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      Powerful and interpretable behavioural features for quantitative phenotyping of Caenorhabditis elegans

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          Abstract

          Behaviour is a sensitive and integrative readout of nervous system function and therefore an attractive measure for assessing the effects of mutation or drug treatment on animals. Video data provide a rich but high-dimensional representation of behaviour, and so the first step of analysis is often some form of tracking and feature extraction to reduce dimensionality while maintaining relevant information. Modern machine-learning methods are powerful but notoriously difficult to interpret, while handcrafted features are interpretable but do not always perform as well. Here, we report a new set of handcrafted features to compactly quantify Caenorhabditis elegans behaviour. The features are designed to be interpretable but to capture as much of the phenotypic differences between worms as possible. We show that the full feature set is more powerful than a previously defined feature set in classifying mutant strains. We then use a combination of automated and manual feature selection to define a core set of interpretable features that still provides sufficient power to detect behavioural differences between mutant strains and the wild-type. Finally, we apply the new features to detect time-resolved behavioural differences in a series of optogenetic experiments targeting different neural subsets.

          This article is part of a discussion meeting issue ‘Connectome to behaviour: modelling C. elegans at cellular resolution’.

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            High-Throughput Behavioral Analysis in C. elegans

            We have designed a real-time computer vision system, the Multi-Worm Tracker (MWT), that can simultaneously quantify the behavior of dozens of Caenorhabditis elegans on a traditional petri plate at video rates. Three traditional behavioral paradigms are examined using this system: spontaneous movement on food, where the behavior changes over tens of minutes; chemotaxis, where turning events must be detected accurately to determine strategy; and habituation of response to tap, where the response is stochastic and changes over time. In each case, manual analysis or automated single-worm tracking would be tedious and time-consuming, but the MWT system allows rapid quantification of behavior with minimal human effort. Thus, this system will enablelarge scale forward and reverse genetic screens for complex behaviors.
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              The fundamental role of pirouettes in Caenorhabditis elegans chemotaxis.

              To investigate the behavioral mechanism of chemotaxis in Caenorhabditis elegans, we recorded the instantaneous position, speed, and turning rate of single worms as a function of time during chemotaxis in gradients of the attractants ammonium chloride or biotin. Analysis of turning rate showed that each worm track could be divided into periods of smooth swimming (runs) and periods of frequent turning (pirouettes). The initiation of pirouettes was correlated with the rate of change of concentration (dC/dt) but not with absolute concentration. Pirouettes were most likely to occur when a worm was heading down the gradient (dC/dt 0). Further analysis revealed that the average direction of movement after a pirouette was up the gradient. These observations suggest that chemotaxis is produced by a series of pirouettes that reorient the animal to the gradient. We tested this idea by imposing the correlation between pirouettes and dC/dt on a stochastic point model of worm motion. The model exhibited chemotaxis behavior in a radial gradient and also in a novel planar gradient. Thus, the pirouette model of C. elegans chemotaxis is sufficient and general.
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                Author and article information

                Journal
                Philos Trans R Soc Lond B Biol Sci
                Philos. Trans. R. Soc. Lond., B, Biol. Sci
                RSTB
                royptb
                Philosophical Transactions of the Royal Society B: Biological Sciences
                The Royal Society
                0962-8436
                1471-2970
                19 October 2018
                10 September 2018
                10 September 2018
                : 373
                : 1758 , Discussion meeting issue ‘Connectome to behaviour: modelling C. elegans at cellular resolution’ organized and edited by Stephen D. Larson, Padraig Gleeson and André E.X. Brown
                : 20170375
                Affiliations
                [1 ]MRC London Institute of Medical Sciences , London, UK
                [2 ]Institute of Clinical Sciences, Imperial College London , London, UK
                Author notes

                One contribution of 15 to a discussion meeting issue ‘ Connectome to behaviour: modelling C. elegans at cellular resolution ’.

                Electronic supplementary material is available online at https://dx.doi.org/10.6084/m9.figshare.c.4195709.

                Author information
                http://orcid.org/0000-0002-1324-8764
                Article
                rstb20170375
                10.1098/rstb.2017.0375
                6158219
                30201839
                395b3683-3873-47dd-9444-e6d1efc42d38
                © 2018 The Authors.

                Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.

                History
                : 6 August 2018
                Funding
                Funded by: H2020 European Research Council, http://dx.doi.org/10.13039/100010663;
                Award ID: 714853
                Funded by: Medical Research Council, http://dx.doi.org/10.13039/501100000265;
                Award ID: MC-A658-5TY30
                Categories
                1001
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                Research Article
                Custom metadata
                October 19, 2018

                Philosophy of science
                computational ethology,c. elegans,phenotyping,worm tracking
                Philosophy of science
                computational ethology, c. elegans, phenotyping, worm tracking

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