A Complex Regulatory Network Coordinating Cell Cycles During<i>C. elegans</i>Development Is Revealed by a Genome-Wide RNAi Screen

Roy, Sarah H.; Tobin, David V.; Memar, Nadin; Beltz, Eleanor; Holmen, Jenna; Clayton, Joseph E.; Chiu, Daniel J; Young, Laura D; Green, Travis H; Lubin, Isabella; Liu, Yuying; Conradt, Barbara; Saito, R. Mako

doi:10.1534/g3.114.010546

Cited by 13 publications

(10 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, Clone Mapper identified 23 new targets with of score >1, 9 of which had a score >50 ( Supporting Information , Table S1 ). Similar results were obtained for the two other studies ( Fievet et al 2013 ; Roy et al 2014 ) ( Table 1 , Table S2 , and Table S3 ). In all cases, the novel targets identified with Clone Mapper formed part of a closely linked network ( Figure 6 ).…”

Section: Resultssupporting

confidence: 89%

“…A list of novel targets identified with Clone Mapper for the RNAi clones used by Fievet et al was used as input to GeneMania (yellow circles), together with the genes corresponding to the 14 mutant strains used in the study (black circles). (C) Roy et al performed a screen to find components of a regulatory network that promotes developmentally programmed cell-cycle quiescence ( Roy et al 2014 ). Novel targets identified with Clone Mapper for the RNAi clones used by Roy et al (yellow), together with common targets (black) were used as input to GeneMania.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Clone Mapper: An Online Suite of Tools for RNAi Experiments in Caenorhabditis elegans

Thakur

Pujol

Tichit

et al. 2014

G3 Genes|Genomes|Genetics

View full text Add to dashboard Cite

RNA interference (RNAi), mediated by the introduction of a specific double-stranded RNA, is a powerful method to investigate gene function. It is widely used in the Caenorhabditis elegans research community. An expanding number of laboratories conduct genome-wide RNAi screens, using standard libraries of bacterial clones each designed to produce a specific double-stranded RNA. Proper interpretation of results from RNAi experiments requires a series of analytical steps, from the verification of the identity of bacterial clones, to the identification of the clones’ potential targets. Despite the popularity of the technique, no user-friendly set of tools allowing these steps to be carried out accurately, automatically, and at a large scale, is currently available. We report here the design and production of Clone Mapper, an online suite of tools specifically adapted to the analysis pipeline typical for RNAi experiments with C. elegans. We show that Clone Mapper overcomes the limitations of existing techniques and provide examples illustrating its potential for the identification of biologically relevant genes. The Clone Mapper tools are freely available via http://www.ciml.univ-mrs.fr/EWBANK_jonathan/software.html.

show abstract

Section: Resultssupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Clone Mapper: An Online Suite of Tools for RNAi Experiments in Caenorhabditis elegans

Thakur

Pujol

Tichit

et al. 2014

G3 Genes|Genomes|Genetics

View full text Add to dashboard Cite

show abstract

“…To characterize the physiological activity that promotes the rapid responses we observed, we monitored calcium levels in freely behaving animals using the genetically encoded indicator GCaMP3.0 [ 47 ]. Our behavioral assays indicated that egl-1 mutants, lacking the HSN serotonergic neuron type [ 48 , 49 ], were indistinguishable from wild-type (data not shown). Therefore, to study cellular mechanisms, we focused on the physiological activity in NSM and ADF prior to, during, and after re-feeding encounters.…”

Section: Resultsmentioning

confidence: 99%

Serotonin promotes exploitation in complex environments by accelerating decision-making

et al. 2016

View full text Add to dashboard Cite

BackgroundFast responses can provide a competitive advantage when resources are inhomogeneously distributed. The nematode Caenorhabditis elegans was shown to modulate locomotion on a lawn of bacterial food in serotonin (5-HT)-dependent manners. However, potential roles for serotonergic signaling in responding to food discovery are poorly understood.ResultsWe found that 5-HT signaling in C. elegans facilitates efficient exploitation in complex environments by mediating a rapid response upon encountering food. Genetic or cellular manipulations leading to deficient serotonergic signaling resulted in gradual responses and defective exploitation of a patchy foraging landscape. Physiological imaging revealed that the NSM serotonergic neurons responded acutely upon encounter with newly discovered food and were key to rapid responses. In contrast, the onset of responses of ADF serotonergic neurons preceded the physical encounter with the food. The serotonin-gated chloride channel MOD-1 and the ortholog of mammalian 5-HT1 metabotropic serotonin receptors SER-4 acted in synergy to accelerate decision-making. The relevance of responding rapidly was demonstrated in patchy environments, where the absence of 5-HT signaling was detrimental to exploitation.ConclusionsOur results implicate 5-HT in a novel form of decision-making, demonstrate its fitness consequences, suggest that NSM and ADF act in concert to modulate locomotion in complex environments, and identify the synergistic action of a channel and a metabotropic receptor in accelerating C. elegans decision-making.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-016-0232-y) contains supplementary material, which is available to authorized users.

