AMD. Full article
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Open AccessReview
The Use of Proteomic Tools to Address Challenges Faced in Clonal Propagation of Tropical Crops through Somatic Embryogenesis
Proteomes 2018, 6(2), 21; https://doi.org/10.3390/proteomes6020021 -
Abstract
In many tropical countries with agriculture as the mainstay of the economy, tropical crops are commonly cultivated at the plantation scale. The successful establishment of crop plantations depends on the availability of a large quantity of elite seedling plants. Many plantation companies establish
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In many tropical countries with agriculture as the mainstay of the economy, tropical crops are commonly cultivated at the plantation scale. The successful establishment of crop plantations depends on the availability of a large quantity of elite seedling plants. Many plantation companies establish plant tissue culture laboratories to supply planting materials for their plantations and one of the most common applications of plant tissue culture is the mass propagation of true-to-type elite seedlings. However, problems encountered in tissue culture technology prevent its applications being widely adopted. Proteomics can be a powerful tool for use in the analysis of cultures, and to understand the biological processes that takes place at the cellular and molecular levels in order to address these problems. This mini review presents the tissue culture technologies commonly used in the propagation of tropical crops. It provides an outline of some the genes and proteins isolated that are associated with somatic embryogenesis and the use of proteomic technology in analysing tissue culture samples and processes in tropical crops. Full article
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Open AccessReview
Integrated Chemometrics and Statistics to Drive Successful Proteomics Biomarker Discovery
Proteomes 2018, 6(2), 20; https://doi.org/10.3390/proteomes6020020 -
Abstract
Protein biomarkers are of great benefit for clinical research and applications, as they are powerful means for diagnosing, monitoring and treatment prediction of different diseases. Even though numerous biomarkers have been reported, the translation to clinical practice is still limited. This mainly due
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Protein biomarkers are of great benefit for clinical research and applications, as they are powerful means for diagnosing, monitoring and treatment prediction of different diseases. Even though numerous biomarkers have been reported, the translation to clinical practice is still limited. This mainly due to: (i) incorrect biomarker selection, (ii) insufficient validation of potential biomarkers, and (iii) insufficient clinical use. In this review, we focus on the biomarker selection process and critically discuss the chemometrical and statistical decisions made in proteomics biomarker discovery to increase to selection of high value biomarkers. The characteristics of the data, the computational resources, the type of biomarker that is searched for and the validation strategy influence the decision making of the chemometrical and statistical methods and a decision made for one component directly influences the choice for another. Incorrect decisions could increase the false positive and negative rate of biomarkers which requires independent confirmation of outcome by other techniques and for comparison between different related studies. There are few guidelines for authors regarding data analysis documentation in peer reviewed journals, making it hard to reproduce successful data analysis strategies. Here we review multiple chemometrical and statistical methods for their value in proteomics-based biomarker discovery and propose to include key components in scientific documentation. Full article
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Open AccessArticle
A Proteomic View of Salmonella Typhimurium in Response to Phosphate Limitation
Proteomes 2018, 6(2), 19; https://doi.org/10.3390/proteomes6020019 -
Abstract
Salmonella enterica serovar Typhimurium (S. Typhimurium), an important foodborne pathogen, often encounters phosphate (Pi) shortage both in the environment and inside host cells. To gain a global view on its physiological responses to Pi starvation, we performed proteomic profiling
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Salmonella enterica serovar Typhimurium (S. Typhimurium), an important foodborne pathogen, often encounters phosphate (Pi) shortage both in the environment and inside host cells. To gain a global view on its physiological responses to Pi starvation, we performed proteomic profiling of S. Typhimurium upon the shift from Pi-rich to Pi-low conditions. In addition to the Pho regulon, many metabolic processes were up-regulated, such as glycolysis, pentose phosphate pathway, pyrimidine degradation, glycogen, and trehalose metabolism, allowing us to chart an overview of S. Typhimurium carbon metabolism under Pi starvation. Furthermore, proteomic analysis of a mutant lacking phoB (that encodes a key regulator of Pi shortage response) suggested that only a small subset of the altered proteins upon Pi limitation was PhoB-dependent. Importantly, we present evidence that S. Typhimurium N-acetylglucosamine catabolism was induced under Pi-limiting conditions in a PhoB-dependent manner. Immunoblotting and β-galactosidase assays demonstrated that PhoB was required for the full activation of NagB, a key enzyme of this pathway, in response to low Pi. Thus, our study reveals that N-acetylglucosamine catabolism may represent an additional PhoB-regulated pathway to tackle bacterial Pi shortage. Full article
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Open AccessFeature PaperArticle
Surface and Extracellular Proteome of the Emerging Pathogen Corynebacterium ulcerans
Proteomes 2018, 6(2), 18; https://doi.org/10.3390/proteomes6020018 -
Abstract
Corynebacterium ulcerans is an emerging pathogen, which is increasingly recognized as an etiological agent of diphtheria, but can also evoke ulcers of the skin and systemic infections in humans. Besides man, the bacteria can colonize a wide variety of different animals, including cattle
[...] Read more.
