An open source platform for analyzing and sharing worm behavior data

Javer, Avelino; Currie, Michael; Lee, Chee Wai; Hokanson, Jim; Li, Kezhi; Martineau, Céline N.; Yemini, Eviatar; Grundy, Laura J; Li, Chris; Ch'ng, Quee-Lim; Schafer, William R; Nollen, Ellen A. A.; Kerr, Rex; Brown, André Ex

doi:10.1101/377960

Cited by 30 publications

(46 citation statements)

References 29 publications

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“…All videos were analyzed using Tierpsy Tracker [73] to extract each worm's position and posture over time. These postural data were then converted into a set of behavioral features as previously described [53].…”

Section: Behavioral Feature Extraction and Analysismentioning

confidence: 99%

A terminal selector prevents a Hox transcriptional switch to safeguard motor neuron identity throughout life

Feng

Dao

et al. 2019

Preprint

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149/150 words)Nervous system function critically relies on continuous expression of neuron type-specific terminal identity features, such as neurotransmitter receptors, ion channels and neuropeptides. How individual neuron types select such features during development and maintain them throughout life is poorly understood. Here, we report an unconventional mechanism that enables cholinergic motor neurons (MNs) in the C. elegans ventral nerve cord to select and maintain their distinct terminal identity features. The conserved terminal selector UNC-3 (Collier/Ebf) UNC-3 is continuously required not only to promote cholinergic MN features, but also to prevent expression of "unwanted" terminal identity features normally reserved for other neuron types. Mechanistically, this dual function is achieved by the ability of UNC-3 to prevent a switch in the transcriptional targets of the Hox protein LIN-39 (Scr/Dfd/Hox4-5). The strategy of a terminal selector preventing a Hox transcriptional switch may constitute a general principle for safeguarding neuronal terminal identity features throughout life. 18]. Because they are present in both C. elegans sexes (males and hermaphrodites), we will refer to them as "sex-shared" MNs. In addition, there are two subtypes of "sex-specific" cholinergic MNs; the hermaphrodite-specific VC neurons control egg laying [19,20], whereas the male-specific CA neurons are required for mating [21] (Fig. 1A). Apart from distinct morphology and connectivity, each subtype can be molecularly defined based on the combinatorial expression of known terminal identity genes, such as ion channels, NT receptors, and neuropeptides ( Fig. 1B). An extensive collection of transgenic reporter animals for MN subtype-specific terminal identity genes is available, thereby providing a unique opportunity to investigate, at single-cell resolution, the effects of TF gene removal on 5 developing and adult MNs. UNC-3, the sole C. elegans ortholog of the Collier/Olf/Ebf (COE) family of TFs, is selectively expressed in all sex-shared cholinergic MNs of the nerve cord ( Fig. 1B) [22][23][24][25][26].Animals lacking unc-3 display striking locomotion defects [27]. UNC-3 is known to directly activate a large battery of terminal identity genes expressed either in all sex-shared cholinergic MNs (e.g., the NT identity genes unc-17/ VAChT and cha-1/ ChAT), or in certain subtypes (e.g., ion channels, NT receptors, signaling molecules) [23] ( Fig. 1B-C). Based on its ability to broadly co-regulate many distinct terminal identity features, unc-3 has been classified as a terminal selector gene [2]. Besides its well-established function as activator of terminal identity genes in cholinergic MNs, whether and how UNC-3 can prevent expression of "unwanted" terminal features remains unclear.Here, we identify a dual role for UNC-3 and describe an unconventional mechanism through which sex-shared cholinergic MNs select and maintain their terminal identity features. We find that UNC-3 is continuously required, from development through adulthood...

