Publications
63 results found
Brown AEX, de Bivort B, 2018, Ethology as a physical science, Publisher: bioRxiv
Behaviour is the ultimate output of an animal's nervous system and choosing the right action at the right time can be critical for survival. The study of the organisation of behaviour in its natural context, ethology, has historically been a primarily qualitative science. A quantitative theory of behaviour would advance research in neuroscience as well as ecology and evolution. However, animal posture typically has many degrees of freedom and behavioural dynamics vary on timescales ranging from milliseconds to years, presenting both technical and conceptual challenges. Here we review 1) advances in imaging and computer vision that are making it possible to capture increasingly complete records of animal motion and 2) new approaches to understanding the resulting behavioural data sets. With the right analytical approaches, these data are allowing researchers to revisit longstanding questions about the structure and organisation of animal behaviour and to put unifying principles on a quantitative footing. Contributions from both experimentalists and theorists are leading to the emergence of a physics of behaviour and the prospect of discovering laws and developing theories with broad applicability. We believe that there now exists an opportunity to develop theories of behaviour which can be tested using these data sets leading to a deeper understanding of how and why animals behave.
Li K, Javer A, Keaveny E, et al., 2018, Recurrent Neural Networks with Interpretable Cells Predict and Classify Worm Behaviour, Twenty-ninth Annual Conference on Neural Information Processing Systems (NIPS)
An important goal in behaviour analytics is to connect disease state or genomevariation with observable differences in behaviour. Despite advances in sensortechnology and imaging, informative behaviour quantification remains challenging.The nematode worm C. elegans provides a unique opportunity to test analysisapproaches because of its small size, compact nervous system, and the availabilityof large databases of videos of freely behaving animals with known genetic differences.Despite its relative simplicity, there are still no reports of generative modelsthat can capture essential differences between even well-described mutant strains.Here we show that a multilayer recurrent neural network (RNN) can produce diversebehaviours that are difficult to distinguish from real worms’ behaviour andthat some of the artificial neurons in the RNN are interpretable and correlate withobservable features such as body curvature, speed, and reversals. Although theRNN is not trained to perform classification, we find that artificial neuron responsesprovide features that perform well in worm strain classification.
Keaveny E, Brown AE, 2017, Predicting path from undulations for C. elegans using linear and nonlinear resistive force theory, Physical Biology, Vol: 14, ISSN: 1478-3975
A basic issuein the physics of behaviouris the mechanical relationship between an animal and its surroundings. The nematode and model organism C. elegans provides an excellent platform to explore this relationship due to its anatomical simplicity. Nonetheless,the physics of nematode crawling, in which the worm undulates its body to move on a wet surface, is not completely understoodand the mathematical models often used to describe this phenomenon are empirical. We confirm that linear resistive force theory, one such empirical model,is effective at predicting a worm’s path from its sequence of body postures for forward crawling, reversing, and turning and for a broad range of different behavioural phenotypes observedin mutant worms. However, agreement between the predicted and observed path is lost when using this model with recently measured valuesof the drag anisotropy. A recently proposed nonlinear extensionof the resistive force theory model also provides accurate predictions, but does not resolve the discrepancy between the parameters required to achieve good path prediction and the experimentally measured parameters. This meansthat while we have good effective models of worm crawling that can be used in applications such as whole-animal simulations and advanced tracking algorithms, there are still unanswered questions about the precise nature of the physical interaction between worms and their most commonly studied laboratory substrate.
Gomez-Marin A, Stephens GJ, Brown AE, 2016, Hierarchical compression of C. elegans locomotion reveals phenotypic differences in the organisation of behaviour, Journal of the Royal Society Interface, Vol: 13, ISSN: 1742-5689
Regularities in animal behaviour offer insight into the underlying organisational and functional principles of nervous systems and automated tracking provides the opportunity to extract featuresof behaviour directly from large-scale video data. Yet how to effectively analyse such behavioural data remains an open question. Here we explore whether a minimum description length principle can beexploited to identify meaningful behaviours and phenotypes. We apply a dictionary compression algorithm to behavioural sequences from the nematode worm Caenorhabditis elegans freely crawling on an agar plate both with and without food and during chemotaxis. We find that the motifs identified by the compression algorithm are rare but relevant for comparisons between worms in different environments, suggesting that hierarchical compression can be a useful step in behaviour analysis. We also use compressibility as a new quantitative phenotype and find that the behaviour of wild-isolated strains of C. elegans is more compressible than that of the laboratory strain N2 as well as the majority of mutant strains examined. Importantly, in distinction to more conventional phenotypes such as overall motor activity or aggregation behaviour, the increased compressibility of wild isolates is not explained by the loss of function of the gene npr-1, which suggests that erratic locomotion is a laboratory-derived trait with a novel genetic basis. Because hierarchical compression can be applied to any sequence, we anticipate that compressibility can offer insight into the organisation of behaviour in other animals including humans.