Corynebacterium ulcerans is an emerging pathogen, which is increasingly recognized as an etiological agent of diphtheria, but can also evoke ulcers of the skin and systemic infections in humans. Besides man, the bacteria can colonize a wide variety of different animals, including cattle and pet animals, which might serve as a reservoir for human infections. In this study, surface-located proteins and the exoproteome of two Corynebacterium ulcerans strains were analyzed, since these may have key roles in the interaction of the pathogen with host cells. Strain 809 was isolated from a fatal case of human respiratory tract infection, while strain BR-AD22 was isolated from a nasal swap of an asymptomatic dog. While a very similar pattern of virulence factors was observed in the culture supernatant and surface protein fractions of the two strains, proteome analyses revealed a higher stability of 809 cells compared to strain BR-AD22. During exponential growth, 17% of encoded proteins of strain 809 were detectable in the medium, while 38% of the predicted proteins encoded by the BR-AD22 chromosome were found. Furthermore, the data indicate differential expression of phospholipase D and a cell wall-associated hydrolase, since these were only detected in strain BR-AD22. Full article
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Open AccessReview
Molecular Pathophysiology of Epithelial Barrier Dysfunction in Inflammatory Bowel Diseases
Proteomes 2018, 6(2), 17; https://doi.org/10.3390/proteomes6020017 -
Abstract
Over the years, the scientific community has explored myriads of theories in search of the etiology and a cure for inflammatory bowel disease (IBD). The cumulative evidence has pointed to the key role of the intestinal barrier and the breakdown of these mechanisms
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Over the years, the scientific community has explored myriads of theories in search of the etiology and a cure for inflammatory bowel disease (IBD). The cumulative evidence has pointed to the key role of the intestinal barrier and the breakdown of these mechanisms in IBD. More and more scientists and clinicians are embracing the concept of the impaired intestinal epithelial barrier and its role in the pathogenesis and natural history of IBD. However, we are missing a key tool that bridges these scientific insights to clinical practice. Our goal is to overcome the limitations in understanding the molecular physiology of intestinal barrier function and develop a clinical tool to assess and quantify it. This review article explores the proteins in the intestinal tissue that are pivotal in regulating intestinal permeability. Understanding the molecular pathophysiology of impaired intestinal barrier function in IBD may lead to the development of a biochemical method of assessing intestinal tissue integrity which will have a significant impact on the development of novel therapies targeting the intestinal mucosa. Full article
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Open AccessArticle
Proteomics Analysis to Assess the Role of Mitochondria in BRCA1-Mediated Breast Tumorigenesis
Proteomes 2018, 6(2), 16; https://doi.org/10.3390/proteomes6020016 -
Abstract
Mitochondria are the organelles deputed to energy production, but they are also involved in carcinogenesis, cancer progression, and metastasis, playing a role in altered energy metabolism in cancer cells. Mitochondrial metabolism is connected with several mitochondrial pathways such as ROS signaling, Ca2+
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Mitochondria are the organelles deputed to energy production, but they are also involved in carcinogenesis, cancer progression, and metastasis, playing a role in altered energy metabolism in cancer cells. Mitochondrial metabolism is connected with several mitochondrial pathways such as ROS signaling, Ca2+ homeostasis, mitophagy, and mitochondrial biogenesis. These pathways are merged in an interactive super-network that seems to play a crucial role in cancer. Germline mutations of the BRCA1 gene account for 5–10% of breast cancers and confer a risk of developing the disease 10- to 20-fold much higher than in non-carriers. By considering metabolic networks that could reconcile both genetic and non-genetic causal mechanisms in BRCA1 driven tumorigenesis, we herein based our study on the hypothesis