scholarly journals WormPaths: Caenorhabditis elegans metabolic pathway annotation and visualization

2020 ◽  
Author(s):  
Melissa D. Walker ◽  
Gabrielle E. Giese ◽  
Amy D. Holdorf ◽  
Sushila Bhattacharya ◽  
Cédric Diot ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Metabolic Pathway ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
The Novel ◽  
C Elegans ◽  
Therapeutic Drugs ◽  
Metabolic Genes ◽  
Pathway Annotation ◽  
Road Maps

AbstractIn our group, we aim to understand metabolism in the nematode Caenorhabditis elegans and its relationships with gene expression, physiology and the response to therapeutic drugs. On March 15, 2020, a stay-at-home order was put into effect in the state of Massachusetts, USA, to flatten the curve of the spread of the novel SARS-CoV2 virus that causes COVID-19. For biomedical researchers in our state, this meant putting a hold on experiments for nine weeks until May 18, 2020. To keep the lab engaged and productive, and to enhance communication and collaboration, we embarked on an in-lab project that we all found important but that we never had the time for: the detailed annotation and drawing of C. elegans metabolic pathways. As a result, we present WormPaths, which is composed of two parts: 1) the careful manual annotation of metabolic genes into pathways, categories and levels, and 2) 66 pathway maps that include metabolites, metabolite structures, genes, reactions, and pathway connections between maps. These maps are available on our WormFlux website. We show that WormPaths provides easy-to-navigate maps and that the different levels in WormPaths can be used for metabolic pathway enrichment analysis of transcriptomic data. In the unfortunate event of additional lockdowns, we envision further developing these maps to be more interactive, with an analogy of road maps that are available on mobile devices.

scholarly journals WormPaths: Caenorhabditis elegans metabolic pathway annotation and visualization

Genetics ◽  
2021 ◽  
Author(s):  
Melissa D Walker ◽  
Gabrielle E Giese ◽  
Amy D Holdorf ◽  
Sushila Bhattacharya ◽  
Cédric Diot ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Metabolic Pathway ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
C Elegans ◽  
Therapeutic Drugs ◽  
Metabolic Genes ◽  
Pathway Annotation ◽  
Road Maps ◽  
Different Levels

Abstract In our group, we aim to understand metabolism in the nematode Caenorhabditis elegans and its relationships with gene expression, physiology and the response to therapeutic drugs. Visualization of the metabolic pathways that comprise the metabolic network is extremely useful for interpreting a wide variety of experiments. Detailed annotated metabolic pathway maps for C. elegans is mostly limited to pan-organismal maps, many with incomplete or inaccurate pathway and enzyme annotations. Here we present WormPaths, which is composed of two parts: 1) the careful manual annotation of metabolic genes into pathways, categories and levels, and 2) 62 pathway maps that include metabolites, metabolite structures, genes, reactions, and pathway connections between maps. These maps are available on the WormFlux website. We show that WormPaths provides easy-to-navigate maps and that the different levels in WormPaths can be used for metabolic pathway enrichment analysis of transcriptomic data. In the future we envision further developing these maps to be more interactive, with an analogy of road maps that are available on mobile devices.

scholarly journals Functional Redundancy of the B9 Proteins and Nephrocystins in Caenorhabditis elegans Ciliogenesis

2008 ◽  
Vol 19 (5) ◽  
pp. 2154-2168 ◽  
Author(s):  
Corey L. Williams ◽  
Marlene E. Winkelbauer ◽  
Jenny C. Schafer ◽  
Edward J. Michaud ◽  
Bradley K. Yoder
Keyword(s):  
Caenorhabditis Elegans ◽  
Joubert Syndrome ◽  
Cystic Kidney ◽  
Basal Bodies ◽  
The Novel ◽  
C Elegans ◽  
Human Genes ◽  
Cilia Formation ◽  
Strong Candidate ◽  
Candidate Loci

Meckel-Gruber syndrome (MKS), nephronophthisis (NPHP), and Joubert syndrome (JBTS) are a group of heterogeneous cystic kidney disorders with partially overlapping loci. Many of the proteins associated with these diseases interact and localize to cilia and/or basal bodies. One of these proteins is MKS1, which is disrupted in some MKS patients and contains a B9 motif of unknown function that is found in two other mammalian proteins, B9D2 and B9D1. Caenorhabditis elegans also has three B9 proteins: XBX-7 (MKS1), TZA-1 (B9D2), and TZA-2 (B9D1). Herein, we report that the C. elegans B9 proteins form a complex that localizes to the base of cilia. Mutations in the B9 genes do not overtly affect cilia formation unless they are in combination with a mutation in nph-1 or nph-4, the homologues of human genes (NPHP1 and NPHP4, respectively) that are mutated in some NPHP patients. Our data indicate that the B9 proteins function redundantly with the nephrocystins to regulate the formation and/or maintenance of cilia and dendrites in the amphid and phasmid ciliated sensory neurons. Together, these data suggest that the human homologues of the novel B9 genes B9D2 and B9D1 will be strong candidate loci for pathologies in human MKS, NPHP, and JBTS.