Brown AE, Gyenes B, 2016, Deriving shape-based features for C. elegans locomotion using dimensionality reduction methods, Frontiers in Behavioral Neuroscience, Vol: 10, ISSN: 1662-5153
High-throughput analysis of animal behavior is increasingly common following the advances of recording technology, leading to large high-dimensional data sets. This dimensionality can sometimes be reduced while still retaining relevant information. In the case of the nematode worm Caenorhabditis elegans, more than 90% of the shape variance can be captured using just four principal components. However, it remains unclear if other methods can achieve a more compact representation or contribute further biological insight to worm locomotion. Here we take a data-driven approach to worm shape analysis using independent component analysis (ICA), non-negative matrix factorization (NMF), a cosine series, and jPCA (a dynamic variant of principal component analysis [PCA]) and confirm that the dimensionality of worm shape space is close to four. Projecting worm shapes onto the bases derived using each method gives interpretable features ranging from head movements to tail oscillation. We use these as a comparison method to find differences between the wild type N2 worms and various mutants. For example, we find that the neuropeptide mutant nlp-1(ok1469) has an exaggerated head movement suggesting a mode of action for the previously described increased turning rate. The different bases provide complementary views of worm behavior and we expect that closer examination of the time series of projected amplitudes will lead to new results in the future.
Schwarz RF, Branicky R, Grundy LJ, et al., 2015, Changes in postural syntax characterize sensory modulation and natural variation of C. elegans locomotion, PLOS Computational Biology, Vol: 11, ISSN: 1553-734X
Locomotion is driven by shape changes coordinated by the nervous system through time;thus, enumerating an animal's complete repertoire of shape transitions would provide abasis for a comprehensive understanding of locomotor behaviour. Here we introduce a discreterepresentation of behaviour in the nematode C. elegans. At each point in time, theworm’s posture is approximated by its closest matching template from a set of 90 posturesand locomotion is represented as sequences of postures. The frequency distribution of posturalsequences is heavy-tailed with a core of frequent behaviours and a much larger set ofrarely used behaviours. Responses to optogenetic and environmental stimuli can be quantifiedas changes in postural syntax: worms show different preferences for differentsequences of postures drawn from the same set of templates. A discrete representation of behaviour will enable the use of methods developed for other kinds of discrete data in bioinformatics and language processing to be harnessed for the study of behaviour.
Koren Y, Sznitman R, Arratia PE, et al., 2015, Model-independent phenotyping of C. elegans locomotion using scale-invariant feature transform, PLOS One, Vol: 10, ISSN: 1932-6203
To uncover the genetic basis of behavioral traits in the model organism C. elegans, a common strategy is to study locomotion defects in mutants. Despite efforts to introduce (semi-)automated phenotyping strategies, current methods overwhelmingly depend on worm-specific features that must be hand-crafted and as such are not generalizable for phenotyping motility in other animal models. Hence, there is an ongoing need for robust algorithms that can automatically analyze and classify motility phenotypes quantitatively. To this end, we have developed a fully-automated approach to characterize C. elegans’ phenotypes that does not require the definition of nematode-specific features. Rather, we make use of the popular computer vision Scale-Invariant Feature Transform (SIFT) from which we construct histograms of commonly-observed SIFT features to represent nematode motility. We first evaluated our method on a synthetic dataset simulating a range of nematode crawling gaits. Next, we evaluated our algorithm on two distinct datasets of crawling C. elegans with mutants affecting neuromuscular structure and function. Not only is our algorithm able to detect differences between strains, results capture similarities in locomotory phenotypes that lead to clustering that is consistent with expectations based on genetic relationships. Our proposed approach generalizes directly and should be applicable to other animal models. Such applicability holds promise for computational ethology as more groups collect high-resolution image data of animal behavior.