that BRCA1 haploinsufficiency might drive metabolic rewiring in breast epithelial cells, acting as a push toward malignant transformation. Using 2D-DIGE we analyzed and compared the mitochondrial proteomic profile of sporadic breast cancer cell line (MCF7) and BRCA1 mutated breast cancer cell line (HCC1937). Image analysis was carried out with Decider Software, and proteins differentially expressed were identified by LC-MS/MS on a quadrupole-orbitrap mass spectrometer Q-Exactive. Ingenuity pathways analysis software was used to analyze the fifty-three mitochondrial proteins whose expression resulted significantly altered in response to BRCA1 mutation status. Mitochondrial Dysfunction and oxidative phosphorylation, and energy production and nucleic acid metabolism were, respectively, the canonical pathway and the molecular function mainly affected. Western blotting analysis was done to validate the expression and the peculiar mitochondrial compartmentalization of specific proteins such us HSP60 and HIF-1α. Particularly intriguing is the correlation between BRCA1 mutation status and HIF-1α localization into the mitochondria in a BRCA1 dependent manner. Data obtained led us to hypothesize an interesting connection between BRCA1 and mitochondria pathways, capable to trigger metabolic changes, which, in turn, sustain the high energetic and anabolic requirements of the malignant phenotype. Full article
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Open AccessArticle
Association of Proteomics Changes with Al-Sensitive Root Zones in Switchgrass
Proteomes 2018, 6(2), 15; https://doi.org/10.3390/proteomes6020015 -
Abstract
In this paper, we report on aluminum (Al)-induced root proteomic changes in switchgrass. After growth in a hydroponic culture system supplemented with 400 μM of Al, plants began to show signs of physiological stress such as a reduction in photosynthetic rate. At this
[...] Read more.
In this paper, we report on aluminum (Al)-induced root proteomic changes in switchgrass. After growth in a hydroponic culture system supplemented with 400 μM of Al, plants began to show signs of physiological stress such as a reduction in photosynthetic rate. At this time, the basal 2-cm long root tips were harvested and divided into two segments, each of 1-cm in length, for protein extraction. Al-induced changes in proteomes were identified using tandem mass tags mass spectrometry (TMT-MS)-based quantitative proteomics analysis. A total of 216 proteins (approximately 3.6% of total proteins) showed significant differences between non-Al treated control and treated groups with significant fold change (twice the standard deviation; FDR adjusted p-value < 0.05). The apical root tip tissues expressed more dramatic proteome changes (164 significantly changed proteins; 3.9% of total proteins quantified) compared to the elongation/maturation zones (52 significantly changed proteins, 1.1% of total proteins quantified). Significantly changed proteins from the apical 1-cm root apex tissues were clustered into 25 biological pathways; proteins involved in the cell cycle (rotamase FKBP 1 isoforms, and CDC48 protein) were all at a reduced abundance level compared to the non-treated control group. In the root elongation/maturation zone tissues, the identified proteins were placed into 18 pathways, among which proteins involved in secondary metabolism (lignin biosynthesis) were identified. Several STRING protein interaction networks were developed for these Al-induced significantly changed proteins. This study has identified a large number of Al-responsive proteins, including transcription factors, which will be used for exploring new Al tolerance genes and mechanisms. Data are available via ProteomeXchange with identifiers PXD008882 and PXD009125. Full article
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Open AccessFeature PaperArticle
The Secretome and N-Glycosylation Profiles of the Charophycean Green Alga, Penium margaritaceum, Resemble Those of Embryophytes
Proteomes 2018, 6(2), 14; https://doi.org/10.3390/proteomes6020014 -
Abstract
The secretome can be defined as the population of proteins that are secreted into the extracellular environment. Many proteins that are secreted by eukaryotes are N-glycosylated. However, there are striking differences in the diversity and conservation of N-glycosylation patterns between taxa.
