scholarly journals Proteomics Dissection of Cardiac Protein Profiles of Humans and Model Organisms

2020 ◽  
Author(s):  
Nora Linscheid ◽  
Alberto Santos ◽  
Pi Camilla Poulsen ◽  
Robert W. Mills ◽  
Christian Stolte ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Global Analysis ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Treatment Strategies ◽  
Model Organism ◽  
Model Organisms ◽  
Protein Profiles ◽  
Novel Treatment Strategies ◽  
The Right ◽  
Protein Expression Profiles

AbstractThe study of human cardiac pathologies often relies on research conducted in model organisms to gain molecular insight into disease and to develop novel treatment strategies; however, translating findings from model organisms back to human can present a significant challenge, in part due to a lack of knowledge about the differences across species in cardiac protein abundances and their interactions. Here we set out to bridge this knowledge gap by presenting a global analysis of cardiac protein expression profiles in humans and commonly used model organisms. Using quantitative mass spectrometry-based proteomics, we measured the abundance of ~7,000 proteins in samples from the separate chambers of human, pig, horse, rat, mouse and zebrafish hearts. This knowledgebase of cardiac protein signatures is accessible through an online database at: atlas.cardiacproteomics.com. Quantitative comparison of the protein profiles support the pig as model organism of choice for arrhythmogenic right ventricular cardiomyopathy whereas comparison of profiles from the two-chambered zebrafish heart suggests a better resemblance to the right side of mammalian hearts. This proteomics resource facilitates translational prospect of cardiac studies from model organisms to humans by enabling direct comparison of disease-linked protein networks across species.

scholarly journals CRISPR/Cas9-engineered Drosophila knock-in models to study VCP diseases

2021 ◽  
Author(s):  
Jordan M. Wall ◽  
Ankita Basu ◽  
Elizabeth R.M. Zunica ◽  
Olga S. Dubuisson ◽  
Kathryn Pergola ◽  
...  
Keyword(s):  
Treatment Options ◽  
Treatment Strategies ◽  
Model Organism ◽  
Organelle Biogenesis ◽  
Protein Aggregate ◽  
Phenotypic Differences ◽  
Aaa Atpase ◽  
Novel Treatment Strategies ◽  
Unexpected Findings

Valosin containing protein (VCP) is a hexameric type II AAA ATPase required for several cellular processes including ER-associated degradation, organelle biogenesis, autophagy and membrane fusion. VCP contains three domains: a regulatory N-terminal domain and two ATPase domains (D1 and D2). Mutations in the N-terminal and D1 domains are associated with several degenerative diseases, including Multisystem Proteinopathy (MSP-1) and ALS. However, patients with VCP mutations vary widely in their pathology and clinical penetrance, making it difficult to devise effective treatment strategies. Having a deeper understanding of how each mutation affects VCP function could enhance the prediction of clinical outcomes and design of personalized treatment options. Over-expressing VCP patient mutations in Drosophila has been shown to mimic many pathologies observed in human patients. The power of a genetically tractable model organism coupled with well-established in vivo assays and a relatively short life cycle make Drosophila an attractive system to study VCP disease pathogenesis and novel treatment strategies. Using CRISPR/Cas9, we have generated individual Drosophila knock-in mutants that include nine hereditary VCP disease mutations. We validate that these models display many hallmarks of VCP-mediated degeneration, including progressive decline in mobility, protein aggregate accumulation and defects in lysosomal and mitochondrial function. We also made some novel and unexpected findings, including laminopathies and sex-specific phenotypic differences in several mutants. Taken together, the Drosophila VCP disease models we have generated in this study will be useful for studying the etiology of individual VCP patient mutations and for testing potential genetic and/or pharmacological therapies.

scholarly journals Interactions Screenings Unearth Potential New Divisome Components in the Chlamydia-Related Bacterium, Waddlia chondrophila

