Disease pathways at the Rat Genome Database Pathway Portal: genes in context-a network approach to understanding the molecular mechanisms of disease

Over the last 30 years the role of monoclonal antibodies in therapeutics has increased enormously, revolutionizing treatment in most medical specialties, including neurology. Monoclonal antibodies are key therapeutic agents for several neurological conditions with diverse pathophysiological mechanisms, including multiple sclerosis, migraines and neuromuscular disease. In addition, a great number of monoclonal antibodies against several targets are being investigated for many more neurological diseases, which reflects our advances in understanding the pathogenesis of these diseases. Untangling the molecular mechanisms of disease allows monoclonal antibodies to block disease pathways accurately and efficiently with exceptional target specificity, minimizing non-specific effects. On the other hand, accumulating experience shows that monoclonal antibodies may carry class-specific and target-associated risks. This article provides an overview of different types of monoclonal antibodies and their characteristics and reviews monoclonal antibodies currently in use or under development for neurological disease.

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The Fibrillins and Key Molecular Mechanisms that Initiate Disease Pathways

Marfan Syndrome: A Primer for Clinicians and Scientists ◽

10.1007/978-1-4419-9013-6_15 ◽

2004 ◽

pp. 178-187

Author(s):

Lynn Y. Sakai

Keyword(s):

Molecular Mechanisms ◽

Disease Pathways

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The Respiratory Disease Portal At The Rat Genome Database: A Genomic Resource For Asthma, COPD, And Other Respiratory Diseases

10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a1937 ◽

2012 ◽

Author(s):

Melinda Dwinell ◽

Stan Laulederkind ◽

Tom Hayman ◽

Timothy Lowry ◽

Rajni Nigam ◽

...

Keyword(s):

Respiratory Disease ◽

Respiratory Diseases ◽

Genome Database ◽

Genomic Resource ◽

Rat Genome

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The Rat Genome Database 2013--data, tools and users

Briefings in Bioinformatics ◽

10.1093/bib/bbt007 ◽

2013 ◽

Vol 14 (4) ◽

pp. 520-526 ◽

Cited By ~ 57

Author(s):

S. J. F. Laulederkind ◽

G. T. Hayman ◽

S.-J. Wang ◽

J. R. Smith ◽

T. F. Lowry ◽

...

Keyword(s):

Genome Database ◽

Rat Genome

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PhenoMiner: quantitative phenotype curation at the rat genome database

Database ◽

10.1093/database/bat015 ◽

2013 ◽

Vol 2013 ◽

Cited By ~ 20

Author(s):

Stanley J F Laulederkind ◽

Weisong Liu ◽

Jennifer R Smith ◽

G Thomas Hayman ◽

Shur-Jen Wang ◽

...

Keyword(s):

Biological Information ◽

Ontology Development ◽

Rat Strains ◽

Genome Database ◽

Quantitative Phenotype ◽

Phenotype Data ◽

Disease Associations ◽

Data Objects ◽

Cellular Components ◽

Rat Genome

Abstract The Rat Genome Database (RGD) is the premier repository of rat genomic and genetic data and currently houses >40 000 rat gene records as well as human and mouse orthologs, >2000 rat and 1900 human quantitative trait loci (QTLs) records and >2900 rat strain records. Biological information curated for these data objects includes disease associations, phenotypes, pathways, molecular functions, biological processes and cellular components. Recently, a project was initiated at RGD to incorporate quantitative phenotype data for rat strains, in addition to the currently existing qualitative phenotype data for rat strains, QTLs and genes. A specialized curation tool was designed to generate manual annotations with up to six different ontologies/vocabularies used simultaneously to describe a single experimental value from the literature. Concurrently, three of those ontologies needed extensive addition of new terms to move the curation forward. The curation interface development, as well as ontology development, was an ongoing process during the early stages of the PhenoMiner curation project. Database URL: http://rgd.mcw.edu

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Using exosomal miRNAs extracted from follicular fluid to investigate their role in porcine oocyte development

10.21203/rs.3.rs-45890/v1 ◽

2020 ◽

Author(s):

Junhe Hu ◽

Jinyi Dong ◽

Zhi Zeng ◽

Juan Wu ◽

Xiansheng Tan ◽

...