Effect of structurally related flavonoids from Zuccagnia punctata Cav. on Caenorhabditis elegans

2014 ◽  
Vol 60 (1) ◽  
Author(s):  
Romina E. D’Almeida ◽  
María R. Alberto ◽  
Phillip Morgan ◽  
Margaret Sedensky ◽  
María I. Isla
Keyword(s):  
Caenorhabditis Elegans ◽  
Larval Development ◽  
Free Living ◽  
Egg Hatching ◽  
C Elegans ◽  
Therapeutic Drugs ◽  
Aerial Parts ◽  
Free Living Nematode ◽  
Development Processes ◽  
Anthelmintic Effect

AbstractZuccagnia punctata Cav. (Fabaceae), commonly called jarilla macho or pus-pus, is being used in traditional medicine as an antiseptic, anti-inflammatory and to relieve muscle and bone pain. The aim of this work was to study the anthelmintic effects of three structurally related flavonoids present in aerial parts of Z. punctata Cav. The biological activity of the flavonoids 7-hydroxyflavanone (HF), 3,7-dihydroxyflavone (DHF) and 2´,4´-dihydroxychalcone (DHC) was examined in the free-living nematode Caenorhabditis elegans. Our results showed that among the assayed flavonoids, only DHC showed an anthelmintic effect and alteration of egg hatching and larval development processes in C. elegans. DHC was able to kill 50% of adult nematodes at a concentration of 17 μg/mL. The effect on larval development was observed after 48 h in the presence of 25 and 50 μg/mL DHC, where 33.4 and 73.4% of nematodes remained in the L3 stage or younger. New therapeutic drugs with good efficacy against drug-resistant nematodes are urgently needed. Therefore, DHC, a natural compound present in Z. punctata, is proposed as a potential anthelmintic drug.

MUTATIONS WITH DOMINANT EFFECTS ON THE BEHAVIOR AND MORPHOLOGY OF THE NEMATODE CAENORHABDITIS ELEGANS

Genetics ◽  
1986 ◽  
Vol 113 (4) ◽  
pp. 821-852
Author(s):  
Eun-Chung Park ◽  
H Robert Horvitz
Keyword(s):  
Caenorhabditis Elegans ◽  
Random Sample ◽  
Gene Function ◽  
The Novel ◽  
Wild Type ◽  
Nematode Caenorhabditis Elegans ◽  
Type Function ◽  
C Elegans ◽  
Wild Type Phenotype ◽  
Gene Functions

ABSTRACT We have analyzed 31 mutations that have dominant effects on the behavior or morphology of the nematode Caenorhabditis elegans. These mutations appear to define 15 genes. We have studied ten of these genes in some detail and have been led to two notable conclusions. First, loss of gene function for four of these ten genes results in a wild-type phenotype; if these genes represent a random sample from the genome, then we would estimate that null mutations in about half of the genes in C. elegans would result in a nonmutant phenotype. Second, the dominant effects of mutations in nine of these ten genes are caused by novel gene functions, and in all nine cases the novel function is antagonized by the wild-type function.

scholarly journals pathDIP 4: an extended pathway annotations and enrichment analysis resource for human, model organisms and domesticated species

2019 ◽  
Author(s):  
Sara Rahmati ◽  
Mark Abovsky ◽  
Chiara Pastrello ◽  
Max Kotlyar ◽  
Richard Lu ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Enrichment Analysis ◽  
Human Model ◽  
Model Organisms ◽  
Pathway Enrichment Analysis ◽  
Protein Protein Interactions ◽  
Proteome Coverage ◽  
Pathway Annotation ◽  
Human Proteins ◽  
Integrated Pathway

Abstract PathDIP was introduced to increase proteome coverage of literature-curated human pathway databases. PathDIP 4 now integrates 24 major databases. To further reduce the number of proteins with no curated pathway annotation, pathDIP integrates pathways with physical protein–protein interactions (PPIs) to predict significant physical associations between proteins and curated pathways. For human, it provides pathway annotations for 5366 pathway orphans. Integrated pathway annotation now includes six model organisms and ten domesticated animals. A total of 6401 core and ortholog pathways have been curated from the literature or by annotating orthologs of human proteins in the literature-curated pathways. Extended pathways are the result of combining these pathways with protein-pathway associations that are predicted using organism-specific PPIs. Extended pathways expand proteome coverage from 81 088 to 120 621 proteins, making pathDIP 4 the largest publicly available pathway database for these organisms and providing a necessary platform for comprehensive pathway-enrichment analysis. PathDIP 4 users can customize their search and analysis by selecting organism, identifier and subset of pathways. Enrichment results and detailed annotations for input list can be obtained in different formats and views. To support automated bioinformatics workflows, Java, R and Python APIs are available for batch pathway annotation and enrichment analysis. PathDIP 4 is publicly available at http://ophid.utoronto.ca/pathDIP.