show abstract

“…However, this form limited its utility and may have led to some confusion when searching for worm genes with human orthologs, as evidenced by publications that referenced OL1, but missed genes that were in the spreadsheet and thus reported a lower degree of reliability for this list (e.g. Roy et al 2014). To facilitate access, we subsequently developed a basic online tool, which was never formally published but instead publicized through a reader comment at the original journal Web site and announcements in C. elegans venues.…”

Section: The Legacy Gene Setmentioning

confidence: 99%

OrthoList 2: A New Comparative Genomic Analysis of Human and Caenorhabditis elegans Genes

et al. 2018

View full text Add to dashboard Cite

OrthoList, a compendium of Caenorhabditis elegans genes with human orthologs compiled in 2011 by a meta-analysis of four orthology-prediction methods, has been a popular tool for identifying conserved genes for research into biological and disease mechanisms. However, the efficacy of orthology prediction depends on the accuracy of gene-model predictions, an ongoing process, and orthology-prediction algorithms have also been updated over time. Here we present OrthoList 2 (OL2), a new comparative genomic analysis between C. elegans and humans, and the first assessment of how changes over time affect the landscape of predicted orthologs between two species. Although we find that updates to the orthology-prediction methods significantly changed the landscape of C. elegans-human orthologs predicted by individual programs and-unexpectedly-reduced agreement among them, we also show that our meta-analysis approach "buffered" against changes in gene content. We show that adding results from more programs did not lead to many additions to the list and discuss reasons to avoid assigning "scores" based on support by individual orthology-prediction programs; the treatment of "legacy" genes no longer predicted by these programs; and the practical difficulties of updating due to encountering deprecated, changed, or retired gene identifiers. In addition, we consider what other criteria may support claims of orthology and alternative approaches to find potential orthologs that elude identification by these programs. Finally, we created a new web-based tool that allows for rapid searches of OL2 by gene identifiers, protein domains [InterPro and SMART (Simple Modular Architecture Research Tool], or human disease associations ([OMIM (Online Mendelian Inheritence in Man], and also includes available RNA-interference resources to facilitate potential translational cross-species studies. KEYWORDS genome; homology; Caenorhabditis elegans; human S TUDIES in Caenorhabditis elegans have illuminated many mechanisms relevant to human biology and disease. Forward genetic screens based on phenotype have identified genes homologous to human disease-associated genes, illuminating fundamental properties about their roles and mechanisms of action (e.g., Greenwald 2012; Sundaram 2013; Golden 2017; van der Bliek et al. 2017). Reverse genetic methods have expanded the repertoire of possible genetic approaches. These methods include the ability to phenocopy loss-of-function mutations by feeding worms bacteria expressing double-stranded RNA (Fire et al. 1998; Timmons and Fire 1998). The efficiency of RNA interference (RNAi) in C. elegans has allowed for genome-wide screens (Fraser et al. 2000; Kamath et al. 2003; O'Reilly et al. 2016), or screens targeted to specific conserved genes, such as human disease genes (e.g., Sin et al. 2014; Vahdati Nia et al. 2017; Nordquist et al. 2018) or those involved in fundamental biological processes (e.g., Balklava et al. 2007; Dunn et al. 2010; Firnhaber and Hammarlund 2013; Allen et al. 2014; Du et al. 2015). Other...

show abstract

A Complex Regulatory Network Coordinating Cell Cycles DuringC. elegansDevelopment Is Revealed by a Genome-Wide RNAi Screen

Cited by 13 publications

References 83 publications

Clone Mapper: An Online Suite of Tools for RNAi Experiments in Caenorhabditis elegans

Clone Mapper: An Online Suite of Tools for RNAi Experiments in Caenorhabditis elegans

Serotonin promotes exploitation in complex environments by accelerating decision-making

OrthoList 2: A New Comparative Genomic Analysis of Human and Caenorhabditis elegans Genes

Contact Info

Product

Resources

About