Gulli S, Maddalena L, McKelvey C, et al., 2015, Characterization of complex porous structures for reusable thermal protection systems: Porosity measurements, Journal of Spacecraft and Rockets, Vol: 52, Pages: 166-176, ISSN: 0022-4650
This work is focused on the nonintrusive characterization of the local and average porosity of a prototype carbon-carbon nose, representative of a reusable thermal protection system based on transpiration cooling. A study based on the x-ray computed tomography scan of the specimen has been carried out with the purpose of defining the most important guidelines for the permeability tests, which are the minimum areatobeprobed with a hot-film anemometer and the correct distance of the mass flux sensor from the wall. The former has been calculated from the average porosity calculation, whereas the latter has been retrieved from the statistical analysis of the dimensions, and the distribution of the void structures inside the porous network coupled to the theory of fluid flow through perforated plates. Several longitudinal and transversal sectioning planes with respect to the symmetry axis of the carbon mask have been analyzed to calculate the internal porosity from the two-dimensional images, whereas the three-dimensional reconstruction of the sample has been used to retrieve the average volumetric porosity. Both the nominal values of the two-dimensional porosity and volumetric porosity have provided the same dimension of the characteristic area to be probed with a hot-film sensor for the permeability measurements. Preliminary permeability tests, performed within the predicted dimension of the control surface, have confirmed the uniformity of the mean velocity field and allowed verifying the range of variation of the correct distance of a hot-film sensor from the wall obtained from the statistical analysis of the computed tomography images.
Brown AEX, Schafer WR, 2015, Automated behavioural fingerprinting of caenorhabditis elegans mutants, Systems Genetics: Linking Genotypes and Phenotypes, Pages: 234-256, ISBN: 9781107013841
Rapid advances in genetics, genomics and imaging have given insight into the molecular and cellular basis of behaviour in a variety of model organisms with unprecedented detail and scope. It is increasingly becoming routine to isolate behavioural mutants, clone and characterise mutant genes and discern the molecular and neural basis for a behavioural phenotype. Conversely, reverse genetic approaches have made it possible to straightforwardly identify genes of interest in whole-genome sequences and generate mutants that can be subjected to phenotypic analysis. In this latter approach, it is the phenol typing that presents the major bottleneck; when it comes to connecting phenotype to genotype in freely behaving animals, analysis of behaviour itself remains superficial and time-consuming. However, many proof-of-principle studies of automated behavioural analysis over the last decade have poised the field on the verge of exciting developments that promise to begin closing this gap. In the broadest sense, our goal in this chapter is to explore what we can learn about the genes involved in neural function by carefully observing behaviour. This approach is rooted in model organism genetics but shares ideas with ethology and neuroscience, as well as computer vision and bioinformatics. After introducing Caenorhabditis elegans as a model, we will survey the research that has led to the current state of the art in worm behavioural phenol typing and present current research that is transforming our approach to behavioural genetics. The worm as a model organism Caenorhabditis elegans is a nematode worm that lives in bacteria-rich environments such as rotting fruit and has also been isolated from insects and snails which it is thought to use for longer-range transportation (Barriere and Felix 2005, Lee et al. 2011). In the laboratory, it is commonly cultured on the surface of agar plates seeded with a lawn of the bacterium Escherichia coli as a food source. On plates, worms lie
Yemini EI, Brown AEX, 2015, Tracking Single <i>C</i>. <i>elegans</i> Using a USB Microscope on a Motorized Stage, C. ELEGANS: METHODS AND APPLICATIONS, 2ND EDITION, Editors: Biron, Haspel, Publisher: HUMANA PRESS INC, Pages: 181-197, ISBN: 978-1-4939-2841-5