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The secretome can be defined as the population of proteins that are secreted into the extracellular environment. Many proteins that are secreted by eukaryotes are N-glycosylated. However, there are striking differences in the diversity and conservation of N-glycosylation patterns between taxa. For example, the secretome and N-glycosylation structures differ between land plants and chlorophyte green algae, but it is not clear when this divergence took place during plant evolution. A potentially valuable system to study this issue is provided by the charophycean green algae (CGA), which is the immediate ancestors of land plants. In this study, we used lectin affinity chromatography (LAC) coupled with mass spectrometry to characterize the secretome including secreted N-glycoproteins of Penium margaritaceum, which is a member of the CGA. The identified secreted proteins and N-glycans were compared to those known from the chlorophyte green alga Chlamydomonas reinhardtii and the model land plant, Arabidopsis thaliana, to establish their evolutionary context. Our approach allowed the identification of cell wall proteins and proteins modified with N-glycans that are identical to those of embryophytes, which suggests that the P. margaritaceum secretome is more closely related to those of land plants than to those of chlorophytes. The results of this study support the hypothesis that many of the proteins associated with plant cell wall modification as well as other extracellular processes evolved prior to the colonization of terrestrial habitats. Full article
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Open AccessFeature PaperReview
Subcellular Proteomics: Application to Elucidation of Flooding-Response Mechanisms in Soybean
Proteomes 2018, 6(1), 13; https://doi.org/10.3390/proteomes6010013 -
Abstract
Soybean, which is rich in protein and oil, is cultivated in several climatic zones; however, its growth is markedly decreased by flooding. Proteomics is a useful tool for understanding the flooding-response mechanism in soybean. Subcellular proteomics has the potential to elucidate localized cellular
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Soybean, which is rich in protein and oil, is cultivated in several climatic zones; however, its growth is markedly decreased by flooding. Proteomics is a useful tool for understanding the flooding-response mechanism in soybean. Subcellular proteomics has the potential to elucidate localized cellular responses and investigate communications among subcellular components during plant growth and during stress. Under flooding, proteins related to signaling, stress and the antioxidative system are increased in the plasma membrane; scavenging enzymes for reactive-oxygen species are suppressed in the cell wall; protein translation is suppressed through inhibition of proteins related to preribosome biogenesis and mRNA processing in the nucleus; levels of proteins involved in the electron transport chain are reduced in the mitochondrion; and levels of proteins related to protein folding are decreased in the endoplasmic reticulum. This review discusses the advantages of a gel-free/label-free proteomic technique and methods of plant subcellular purification. It also summarizes cellular events in soybean under flooding and discusses future prospects for generation of flooding-tolerant soybean. Full article
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Open AccessArticle
The Gene-Centric Content Management System and Its Application for Cognitive Proteomics
Proteomes 2018, 6(1), 12; https://doi.org/10.3390/proteomes6010012 -
Abstract
The Human Proteome Project is moving into the next phase of creating and/or reconsidering the functional annotations of proteins using the chromosome-centric paradigm. This challenge cannot be solved exclusively using automated means, but rather requires human intelligence for interpreting the combined data. To
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The Human Proteome Project is moving into the next phase of creating and/or reconsidering the functional annotations of proteins using the chromosome-centric paradigm. This challenge cannot be solved exclusively using automated means, but rather requires human intelligence for interpreting the combined data. To foster the integration between human cognition and post-genome array a number of specific tools were recently developed, among them CAPER, GenomewidePDB, and The Proteome Browser (TPB). For the purpose of tackling the task of protein functional annotating the Gene-Centric Content Management System (GenoCMS) was expanded with new features. The goal was to enable bioinformaticans to develop self-made applications and to position these applets within the generalized informational canvas supported by GenoCMS. We report the results of GenoCMS-enabled integration of the concordant informational flows in the chromosome-centric framework of the human chromosome 18 project. The workflow described in the article can be scaled to other human chromosomes, and also supplemented with new tracks created by the user. The GenoCMS is an example of a project-oriented informational system, which are important for public data sharing. Full article