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Section: Behavioral Feature Extraction and Analysismentioning

confidence: 99%

A terminal selector prevents a Hox transcriptional switch to safeguard motor neuron identity throughout life

Feng

Dao

et al. 2019

Preprint

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“…In total we quantified 26 phenotypes for >18,000 animals across 87 genotypes and identified hundreds of novel genotype-phenotype relationships. Our database approximately doubles the number of animals in a recent aggregation of all other machine vision behavioral datasets collected in this organism to date, 138 and provides the first such systematic analysis that includes both complex sensory and learning phenotypes. By making the raw and processed data available online, we have created open and shareable phenotypic atlas of C. elegans strains carrying mutations in orthologs of ASD-associated genes.…”

Section: Discussionmentioning

confidence: 99%

Systematic phenomics analysis of ASD-associated genes reveals shared functions and parallel networks underlying reversible impairments in habituation learning

McDiarmid

Belmadani

Liang

et al. 2019

Preprint

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A major challenge facing the genetics of Autism Spectrum Disorders (ASD) is the large and growing number of candidate risk genes and gene variants of unknown functional significance.Here, we used Caenorhabditis elegans to systematically functionally characterize ASDassociated genes in vivo. Using our custom machine vision system we quantified 26 phenotypes spanning morphology, locomotion, tactile sensitivity, and habituation learning in 87 strains each carrying a mutation in an ortholog of an ASD-associated gene. We identified hundreds of novel genotype-phenotype relationships ranging from severe developmental delays and uncoordinated movement to subtle deficits in sensory and learning behaviors. We clustered genes by similarity in phenomic profiles and used epistasis analysis to discover parallel networks centered on CHD8•chd-7 and NLGN3•nlg-1 that underlie mechanosensory hyper-responsivity and impaired habituation learning. We then leveraged our data for in vivo functional assays to gauge missense variant effect. Expression of wild-type NLG-1 in nlg-1 mutant C. elegans rescued their sensory and learning impairments. Testing the rescuing ability of all conserved ASD-associated neuroligin variants revealed varied partial loss-of-function despite proper subcellular localization. Finally, we used CRISPR-Cas9 auxin inducible degradation to determine that phenotypic abnormalities caused by developmental loss of NLG-1 can be reversed by adult expression. This work charts the phenotypic landscape of ASDassociated genes, offers novel in vivo variant functional assays, and potential therapeutic targets for ASD.

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“…Videos were analysed with the freely available Worm Tracker 2.0 software to extract behavioural features as time series data 11 . The worm-behaviour data is available on an opensource platform 13 (http://movement.openworm.org/).…”

Section: Collection Of Behavioural Datamentioning

confidence: 99%

“…Importantly, the behaviour of C. elegans evolves from the first day of adulthood as a consequence of modified neuronal functions and progresses further as a consequence of the stochastic senescence of muscle cells (7). Hundreds of morphological and behavioural features extracted at once from high resolution videos of the worms was previously shown to produce meaningful classes of mutants [11][12][13] . We opted for this approach to build an unbiased multiple parameters database precisely describing the phenotypic progression of worms during ageing.…”

Section: Introductionmentioning

confidence: 99%

Deep behavioural phenotyping reveals divergent trajectories of ageing and quantifies health state inC. elegans

Baskaner

et al. 2019

Preprint

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Neurodegenerative diseases may be the cause or the consequence of an acceleration of physiological ageing. Evidence for this concept is lacking due to practical limitations of human studies. Here, we compared the processes of physiological and pathological ageing of individual C. elegans over their lifespan. Using multi-parametric phenotyping, trajectories of ageing can be defined within a phenotypic landscape made of a large set of phenotypical features. Rather than an acceleration of ageing, a model for synucleinopathy showed a divergent trajectory of ageing. The pathological progression in individual animals can be predicted from early phenotypes with high accuracy. Despite of similar lifespans, disease-model worms display an early onset of decline in their phenotypic range of ability. This loss of flexibility provides an index of health valid for physiological and pathological contexts. Finally, we demonstrate the power of multi-parametric dataset to describe ageing, to quantify health and to predict specific health risks.

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An open source platform for analyzing and sharing worm behavior data

Cited by 30 publications

References 29 publications

A terminal selector prevents a Hox transcriptional switch to safeguard motor neuron identity throughout life

A terminal selector prevents a Hox transcriptional switch to safeguard motor neuron identity throughout life

Systematic phenomics analysis of ASD-associated genes reveals shared functions and parallel networks underlying reversible impairments in habituation learning

Deep behavioural phenotyping reveals divergent trajectories of ageing and quantifies health state inC. elegans

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