- Author Web Link
- Cite
- Citations: 1
Gulli S, Maddalena L, McKelvey C, et al., 2014, Permeability measurements of complex porous structures for reusable thermal protection systems (invited paper)
Reusable thermal protection systems are one of the key technologies that have to be improved in order to afford long-duration hypersonic flights. Transpiration cooling has been demonstrated to be one of the most promising active cooling techniques in terms of temperature decreasing and coolant mass saving. The coupling of the boundary layer with the thermal response of selected porous materials plays a crucial role in enabling the practical use of the transpiration cooling technique for reusable thermal protection systems. In this work, a novel test-rig for the non-intrusive characterization in terms of local permeability of a customized porous Carbon-Carbon nose-tip is proposed. The new concept of effective permeability, conceived as the local blowing capability of a porous structure with respect to a selected coolant fluid, is also introduced. The coolant (air) mass-fluxes blown from the porous surface of the specimen, and measured by a hot-film probe, are related to the average pressure gradient across the local material thickness by using the Darcy's law on prescribed locations. A parallel work, based on the X-Ray computed tomography scan of the prototype specimen, has been carried out with the purpose of defining the most important guidelines for the effective-permeability tests. Specifically, the calculation of the average porosity is used to define the minimum area to be probed with the hot-wire. The analysis of the statistical distribution of the void structures inside the C/C cone, coupled to the use of the theory of fluid-flow through perforated plates, is performed to determine the correct distance of the hot-wire from the wall. The results show permeability variation among the surveyed locations ranging from 6% to 172%. The effective-permeability map obtained allows classifying the prototype C/C mask as a semi-pervious structure. In particular, the higher effective permeability is located near the stagnation point region where two delaminations are locat
Yemini E, Jucikas T, Grundy LJ, et al., 2013, A database of <i>Caenorhabditis elegans</i> behavioral phenotypes, NATURE METHODS, Vol: 10, Pages: 877-+, ISSN: 1548-7091
- Author Web Link
- Cite
- Citations: 170
Brown AEX, Yemini EI, Grundy LJ, et al., 2013, A dictionary of behavioral motifs reveals clusters of genes affecting <i>Caenorhabditis elegans</i> locomotion, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 110, Pages: 791-796, ISSN: 0027-8424
- Author Web Link
- Cite
- Citations: 132
Russell CA, Fonville JM, Brown AEX, et al., 2012, The Potential for Respiratory Droplet-Transmissible A/H5N1 Influenza Virus to Evolve in a Mammalian Host, SCIENCE, Vol: 336, Pages: 1541-1547, ISSN: 0036-8075
- Author Web Link
- Cite
- Citations: 240
Rehfeldt F, Brown AEX, Raab M, et al., 2012, Hyaluronic acid matrices show matrix stiffness in 2D and 3D dictates cytoskeletal order and myosin-II phosphorylation within stem cells, INTEGRATIVE BIOLOGY, Vol: 4, Pages: 422-430, ISSN: 1757-9694
- Author Web Link
- Cite
- Citations: 94
Zhmurov A, Brown AEX, Litvinov RI, et al., 2011, Mechanism of Fibrin(ogen) Forced Unfolding, STRUCTURE, Vol: 19, Pages: 1615-1624, ISSN: 0969-2126
- Author Web Link
- Cite
- Citations: 91
Purohit PK, Litvinov RI, Brown AEX, et al., 2011, Protein unfolding accounts for the unusual mechanical behavior of fibrin networks, ACTA BIOMATERIALIA, Vol: 7, Pages: 2374-2383, ISSN: 1742-7061
- Author Web Link
- Cite
- Citations: 57
Brown AEX, Schafer WR, 2011, Unrestrained worms bridled by the light, NATURE METHODS, Vol: 8, Pages: 129-U43, ISSN: 1548-7091
- Author Web Link
- Cite
- Citations: 4
Rajagopal K, Mahmud A, Christian DA, et al., 2010, Curvature-Coupled Hydration of Semicrystalline Polymer Amphiphiles Yields flexible Worm Micelles but Favors Rigid Vesicles: Polycaprolactone-Based Block Copolymers, MACROMOLECULES, Vol: 43, Pages: 9736-9746, ISSN: 0024-9297