Keyword(s):

Oocyte Maturation ◽

Follicular Fluid ◽

Molecular Mechanisms ◽

Target Genes ◽

Oocyte Development ◽

Clustering Methods ◽

Sequencing Data ◽

Genome Database ◽

Exosomal Mirnas ◽

Porcine Oocyte

Abstract Follicular development is crucial to normal oocyte maturation, with follicular size closely related to oocyte maturation. To better understand the molecular mechanisms behind porcine oocyte maturation, we obtained exosomal miRNA from porcine follicular fluid (PFF). These miRNA samples were then sequenced and analyzed regarding their different follicular sizes, as described in the methods section. First, these results showed that this process successfully isolated PFF exosomes. Nearly all valid reads from the PFF exosomal sequencing data were successfully mapped to the porcine genome database. Second, we used hierarchical clustering methods to determine that significantly expressed miRNAs were clustered into A, B, C, and D groups in our heatmap according to different follicle sizes. These results allowed for the targeting of potential mRNAs genes related to porcine oocyte development. Third, we chose ten, significantly expressed miRNAs and predicted their target genes for further GO analysis. These results showed that the expression levels of neurotransmitter secretion genes were greatly changed, as were many target genes involved in the regulation of FSH secretion. Notably, these are genes that are very closely related to oocyte maturation in growing follicles. We then used pathway analysis for these targeted genes based on the originally selected ten miRNAs. Results indicated that the pathways were mainly related to the biosynthesis of TGF-beta and its signaling pathway, which are very closely related to reproductive system functions. Finally, these exosomal miRNAs obtained from PFF may provide a valuable addition to our understanding of the mechanism of porcine oocyte maturation. It is also likely that these exosomal miRNAs could function as molecular biomarkers to choose high-quality oocytes and allow for in vitro porcine embryo production.

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Discovery of Diagnostic and Therapeutic Targets For Vascular Injury Induced By Methylglyoxal Using Proteomics

10.21203/rs.3.rs-453632/v1 ◽

2021 ◽

Author(s):

Ming-Zhang Xie ◽

Yan-Ting Liu ◽

Min Zhang ◽

Meng-Meng Zhao ◽

Ke-Tao Sun ◽

...

Keyword(s):

Vascular Injury ◽

Molecular Mechanisms ◽

Therapeutic Targets ◽

Reaction Monitoring ◽

New Disease ◽

Parallel Reaction ◽

Parallel Reaction Monitoring ◽

Colorimetric Assays ◽

Quantitative Fluorescence ◽

Disease Pathways

Abstract Background: Methylglyoxal, a byproduct of diabetes or the consumption of a high-carbohydrate diet, is associated with vascular injury; however, its molecular mechanisms remain unclear. We aimed to systematically characterize molecular profiles and offer unique insights into new disease pathways, thereby contributing to understanding the mechanisms and pathogenesis of vascular injury-related cardiovascular diseases. Methods: Cell survival assays were performed to assess DNA damage; oxidative stress was confirmed by colorimetric assays and quantitative fluorescence, and cyclooxygenase-2 and the mitogen-activated protein kinase pathways were assessed using ELISA. Differentially expressed proteins were quantitated via TMT-based LC-MS/MS and bioinformatics analysis, and confirmed by parallel reaction monitoring. Results: Vascular injury was assessed through colorimetric assays, quantitative fluorescence, ELISA, and survival assays. Of the 4029 proteins identified, 368 were differentially expressed after methylglyoxal treatment, compared with the negative control; 31 were defined as biomarkers or therapeutic targets according to the Gene Ontology Program, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction network analyses. Sixteen proteins were significantly (p<0.05) upregulated (>1.5-fold change) and 15 were dramatically downregulated (<0.667-fold change) and confirmed through parallel reaction monitoring.Conclusions: The 31 proteins identified as biomarkers or therapeutic targets may contribute to vascular dysfunction through DNA damage, oxidative stress, inflammation, autophagy, hypertension, endothelial dysfunction, vascular remodeling, and the coagulation cascade. Additionally, new disease pathways involving the Wnt, ErBb, and BMP signaling pathways were identified; all provide scope as potential underlying molecular mechanisms. Therefore, the 31 proteins identified warrant further development as new therapeutic or diagnostic targets for vascular diseases.

