scholarly journals ProMetIS, deep phenotyping of mouse models by combined proteomics and metabolomics analysis

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Alyssa Imbert ◽  
Magali Rompais ◽  
Mohammed Selloum ◽  
Florence Castelli ◽  
Emmanuelle Mouton-Barbosa ◽  
...  
Keyword(s):  
Mouse Models ◽  
Physiological Role ◽  
R Package ◽  
Level Data ◽  
Molecular Information ◽  
Number Of Individuals ◽  
Deep Phenotyping ◽  
Omics Data Integration

AbstractGenes are pleiotropic and getting a better knowledge of their function requires a comprehensive characterization of their mutants. Here, we generated multi-level data combining phenomic, proteomic and metabolomic acquisitions from plasma and liver tissues of two C57BL/6 N mouse models lacking the Lat (linker for activation of T cells) and the Mx2 (MX dynamin-like GTPase 2) genes, respectively. Our dataset consists of 9 assays (1 preclinical, 2 proteomics and 6 metabolomics) generated with a fully non-targeted and standardized approach. The data and processing code are publicly available in the ProMetIS R package to ensure accessibility, interoperability, and reusability. The dataset thus provides unique molecular information about the physiological role of the Lat and Mx2 genes. Furthermore, the protocols described herein can be easily extended to a larger number of individuals and tissues. Finally, this resource will be of great interest to develop new bioinformatic and biostatistic methods for multi-omics data integration.

scholarly journals GWENA: gene co-expression networks analysis and extended modules characterization in a single Bioconductor package

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Gwenaëlle G. Lemoine ◽  
Marie-Pier Scott-Boyer ◽  
Bathilde Ambroise ◽  
Olivier Périn ◽  
Arnaud Droit
Keyword(s):  
Muscle Development ◽  
R Package ◽  
Topological Information ◽  
Old Patients ◽  
Network Modules ◽  
Extended Analysis ◽  
Networks Analysis ◽  
Underlying Processes

Abstract Background Network-based analysis of gene expression through co-expression networks can be used to investigate modular relationships occurring between genes performing different biological functions. An extended description of each of the network modules is therefore a critical step to understand the underlying processes contributing to a disease or a phenotype. Biological integration, topology study and conditions comparison (e.g. wild vs mutant) are the main methods to do so, but to date no tool combines them all into a single pipeline. Results Here we present GWENA, a new R package that integrates gene co-expression network construction and whole characterization of the detected modules through gene set enrichment, phenotypic association, hub genes detection, topological metric computation, and differential co-expression. To demonstrate its performance, we applied GWENA on two skeletal muscle datasets from young and old patients of GTEx study. Remarkably, we prioritized a gene whose involvement was unknown in the muscle development and growth. Moreover, new insights on the variations in patterns of co-expression were identified. The known phenomena of connectivity loss associated with aging was found coupled to a global reorganization of the relationships leading to expression of known aging related functions. Conclusion GWENA is an R package available through Bioconductor (https://bioconductor.org/packages/release/bioc/html/GWENA.html) that has been developed to perform extended analysis of gene co-expression networks. Thanks to biological and topological information as well as differential co-expression, the package helps to dissect the role of genes relationships in diseases conditions or targeted phenotypes. GWENA goes beyond existing packages that perform co-expression analysis by including new tools to fully characterize modules, such as differential co-expression, additional enrichment databases, and network visualization.

scholarly journals Strictly co-isogenic C57BL/6J-Prnp−/− mice: A rigorous resource for prion science

2016 ◽  
Vol 213 (3) ◽  
pp. 313-327 ◽  
Author(s):  
Mario Nuvolone ◽  
Mario Hermann ◽  
Silvia Sorce ◽  
Giancarlo Russo ◽  
Cinzia Tiberi ◽  
...  
Keyword(s):  
Laboratory Mouse ◽  
Embryonic Stem ◽  
Physiological Role ◽  
Cellular Prion Protein ◽  
Transmissible Spongiform Encephalopathies ◽  
Phenotypic Characterization ◽  
Spongiform Encephalopathies ◽  
Demyelinating Peripheral Neuropathy