- Author Web Link
- Cite
- Citations: 104
Krieger CC, Bhasin N, Tewari M, et al., 2010, Exon-Skipped Dystrophins for Treatment of Duchenne Muscular Dystrophy: Mass Spectrometry Mapping of Most Exons and Cooperative Domain Designs Based on Single Molecule Mechanics, CYTOSKELETON, Vol: 67, Pages: 796-807, ISSN: 1949-3584
- Author Web Link
- Cite
- Citations: 17
Zemel A, Rehfeldt F, Brown AEX, et al., 2010, Optimal matrix rigidity for stress-fibre polarization in stem cells, NATURE PHYSICS, Vol: 6, Pages: 468-473, ISSN: 1745-2473
- Author Web Link
- Cite
- Citations: 299
Zemel A, Rehfeldt F, Brown AEX, et al., 2010, Cell shape, spreading symmetry, and the polarization of stress-fibers in cells, JOURNAL OF PHYSICS-CONDENSED MATTER, Vol: 22, ISSN: 0953-8984
- Author Web Link
- Cite
- Citations: 79
Buxboim A, Rajagopal K, Brown AEX, et al., 2010, How deeply cells feel: methods for thin gels, JOURNAL OF PHYSICS-CONDENSED MATTER, Vol: 22, ISSN: 0953-8984
- Author Web Link
- Cite
- Citations: 261
Brown AEX, Discher DE, 2009, Conformational Changes and Signaling in Cell and Matrix Physics, CURRENT BIOLOGY, Vol: 19, Pages: R781-R789, ISSN: 0960-9822
- Author Web Link
- Cite
- Citations: 63
Brown AEX, Litvinov RI, Discher DE, et al., 2009, Multiscale Mechanics of Fibrin Polymer: Gel Stretching with Protein Unfolding and Loss of Water, SCIENCE, Vol: 325, Pages: 741-744, ISSN: 0036-8075
- Author Web Link
- Cite
- Citations: 288
Brown AEX, Hategan A, Safer D, et al., 2009, Cross-Correlated TIRF/AFM Reveals Asymmetric Distribution of Force-Generating Heads along Self-Assembled, "Synthetic" Myosin Filaments, BIOPHYSICAL JOURNAL, Vol: 96, Pages: 1952-1960, ISSN: 0006-3495
- Author Web Link
- Cite
- Citations: 22
Vijayan K, Brown AE, Rajagopal K, et al., 2008, Glassy worms: From rheology to solvent tuned flexibility and nano-molded rods
Kulic IM, Brown AEX, Kim H, et al., 2008, The role of microtubule movement in bidirectional organelle transport, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 105, Pages: 10011-10016, ISSN: 0027-8424
- Author Web Link
- Cite
- Citations: 109
Brown AEX, Litvinov RI, Discher DE, et al., 2007, Forced unfolding of coiled-coils in fibrinogen by single-molecule AFM, BIOPHYSICAL JOURNAL, Vol: 92, Pages: L39-L41, ISSN: 0006-3495
- Author Web Link
- Cite
- Citations: 119
Bhasin N, Johnson C, Sen S, et al., 2005, Interface concentration dependence in unfolding proteins using AFM, Pages: 1307-1311
Filamin A is a long, high molecular mass (∼280 kDa) acting-binding protein, constituting of 24 Ig domains in a monomeric form. Filamin A cross-links F-actin into three-dimensional isotropic resilient, stiffer, more solid-like networks. Dysfunction or deletion of human filamin causes various genetic disorder or deformations in melanoma cells due to reduced stiffness of cortical actin. Filamin's key role in actin organization, membrane stabilization, and the anchoring of transmembrane cell receptor proteins to the actin cytoskeleton, suggests that filamin has an important mechanical function. Here we show by atomic force microscopy (AFM) that all repeats for filamin extend and unfold at similar forces as observed and analyzed through sawtooth patterns. This novel AFM based nano-biotechnology opens a molecular mechanic approach for studying structure to function related properties of any type of individual biological macromolecules. In order to study forced unfolding of sub-domains within filamin, the minimal possible forces to unfold native filamin must be determined by eliminating effects of multiple chains or loops as much as possible. Here we show that force for unfolding individual domains of intact filamin increase with the increase in protein concentration adsorbed on the substrate (mica/gold) and thus results into high range of forces for unfolding as reported in previous studies. Similar interfacial concentrations dependent AFM induced unfolding experiments were performed and verified on titin-(I27) 8 peptide. Further domain unfolding forces for full length filamin monomer were compared with its sub-domain constructs- (R15-R16) m - consisting of repeats 15 and 16.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.