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Using exosomal miRNAs extracted from porcine follicular fluid to investigate their role in oocyte development

BMC Veterinary Research ◽

10.1186/s12917-020-02711-x ◽

2020 ◽

Vol 16 (1) ◽

Author(s):

Junhe Hu ◽

Jinyi Dong ◽

Zhi Zeng ◽

Juan Wu ◽

Xiansheng Tan ◽

...

Keyword(s):

Oocyte Maturation ◽

Follicular Fluid ◽

Molecular Mechanisms ◽

Target Genes ◽

Oocyte Development ◽

Clustering Methods ◽

Sequencing Data ◽

Genome Database ◽

Exosomal Mirnas ◽

Porcine Oocyte

Abstracts Background Follicular development is crucial to normal oocyte maturation, with follicular size closely related to oocyte maturation. To better understand the molecular mechanisms behind porcine oocyte maturation, we obtained exosomal miRNA from porcine follicular fluid (PFF). These miRNA samples were then sequenced and analyzed regarding their different follicular sizes, as described in the methods section. Results First, these results showed that this process successfully isolated PFF exosomes. Nearly all valid reads from the PFF exosomal sequencing data were successfully mapped to the porcine genome database. Second, we used hierarchical clustering methods to determine that significantly expressed miRNAs were clustered into A, B, C, and D groups in our heatmap according to different follicle sizes. These results allowed for the targeting of potential mRNAs genes related to porcine oocyte development. Third, we chose ten, significantly expressed miRNAs and predicted their target genes for further GO analysis. These results showed that the expression levels of neurotransmitter secretion genes were greatly changed, as were many target genes involved in the regulation of FSH secretion. Notably, these are genes that are very closely related to oocyte maturation in growing follicles. We then used pathway analysis for these targeted genes based on the originally selected ten miRNAs. Results indicated that the pathways were mainly related to the biosynthesis of TGF-beta and its signaling pathway, which are very closely related to reproductive system functions. Conclusions Finally, these exosomal miRNAs obtained from PFF may provide a valuable addition to our understanding of the mechanism of porcine oocyte maturation. It is also likely that these exosomal miRNAs could function as molecular biomarkers to choose high-quality oocytes and allow for in vitro porcine embryo production.

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Tools and strategies for physiological genomics: the Rat Genome Database

Physiological Genomics ◽

10.1152/physiolgenomics.00040.2005 ◽

2005 ◽

Vol 23 (2) ◽

pp. 246-256 ◽

Cited By ~ 21

Author(s):

Simon N. Twigger ◽

Dean Pasko ◽

Jeff Nie ◽

Mary Shimoyama ◽

Susan Bromberg ◽

...

Keyword(s):

Comparative Genomics ◽

Computational Biology ◽

Computational Techniques ◽

Genome Database ◽

Computational Tools ◽

Functional Roles ◽

Genomics Research ◽

Human And Mouse ◽

Rat Genome

The broad goal of physiological genomics research is to link genes to their functions using appropriate experimental and computational techniques. Modern genomics experiments enable the generation of vast quantities of data, and interpretation of this data requires the integration of information derived from many diverse sources. Computational biology and bioinformatics offer the ability to manage and channel this information torrent. The Rat Genome Database (RGD; http://rgd.mcw.edu ) has developed computational tools and strategies specifically supporting the goal of linking genes to their functional roles in rat and, using comparative genomics, to human and mouse. We present an overview of the database with a focus on these unique computational tools and describe strategies for the use of these resources in the area of physiological genomics.

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