Identification of Potential Core Genes and Potential Drugs in Vestibular Schwannoma

2021 ◽  
Author(s):  
Junqiang Yan ◽  
Anran Liu ◽  
Jiarui Huang ◽  
Jiannan Wu ◽  
Hongxia Ma ◽  
...  
Keyword(s):  
Vestibular Schwannoma ◽  
Protein Interactions ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Pathway Enrichment Analysis ◽  
Data Sets ◽  
Protein Protein Interactions ◽  
Potential Core ◽  
Normal Tissues ◽  
Therapeutic Drugs

Abstract Vestibular schwannoma is a common intracranial benign tumor, but the current drug treatment effect is not obvious. Surgical treatment can usually lead to residual problems such as nerve damage. Therefore, there is no clear molecular target to facilitate better clinical treatment. We analyzed three microarray data sets (GSE39645, GSE54934 and GSE108524) derived from the Gene Expression Omnibus database (GEO). The GEO2R was used to screen for the differentially expressed genes (DEG) between vestibular schwannomas and normal tissues. The ontology function of genes and genome pathway enrichment analysis were performed using annotation, visualizative and comprehensive discovery databases to identify the pathways and functional annotation of DEGs. The protein-protein interactions of these DEGs were analyzed by searching the interaction gene database and visualized by Cytoscape software. The potential therapeutic drugs for vestibular schwannoma were searched by online gene drug interaction analysis.A total of 226 up-regulated and 148 down-regulated DEGs were identified. Among them, ten hub genes with high connectivity (EGFR, PPARG, CD86, CSF1R, SPP1, CDH2, CCND1, CAV1, CYBB and NCAM1) were selected as the central genes that may be closely related to the pathogenesis of vestibular schwannoma, which can be potential treatment targets of vestibular schwannoma. Afatinib and osimerinib may be potential therapeutic drugs.

scholarly journals Volatile Anesthetic Preconditioning Present in the Invertebrate Caenorhabditis elegans 

2008 ◽  
Vol 108 (3) ◽  
pp. 426-433 ◽  
Author(s):  
Baosen Jia ◽  
C Michael Crowder
Keyword(s):  
Caenorhabditis Elegans ◽  
Cellular Response ◽  
Volatile Anesthetic ◽  
The Novel ◽  
Loss Of Function ◽  
Nematode Caenorhabditis Elegans ◽  
C Elegans ◽  
Anesthetic Preconditioning ◽  
Evolutionarily Conserved ◽  
Duration Of Protection

Background Volatile anesthetics (VAs) have been found to induce a delayed protective response called preconditioning to subsequent hypoxic/ischemic injury. VA preconditioning has been primarily studied in canine and rodent heart. A more genetically tractable model of VA preconditioning would be extremely useful. Here, the authors report the development of the nematode Caenorhabditis elegans as a model of VA preconditioning. Methods Wild-type and mutant C. elegans were exposed to isoflurane, halothane, or air under otherwise identical conditions. After varying recovery periods, the animals were challenged with hypoxic, azide, or hyperthermic incubations. After recovery from these incubations, mortality was scored. Results Isoflurane- and halothane-preconditioned animals had significantly reduced mortality to all three types of injuries compared with air controls. Concentrations as low as 1 vol% isoflurane (0.64 mm) and halothane (0.71 mm) induced significant protection. The onset and duration of protection after anesthetic were 6 and 9 h, respectively. A mutation that blocks inhibition of neurotransmitter release by isoflurane did not attenuate the preconditioning effect. A loss-of-function mutation of the Apaf-1 homolog CED-4 blocked the preconditioning effect of isoflurane, but mutation of the downstream caspase CED-3 did not. Conclusions Volatile anesthetic preconditioning extends beyond the vertebrate subphylum. This markedly broadens the scope of VA preconditioning and suggests that its mechanisms are widespread across species and is a fundamental and evolutionarily conserved cellular response. C. elegans offers a means to dissect genetically the mechanism for VA preconditioning as illustrated by the novel finding of the requirement for the Apaf-1 homolog CED-4.

scholarly journals Characterization of aminopeptidase encoding gene anp-1 and its association with development in Caenorhabditis elegans

