scholarly journals Quantitative and Automated High-throughput Genome-wide RNAi Screens in C. elegans

10.3791/3448 ◽  
2012 ◽  
Author(s):  
Barbara Squiban ◽  
Jérôme Belougne ◽  
Jonathan Ewbank ◽  
Olivier Zugasti
Keyword(s):  
High Throughput ◽  
C Elegans ◽  
Genome Wide

High-Throughput, Liquid-Based Genome-Wide RNAi Screening in C. elegans

2016 ◽  
pp. 151-162 ◽  
Author(s):  
Linda P. O’Reilly ◽  
Ryan R. Knoerdel ◽  
Gary A. Silverman ◽  
Stephen C. Pak
Keyword(s):  
High Throughput ◽  
Rnai Screening ◽  
C Elegans ◽  
Genome Wide

scholarly journals High-throughput single-cell chromatin accessibility CRISPR screens enable unbiased identification of regulatory networks in cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sarah E. Pierce ◽  
Jeffrey M. Granja ◽  
William J. Greenleaf
Keyword(s):  
Transcription Factor ◽  
Single Cell ◽  
Cancer Cells ◽  
High Throughput ◽  
Regulatory Networks ◽  
Temporal Dynamics ◽  
Chromatin Accessibility ◽  
Regulatory Regions ◽  
Factor Binding ◽  
Genome Wide

AbstractChromatin accessibility profiling can identify putative regulatory regions genome wide; however, pooled single-cell methods for assessing the effects of regulatory perturbations on accessibility are limited. Here, we report a modified droplet-based single-cell ATAC-seq protocol for perturbing and evaluating dynamic single-cell epigenetic states. This method (Spear-ATAC) enables simultaneous read-out of chromatin accessibility profiles and integrated sgRNA spacer sequences from thousands of individual cells at once. Spear-ATAC profiling of 104,592 cells representing 414 sgRNA knock-down populations reveals the temporal dynamics of epigenetic responses to regulatory perturbations in cancer cells and the associations between transcription factor binding profiles.

scholarly journals A high-throughput genome-wide RNAi screen identifies modifiers of survival motor neuron protein

Cell Reports ◽  
2021 ◽  
Vol 35 (6) ◽  
pp. 109125
Author(s):  
Nikki M. McCormack ◽  
Mahlet B. Abera ◽  
Eveline S. Arnold ◽  
Rebecca M. Gibbs ◽  
Scott E. Martin ◽  
...  
Keyword(s):  
Motor Neuron ◽  
High Throughput ◽  
Rnai Screen ◽  
Survival Motor Neuron ◽  
Survival Motor Neuron Protein ◽  
Genome Wide ◽  
Motor Neuron Protein

scholarly journals Natural variation in fecundity is correlated with species-wide levels of divergence in Caenorhabditis elegans

2021 ◽  
Author(s):  
Gaotian Zhang ◽  
Jake D Mostad ◽  
Erik C Andersen
Keyword(s):  
Life History ◽  
Caenorhabditis Elegans ◽  
Life History Traits ◽  
Life History Trait ◽  
Selective Sweeps ◽  
C Elegans ◽  
Genome Wide ◽  
Genetic Complexity ◽  
Genomic Regions ◽  
Global Population

Abstract Life history traits underlie the fitness of organisms and are under strong natural selection. A new mutation that positively impacts a life history trait will likely increase in frequency and become fixed in a population (e.g. a selective sweep). The identification of the beneficial alleles that underlie selective sweeps provides insights into the mechanisms that occurred during the evolution of a species. In the global population of Caenorhabditis elegans, we previously identified selective sweeps that have drastically reduced chromosomal-scale genetic diversity in the species. Here, we measured the fecundity of 121 wild C. elegans strains, including many recently isolated divergent strains from the Hawaiian islands and found that strains with larger swept genomic regions have significantly higher fecundity than strains without evidence of the recent selective sweeps. We used genome-wide association (GWA) mapping to identify three quantitative trait loci (QTL) underlying the fecundity variation. Additionally, we mapped previous fecundity data from wild C. elegans strains and C. elegans recombinant inbred advanced intercross lines that were grown in various conditions and detected eight QTL using GWA and linkage mappings. These QTL show the genetic complexity of fecundity across this species. Moreover, the haplotype structure in each GWA QTL region revealed correlations with recent selective sweeps in the C. elegans population. North American and European strains had significantly higher fecundity than most strains from Hawaii, a hypothesized origin of the C. elegans species, suggesting that beneficial alleles that caused increased fecundity could underlie the selective sweeps during the worldwide expansion of C. elegans.

scholarly journals High-throughput behavioral screen in C. elegans reveals Parkinson’s disease drug candidates

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Salman Sohrabi ◽  
Danielle E. Mor ◽  
Rachel Kaletsky ◽  
William Keyes ◽  
Coleen T. Murphy
Keyword(s):  
Neural Network ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
High Throughput ◽  
Potential Candidate ◽  
Automated Scoring ◽  
C Elegans ◽  
Drug Candidates ◽  
Branched Chain ◽  
Approved Drugs

AbstractWe recently linked branched-chain amino acid transferase 1 (BCAT1) dysfunction with the movement disorder Parkinson’s disease (PD), and found that RNAi-mediated knockdown of neuronal bcat-1 in C. elegans causes abnormal spasm-like ‘curling’ behavior with age. Here we report the development of a machine learning-based workflow and its application to the discovery of potentially new therapeutics for PD. In addition to simplifying quantification and maintaining a low data overhead, our simple segment-train-quantify platform enables fully automated scoring of image stills upon training of a convolutional neural network. We have trained a highly reliable neural network for the detection and classification of worm postures in order to carry out high-throughput curling analysis without the need for user intervention or post-inspection. In a proof-of-concept screen of 50 FDA-approved drugs, enasidenib, ethosuximide, metformin, and nitisinone were identified as candidates for potential late-in-life intervention in PD. These findings point to the utility of our high-throughput platform for automated scoring of worm postures and in particular, the discovery of potential candidate treatments for PD.

scholarly journals Population genetic analysis and phylogeny reconstruction in Eucalyptus (Myrtaceae) using high-throughput, genome-wide genotyping

2011 ◽  
Vol 59 (1) ◽  
pp. 206-224 ◽  
Author(s):  
Dorothy A. Steane ◽  
Dean Nicolle ◽  
Carolina P. Sansaloni ◽  
César D. Petroli ◽  
Jason Carling ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
High Throughput ◽  
Population Genetic ◽  
Phylogeny Reconstruction ◽  
Population Genetic Analysis ◽  
Genome Wide

Genome-wide high throughput analysis of DNA methylation in eukaryotes

Methods ◽  
2009 ◽  
Vol 47 (3) ◽  
pp. 142-150 ◽  
Author(s):  
Kyle R. Pomraning ◽  
Kristina M. Smith ◽  
Michael Freitag
Keyword(s):  
Dna Methylation ◽  
High Throughput ◽  
High Throughput Analysis ◽  
Throughput Analysis ◽  
Genome Wide
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