2019 ◽  
Vol 7 (12) ◽  
pp. 617
Author(s):  
Firuza Bayramova ◽  
Nicolas Jacquier ◽  
Gilbert Greub
Keyword(s):  
Iron Homeostasis ◽  
Expression Profiles ◽  
Model Organism ◽  
E Coli ◽  
Obligate Intracellular ◽  
Gene And Protein Expression ◽  
Related Bacterium ◽  
Obligate Intracellular Bacteria ◽  
Protein Expression Profiles ◽  
Two Hybrid

Chlamydiales order members are obligate intracellular bacteria, dividing by binary fission. However, Chlamydiales lack the otherwise conserved homologue of the bacterial division organizer FtsZ and certain division protein homologues. FtsZ might be functionally replaced in Chlamydiales by the actin homologue MreB. RodZ, the membrane anchor of MreB, localizes early at the division septum. In order to better characterize the organization of the chlamydial divisome, we performed co-immunoprecipitations and yeast-two hybrid assays to study the interactome of RodZ, using Waddlia chondrophila, a potentially pathogenic Chlamydia-related bacterium, as a model organism. Three potential interactors were further investigated: SecA, FtsH, and SufD. The gene and protein expression profiles of these three genes were measured and are comparable with recently described division proteins. Moreover, SecA, FtsH, and SufD all showed a peripheral localization, consistent with putative inner membrane localization and interaction with RodZ. Notably, heterologous overexpression of the abovementioned proteins could not complement E. coli mutants, indicating that these proteins might play different functions in these two bacteria or that important regulators are not conserved. Altogether, this study brings new insights to the composition of the chlamydial divisome and points to links between protein secretion, degradation, iron homeostasis, and chlamydial division.

scholarly journals PIC-Me: paralogs and isoforms classifier based on machine-learning approaches

2021 ◽  
Vol 22 (S11) ◽  
Author(s):  
Jooseong Oh ◽  
Sung-Gwon Lee ◽  
Chungoo Park
Keyword(s):  
Machine Learning ◽  
Large Scale ◽  
Gene Annotation ◽  
Sequence Similarity ◽  
Global Analysis ◽  
Model Organism ◽  
Model Organisms ◽  
Support Vector ◽  
Learning Approaches ◽  
Rna Seq

Abstract Background Paralogs formed through gene duplication and isoforms formed through alternative splicing have been important processes for increasing protein diversity and maintaining cellular homeostasis. Despite their recognized importance and the advent of large-scale genomic and transcriptomic analyses, paradoxically, accurate annotations of all gene loci to allow the identification of paralogs and isoforms remain surprisingly incomplete. In particular, the global analysis of the transcriptome of a non-model organism for which there is no reference genome is especially challenging. Results To reliably discriminate between the paralogs and isoforms in RNA-seq data, we redefined the pre-existing sequence features (sequence similarity, inverse count of consecutive identical or non-identical blocks, and match-mismatch fraction) previously derived from full-length cDNAs and EST sequences and described newly discovered genomic and transcriptomic features (twilight zone of protein sequence alignment and expression level difference). In addition, the effectiveness and relevance of the proposed features were verified with two widely used support vector machine (SVM) and random forest (RF) models. From nine RNA-seq datasets, all AUC (area under the curve) scores of ROC (receiver operating characteristic) curves were over 0.9 in the RF model and significantly higher than those in the SVM model. Conclusions In this study, using an RF model with five proposed RNA-seq features, we implemented our method called Paralogs and Isoforms Classifier based on Machine-learning approaches (PIC-Me) and showed that it outperformed an existing method. Finally, we envision that our tool will be a valuable computational resource for the genomics community to help with gene annotation and will aid in comparative transcriptomics and evolutionary genomics studies, especially those on non-model organisms.

scholarly journals Tabula Microcebus: A transcriptomic cell atlas of mouse lemur, an emerging primate model organism