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7944 ◽  
Author(s):  
Shanchun Su ◽  
Baoliang Pan ◽  
Yanxin Hu ◽  
Ming Wang
Keyword(s):  
Caenorhabditis Elegans ◽  
Transcriptome Sequencing ◽  
Adult Stage ◽  
Small Body ◽  
Enrichment Analysis ◽  
Functional Expression ◽  
C Elegans ◽  
Sequencing Method ◽  
Differential Expression Genes ◽  
Development And Aging

Background Aminopeptidases play important roles in various biological processes in nematodes including growth, development and reproduction. Although the aminopeptidases have been shown to regulate reproduction in Caenorhabditis elegans (C. elegans), the role of aminopeptidases in development and aging has not been reported. This study focused on the function of aminopeptidase AlaNyl aminopeptidase 1 (ANP-1) on development in C. elegans. Methods In the present study, we reported the identification of ANP-1 in C. elegans along with sequence analysis and its functional expression and characterization. The phenotype changes were observed when anp-1 mutated. Then, differential expression genes (DEGs) between wild type strain (N2) and anp-1 deletion strain (RB804) were identified using transcriptome sequencing method. Finally, DEGs were verified by qRT-PCR assay. Results Our observations suggested that anp-1 mutation induced small body size in the L4/young adult stage of C. elegans, however, there was no difference between N2 and RB804 in adult stage. Moreover, deletion of anp-1 resulted in shortening lifespan and laying fewer eggs. DEGs (184 genes) were observed between N2 groups and RB804 groups by transcriptome sequencing. According to GO annotations and KEGG enrichment analysis, these DEGs play vital roles in development regulation in C. elegans. These data demonstrate ANP-1 participates in development and aging of C. elegans and will considerably contribute to the existing knowledge of aminopeptidase function in C. elegans.

scholarly journals Pathway-specific model estimation for improved pathway annotation by network crosstalk

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Miguel Castresana-Aguirre ◽  
Erik L. L. Sonnhammer
Keyword(s):  
Enrichment Analysis ◽  
High Sensitivity ◽  
Specific Model ◽  
Pathway Enrichment Analysis ◽  
Biological Processes ◽  
Biologically Relevant ◽  
Pathway Enrichment ◽  
Pathway Annotation ◽  
Gene Sets ◽  
Altered Gene

Abstract Pathway enrichment analysis is the most common approach for understanding which biological processes are affected by altered gene activities under specific conditions. However, it has been challenging to find a method that efficiently avoids false positives while keeping a high sensitivity. We here present a new network-based method ANUBIX based on sampling random gene sets against intact pathway. Benchmarking shows that ANUBIX is considerably more accurate than previous network crosstalk based methods, which have the drawback of modelling pathways as random gene sets. We demonstrate that ANUBIX does not have a bias for finding certain pathways, which previous methods do, and show that ANUBIX finds biologically relevant pathways that are missed by other methods.

scholarly journals Resiniferatoxin hampers the nocifensive response of Caenorhabditis elegans to noxious heat, and pathway analysis revealed that the Wnt signaling pathway is involved

2021 ◽  
Author(s):  
Jennifer Ben Salem ◽  
Bruno Nkambeu ◽  
Dina Arvanitis ◽  
Francis Beaudry
Keyword(s):  
Caenorhabditis Elegans ◽  
Wnt Signaling ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Pathway Enrichment Analysis ◽  
Vanilloid Receptors ◽  
Noxious Heat ◽  
C Elegans ◽  
Transient Receptor

Resiniferatoxin (RTX) is a metabolite extracted from Euphorbia resinifera. RTX is a potent capsaicin analog with specific biological activities resulting from its agonist activity with the transient receptor potential channel vanilloid subfamily member 1 (TRPV1). RTX has been examined as a pain reliever, and more recently, investigated for its ability to desensitize cardiac sensory fibers expressing TRPV1 to improve chronic heart failure (CHF) outcomes using validated animal models. Caenorhabditis elegans (C. elegans) expresses orthologs of vanilloid receptors activated by capsaicin, producing antinociceptive effects. Thus, we used C. elegans to characterize the antinociceptive properties and performed proteomic profiling to uncover specific signaling networks. After exposure to RTX, wild-type (N2) and mutant C. elegans were placed on petri dishes divided into quadrants for heat stimulation. The thermal avoidance index was used to phenotype each tested C. elegans experimental group. The data revealed for the first time that RTX can hamper the nocifensive response of C. elegans to noxious heat. The effect was reversed 6 h after RTX exposure. Additionally, we identified the RTX target, the C. elegans transient receptor potential channel OCR-3. The proteomics and pathway enrichment analysis results suggest that Wnt signaling is triggered by the agonistic effects of RTX on C. elegans vanilloid receptors.

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