Although its involvement in prion replication and neurotoxicity during transmissible spongiform encephalopathies is undisputed, the physiological role of the cellular prion protein (PrPC) remains enigmatic. A plethora of functions have been ascribed to PrPC based on phenotypes of Prnp−/− mice. However, all currently available Prnp−/− lines were generated in embryonic stem cells from the 129 strain of the laboratory mouse and mostly crossed to non-129 strains. Therefore, Prnp-linked loci polymorphic between 129 and the backcrossing strain resulted in systematic genetic confounders and led to erroneous conclusions. We used TALEN-mediated genome editing in fertilized mouse oocytes to create the Zurich-3 (ZH3) Prnp-ablated allele on a pure C57BL/6J genetic background. Genomic, transcriptional, and phenotypic characterization of PrnpZH3/ZH3 mice failed to identify phenotypes previously described in non–co-isogenic Prnp−/− mice. However, aged PrnpZH3/ZH3 mice developed a chronic demyelinating peripheral neuropathy, confirming the crucial involvement of PrPC in peripheral myelin maintenance. This new line represents a rigorous genetic resource for studying the role of PrPC in physiology and disease.

scholarly journals Discovery and characterization of a novel family of prokaryotic nanocompartments involved in sulfur metabolism

2020 ◽  
Author(s):  
Robert J. Nichols ◽  
Benjamin LaFrance ◽  
Naiya R. Phillips ◽  
Luke M. Oltrogge ◽  
Luis E. Valentin-Alvarado ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Biochemical Characterization ◽  
Sulfur Metabolism ◽  
Physiological Role ◽  
Enzymatic Characterization ◽  
Cysteine Desulfurase ◽  
Future Studies ◽  
Pcc 7942

AbstractProkaryotic nanocompartments, also known as encapsulins, are a recently discovered proteinaceous organelle in prokaryotes that compartmentalize cargo enzymes. While initial studies have begun to elucidate the structure and physiological roles of encapsulins, bioinformatic evidence suggests that a great diversity of encapsulin nanocompartments remains unexplored. Here, we describe a novel encapsulin in the freshwater cyanobacterium Synechococcus elongatus PCC 7942. This nanocompartment is upregulated upon sulfate starvation and encapsulates a cysteine desulfurase enzyme via an N-terminal targeting sequence. Using cryoelectron microscopy, we have determined the structure of the nanocompartment complex to 2.2 Å resolution. Lastly, biochemical characterization of the complex demonstrated that the activity of the cysteine desulfurase is enhanced upon encapsulation. Taken together, our discovery, structural analysis, and enzymatic characterization of this prokaryotic nanocompartment provide a foundation for future studies seeking to understand the physiological role of this encapsulin in various bacteria.

scholarly journals Genetic Characterization of a Cell Envelope-Associated Proteinase from Lactobacillus helveticus CNRZ32

1999 ◽  
Vol 181 (15) ◽  
pp. 4592-4597 ◽  
Author(s):  
Jeffrey A. Pederson ◽  
Gerald J. Mileski ◽  
Bart C. Weimer ◽  
James L. Steele
Keyword(s):  
Cell Surface ◽  
Deletion Mutant ◽  
Cell Envelope ◽  
Physiological Role ◽  
Lactobacillus Helveticus ◽  
Whole Cells ◽  
A Cell ◽  
Hydrolysis Of

ABSTRACT A cell envelope-associated proteinase gene (prtH) was identified in Lactobacillus helveticus CNRZ32. TheprtH gene encodes a protein of 1,849 amino acids and with a predicted molecular mass of 204 kDa. The deduced amino acid sequence of the prtH product has significant identity (45%) to that of the lactococcal PrtP proteinases. Southern blot analysis indicates thatprtH is not broadly distributed within L. helveticus. A prtH deletion mutant of CNRZ32 was constructed to evaluate the physiological role of PrtH. PrtH is not required for rapid growth or fast acid production in milk by CNRZ32. Cell surface proteinase activity and specificity were determined by hydrolysis of αs1-casein fragment 1-23 by whole cells. A comparison of CNRZ32 and its prtH deletion mutant indicates that CNRZ32 has at least two cell surface proteinases that differ in substrate specificity.