2021 ◽  
Author(s):  
◽  
Camille Ezran ◽  
Shixuan Liu ◽  
Stephen Chang ◽  
Jingsi Ming ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Model Organism ◽  
Cell Types ◽  
The Body ◽  
Mouse Lemur ◽  
Human Model ◽  
Model Organisms ◽  
Cell Type ◽  
Primate Model ◽  
Primate Cell

Mouse lemurs are the smallest, fastest reproducing, and among the most abundant primates, and an emerging model organism for primate biology, behavior, health and conservation. Although much has been learned about their physiology and their Madagascar ecology and phylogeny, little is known about their cellular and molecular biology. Here we used droplet- and plate-based single cell RNA-sequencing to profile 226,000 cells from 27 mouse lemur organs and tissues opportunistically procured from four donors clinically and histologically characterized. Using computational cell clustering, integration, and expert cell annotation, we defined and biologically organized over 750 mouse lemur molecular cell types and their full gene expression profiles. These include cognates of most classical human cell types, including stem and progenitor cells, and the developmental programs for spermatogenesis, hematopoiesis, and other adult tissues. We also described dozens of previously unidentified or sparsely characterized cell types and subtypes. We globally compared cell type expression profiles to define the molecular relationships of cell types across the body, and explored primate cell type evolution by comparing mouse lemur cell profiles to those of the homologous cells in human and mouse. This revealed cell type specific patterns of primate cell specialization even within a single tissue compartment, as well as many cell types for which lemur provides a better human model than mouse. The atlas provides a cellular and molecular foundation for studying this primate model organism, and establishes a general approach for other emerging model organisms.

scholarly journals A Brief Analysis of Proteomic Profile Changes during Zebrafish Regeneration

Biomolecules ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 35
Author(s):  
Zulvikar Syambani Ulhaq ◽  
William Ka Fai Tse
Keyword(s):  
Cell Cycle Control ◽  
Treatment Strategies ◽  
Model Organism ◽  
Target Proteins ◽  
Biological Studies ◽  
Profile Changes ◽  
Proteome Profile ◽  
Novel Treatment Strategies ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

Unlike mammals, zebrafish are capable to regenerate many of their organs, however, the response of tissue damage varies across tissues. Understanding the molecular mechanism behind the robust regenerative capacity in a model organism may help to identify and develop novel treatment strategies for mammals (including humans). Hence, we systematically analyzed the current literature on the proteome profile collected from different regenerated zebrafish tissues. Our analyses underlining that several proteins and protein families responsible as a component of cytoskeleton and structure, protein synthesis and degradation, cell cycle control, and energy metabolism were frequently identified. Moreover, target proteins responsible for the initiation of the regeneration process, such as inflammation and immune response were less frequently detected. This highlights the limitation of previous proteomic analysis and suggested a more sensitive modern proteomics analysis is needed to unfold the mechanism. This brief report provides a list of target proteins with predicted functions that could be useful for further biological studies.

scholarly journals Network integration of multi-tumour omics data suggests novel targeting strategies

2017 ◽  
Author(s):  
Ítalo Faria do Valle ◽  
Giulia Menichetti ◽  
Giorgia Simonetti ◽  
Samantha Bruno ◽  
Isabella Zironi ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Drug Targets ◽  
Expression Profiles ◽  
Treatment Strategies ◽  
Gene Expression Profiles ◽  
Drug Repurposing ◽  
Ubiquitin Proteasome System ◽  
The Cancer Genome Atlas ◽  
Novel Treatment Strategies

AbstractWe characterize different tumour types in the search for multi-tumour drug targets, in particular aiming for drug repurposing or novel drug combinations. Starting from 11 tumour types from The Cancer Genome Atlas, we obtain three clusters based on transcriptomic correlation profiles. A network-based analysis, integrating gene expression profiles and protein interactions of cancer-related genes, allowed us to define three cluster-specific signatures, with genes belonging to NF-ĸB signaling, chromosomal instability, ubiquitin-proteasome system, DNA metabolism, and apoptosis biological processes. These signatures have been characterized by different approaches based on mutational, pharmacological and clinical evidences, demonstrating the validity of our selection. Moreover, we defined new pharmacological strategies validated by in vitro experiments that showed inhibition of cell growth in two tumour cell lines, with significant synergistic effect. Our study thus provides a list of genes and pathways with the potential to be used, singularly or in combination, for the design of novel treatment strategies.