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Open AccessFeature PaperArticle
Pilot Study on Mass Spectrometry–Based Analysis of the Proteome of CD34+CD123+ Progenitor Cells for the Identification of Potential Targets for Immunotherapy in Acute Myeloid Leukemia
Proteomes 2018, 6(1), 11; https://doi.org/10.3390/proteomes6010011 -
Abstract
Targeting of leukemic stem cells with specific immunotherapy would be an ideal approach for the treatment of myeloid malignancies, but suitable epitopes are unknown. The comparative proteome-level characterization of hematopoietic stem and progenitor cells from healthy stem cell donors and patients with acute
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Targeting of leukemic stem cells with specific immunotherapy would be an ideal approach for the treatment of myeloid malignancies, but suitable epitopes are unknown. The comparative proteome-level characterization of hematopoietic stem and progenitor cells from healthy stem cell donors and patients with acute myeloid leukemia has the potential to reveal differentially expressed proteins which can be used as surface-markers or as proxies for affected molecular pathways. We employed mass spectrometry methods to analyze the proteome of the cytosolic and the membrane fraction of CD34 and CD123 co-expressing FACS-sorted leukemic progenitors from five patients with acute myeloid leukemia. As a reference, CD34+CD123+ normal hematopoietic progenitor cells from five healthy, granulocyte-colony stimulating factor (G-CSF) mobilized stem cell donors were analyzed. In this Tandem Mass Tag (TMT) 10-plex labelling–based approach, 2070 proteins were identified with 171 proteins differentially abundant in one or both cellular compartments. This proof-of-principle-study demonstrates the potential of mass spectrometry to detect differentially expressed proteins in two compartment fractions of the entire proteome of leukemic stem cells, compared to their non-malignant counterparts. This may contribute to future immunotherapeutic target discoveries and individualized AML patient characterization. Full article
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Open AccessArticle
Revealing Subtle Functional Subgroups in Class A Scavenger Receptors by Pattern Discovery and Disentanglement of Aligned Pattern Clusters
Proteomes 2018, 6(1), 10; https://doi.org/10.3390/proteomes6010010 -
Abstract
A protein family has similar and diverse functions locally conserved as aligned sequence segments. Further discovering their association patterns could reveal subtle family subgroup characteristics. Since aligned residues associations (ARAs) in Aligned Pattern Clusters (APCs) are complex and intertwined due to entangled function,
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A protein family has similar and diverse functions locally conserved as aligned sequence segments. Further discovering their association patterns could reveal subtle family subgroup characteristics. Since aligned residues associations (ARAs) in Aligned Pattern Clusters (APCs) are complex and intertwined due to entangled function, factors, and variance in the source environment, we have recently developed a novel method: Aligned Residue Association Discovery and Disentanglement (ARADD) to solve this problem. ARADD first obtains from an APC an ARA Frequency Matrix and converts it to an adjusted statistical residual vectorspace (SRV). It then disentangles the SRV into Principal Components (PCs) and Re-projects their vectors to a SRV to reveal succinct orthogonal AR groups. In this study, we applied ARADD to class A scavenger receptors (SR-A), a subclass of a diverse protein family binding to modified lipoproteins with diverse biological functionalities not explicitly known. Our experimental results demonstrated that ARADD can unveil subtle subgroups in sequence segments with diverse functionality and highly variable sequence lengths. We also demonstrated that the ARAs captured in a Position Weight Matrix or an APC were entangled in biological function and domain location but disentangled by ARADD to reveal different subclasses without knowing their actual occurrence positions. Full article
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