Demonstration and characterization of motilin-binding sites in the rabbit cerebellum

1997 ◽  
Vol 272 (5) ◽  
pp. G994-G999 ◽  
Author(s):  
I. Depoortere ◽  
T. L. Peeters
Keyword(s):  
Binding Sites ◽  
Molecular Layer ◽  
Physiological Role ◽  
Scatchard Analysis ◽  
Affinity Binding ◽  
Lower Affinity ◽  
Erythromycin A ◽  
G Protein Coupled

This is the first report on central motilin receptors. Autoradiography on cerebellar slices revealed specific motilin-binding sites in the molecular layer of the cortex. Scatchard analysis of cold saturation studies showed the existence of a high-(pKd,hi = 9.07 +/- 0.09, where pKd is the negative logarithm of the dissociation constant) and a low-affinity binding site (pKd,lo = 6.56 +/- 0.09). Similar affinities were found with rabbit motilin and with the porcine (po) antagonist [Phe3, Leu13]po-motilin. Feline and canine motilin had a markedly lower affinity for the low-affinity site (pKd,lo = 5.29 and 4.58, respectively); chicken motilin had a lower affinity for both sites (pKd,hi = 8.36, pKd,lo = 3.97). Erythromycin A and its derivative N-trimethyl erythromycin A cnol ether also bound to cerebellar motilin receptors (pKd,hi = 7.29 and 8.91, respectively). Structure-activity studies with motilin fragments and the potency ranking of agonists suggest that a novel subtype receptor of motilin may exist in the brain. Guanosine 5'-O-(3-thiotriphosphate) (0.1 mM) reduced the number and the affinity for the high-affinity binding sites, which is evidence for G protein-coupled receptors. Our findings open new perspectives for the study of the physiological role of motilin.

scholarly journals Bringing radiomics into a multi-omics framework for a comprehensive genotype–phenotype characterization of oncological diseases

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Mario Zanfardino ◽  
Monica Franzese ◽  
Katia Pane ◽  
Carlo Cavaliere ◽  
Serena Monti ◽  
...  
Keyword(s):  
Data Integration ◽  
Data Structures ◽  
R Package ◽  
Biological Information ◽  
Phenotype Definition ◽  
Current State ◽  
Oncological Diseases ◽  
Cancer Phenotype

Abstract Genomic and radiomic data integration, namely radiogenomics, can provide meaningful knowledge in cancer diagnosis, prognosis and treatment. Despite several data structures based on multi-layer architecture proposed to combine multi-omic biological information, none of these has been designed and assessed to include radiomic data as well. To meet this need, we propose to use the MultiAssayExperiment (MAE), an R package that provides data structures and methods for manipulating and integrating multi-assay experiments, as a suitable tool to manage radiogenomic experiment data. To this aim, we first examine the role of radiogenomics in cancer phenotype definition, then the current state of radiogenomics data integration in public repository and, finally, challenges and limitations of including radiomics in MAE, designing an extended framework and showing its application on a case study from the TCGA-TCIA archives. Radiomic and genomic data from 91 patients have been successfully integrated in a single MAE object, demonstrating the suitability of the MAE data structure as container of radiogenomic data.

scholarly journals Mouse models of altered protein kinase A signaling

2009 ◽  
Vol 16 (3) ◽  
pp. 773-793 ◽  
Author(s):  
Lawrence S Kirschner ◽  
Zhirong Yin ◽  
Georgette N Jones ◽  
Emilia Mahoney
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Mouse Models ◽  
Physiological Role ◽  
Gene Families ◽  
Current Data ◽  
Model Organisms ◽  
Signaling System ◽  
Kinase A