Proteome alteration of soybean as a function of pod distortion syndrome

2017 ◽  
Author(s):  
Kamal Payghamzadeh ◽  
Mahmood Toorchi ◽  
Zahra Sadat Shobbar
Keyword(s):  
Signal Transduction ◽  
Energy Production ◽  
Expression Profiles ◽  
Large Subunit ◽  
Alpha Subunit ◽  
Protein Profiles ◽  
Soybean Plants ◽  
Protein Expression Profiles ◽  
Oxygen Evolving ◽  
And Storage

Pod distortion syndrome (PDS) is a particular type of growth in which soybean plants remain green long after pod maturation. The aim of this study was to assess protein profiles of PDS and non-PDS soybeans via proteomics approaches. Therefore, protein expression profiles of PDS and non-PDS soybean cultivars viz. Katul and Gorgan 3 were analyzed by nESI-LC-MS/MS. Comparative analysis of significant proteins via nESI-LC-MS/MS revealed that 5 and 11 proteins in Gorgan 3 had significantly different expression levels in PDS and non-PDS, respectively. Most of these proteins had already been known to regulate diverse cellular activities e.g. energy production, metabolism, signal transduction, gene transcription and translation as well as protein destination and storage. But, the present findings suggest that the key regulators of PDS in soybean plants may be are 14-3-3 like protein, Nascent Polypeptide-Associated Complex Alpha Subunit, Rubisco large subunit, and oxygen evolving enhancer protein 2 protein.

scholarly journals Expression Profile of Genes Encoding Proteins Involved in Regulation of Vasculature Development and Heart Muscle Morphogenesis—A Transcriptomic Approach Based on a Porcine Model

2021 ◽  
Vol 22 (16) ◽  
pp. 8794
Author(s):  
Mariusz J. Nawrocki ◽  
Karol Jopek ◽  
Maciej Zdun ◽  
Paul Mozdziak ◽  
Marek Jemielity ◽  
...  
Keyword(s):  
Heart Muscle ◽  
Cultured Cells ◽  
Expression Profiles ◽  
Treatment Strategies ◽  
Coronary Vessels ◽  
Atrial Appendage ◽  
Right Atrial ◽  
Reduced Ejection Fraction ◽  
Right Atrial Appendage ◽  
The Right

Despite significant advances in treatment of acute coronary syndromes (ACS) many subjects still develop heart failure due to significantly reduced ejection fraction. Currently, there are no commonly available treatment strategies that replace the infarcted/dysfunctional myocardium. Therefore, understanding the mechanisms that control the regeneration of the heart muscle is important. The development of new coronary vessels plays a pivotal role in cardiac regeneration. Employing microarray expression assays and RT-qPCR validation expression pattern of genes in long-term primary cultured cells isolated form the right atrial appendage (RAA) and right atrium (RA) was evaluated. After using DAVID software, it indicated the analysis expression profiles of genes involved in ontological groups such as: “angiogenesis”, “blood vessel morphogenesis”, “circulatory system development”, “regulation of vasculature development”, and “vasculature development” associated with the process of creation new blood vessels. The performed transcriptomic comparative analysis between two different compartments of the heart muscle allowed us to indicate the presence of differences in the expression of key transcripts depending on the cell source. Increases in culture intervals significantly increased expression of SFRP2, PRRX1 genes and some other genes involved in inflammatory process, such as: CCL2, IL6, and ROBO1. Moreover, the right atrial appendage gene encoding lysyl oxidase (LOX) showed much higher expression compared to the pre-cultivation state.

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