Protein kinase A (PKA) is an evolutionarily conserved protein which has been studied in model organisms from yeast to man. Although the cAMP–PKA signaling system was the first mammalian second messenger system to be characterized, many aspects of this pathway are still not well understood. Owing to findings over the past decade implicating PKA signaling in endocrine (and other) tumorigenesis, there has been renewed interest in understanding the role of this pathway in physiology, particularly as it pertains to the endocrine system. Because of the availability of genetic tools, mouse modeling has become the pre-eminent system for studying the physiological role of specific genes and gene families as a means to understanding their relationship to human diseases. In this review, we will summarize the current data regarding mouse models that have targeted the PKA signaling system. These data have led to a better understanding of both the complexity and the subtlety of PKA signaling, and point the way for future studies, which may help to modulate this pathway for therapeutic effect.

scholarly journals Production and Characterization of a Thermostable Alcohol Dehydrogenase That Belongs to the Aldo-Keto Reductase Superfamily

2006 ◽  
Vol 72 (1) ◽  
pp. 233-238 ◽  
Author(s):  
Ronnie Machielsen ◽  
Agustinus R. Uria ◽  
Servé W. M. Kengen ◽  
John van der Oost
Keyword(s):  
Alcohol Dehydrogenase ◽  
Pyrococcus Furiosus ◽  
Enantiomeric Excess ◽  
Physiological Role ◽  
Secondary Alcohols ◽  
Gene Encoding ◽  
Ph Optimum ◽  
Reduction Of Ketones

ABSTRACT The gene encoding a novel alcohol dehydrogenase that belongs to the aldo-keto reductase superfamily has been identified in the hyperthermophilic archaeon Pyrococcus furiosus. The gene, referred to as adhD, was functionally expressed in Escherichia coli and subsequently purified to homogeneity. The enzyme has a monomeric conformation with a molecular mass of 32 kDa. The catalytic activity of the enzyme increases up to 100°C, and a half-life value of 130 min at this temperature indicates its high thermostability. AdhD exhibits a broad substrate specificity with, in general, a preference for the reduction of ketones (pH optimum, 6.1) and the oxidation of secondary alcohols (pH optimum, 8.8). Maximal specific activities were detected with 2,3-butanediol (108.3 U/mg) and diacetyl-acetoin (22.5 U/mg) in the oxidative and reductive reactions, respectively. Gas chromatrography analysis indicated that AdhD produced mainly (S)-2-pentanol (enantiomeric excess, 89%) when 2-pentanone was used as substrate. The physiological role of AdhD is discussed.

scholarly journals Characterization of ApuB, an Extracellular Type II Amylopullulanase from Bifidobacterium breve UCC2003

2008 ◽  
Vol 74 (20) ◽  
pp. 6271-6279 ◽  
Author(s):  
Mary O'Connell Motherway ◽  
Gerald F. Fitzgerald ◽  
Sabine Neirynck ◽  
Sinead Ryan ◽  
Lothar Steidler ◽  
...  
Keyword(s):  
Energy Source ◽  
Physiological Role ◽  
Class Ii ◽  
Type Ii ◽  
Starch Metabolism ◽  
Bifidobacterium Breve ◽  
Knockout Mutation

ABSTRACT The apuB gene of Bifidobacterium breve UCC2003 was shown to encode an extracellular amylopullulanase. ApuB is composed of a distinct N-terminally located α-amylase-containing domain which hydrolyzes α-1,4-glucosidic linkages in starch and related polysaccharides and a C-terminally located pullulanase-containing domain which hydrolyzes α-1,6 linkages in pullulan, allowing the classification of this enzyme as a bifunctional class II pullulanase. A knockout mutation of the apuB gene in B. breve UCC2003 rendered the resulting mutant incapable of growth in medium containing starch, amylopectin, glycogen, or pullulan as the sole carbon and energy source, confirming the crucial physiological role of this gene in starch metabolism.

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