Fast deep neural correspondence for tracking and identifying neurons in C. elegans using semi-synthetic training

We present an automated method to track and identify neurons in C. elegans, called “fast Deep Learning Correspondence” or fDLC, based on the transformer network architecture. The model is trained once on empirically derived synthetic data and then predicts neural correspondence across held-out real animals via transfer learning. The same pre-trained model both tracks neurons across time and identifies corresponding neurons across individuals. Performance is evaluated against hand-annotated datasets, including NeuroPAL [1]. Using only position information, the method achieves 80.0% accuracy at tracking neurons within an individual and 65.8% accuracy at identifying neurons across individuals. Accuracy is even higher on a published dataset [2]. Accuracy reaches 76.5% when using color information from NeuroPAL. Unlike previous methods, fDLC does not require straightening or transforming the animal into a canonical coordinate system. The method is fast and predicts correspondence in 10 ms making it suitable for future real-time applications.

[1]  Mackenzie W. Mathis,et al.  Deep learning tools for the measurement of animal behavior in neuroscience , 2019, Current Opinion in Neurobiology.

[2]  Alan L. Yuille,et al.  Non-Rigid Point Set Registration by Preserving Global and Local Structures , 2016, IEEE Transactions on Image Processing.

[3]  Yuko Murakami,et al.  An annotation dataset facilitates automatic annotation of whole-brain activity imaging of C. elegans , 2019 .

[4]  Alexander M. Bronstein,et al.  Rock, Paper, and Scissors: extrinsic vs. intrinsic similarity of non-rigid shapes , 2007, 2007 IEEE 11th International Conference on Computer Vision.

[5]  Aravinthan D. T. Samuel,et al.  NeuroPAL: A Multicolor Atlas for Whole-Brain Neuronal Identification in C. elegans , 2020, Cell.

[6]  Zengcai V. Guo,et al.  Controlling interneuron activity in Caenorhabditis elegans to evoke chemotactic behavior , 2012, Nature.

[7]  Decoding locomotion from population neural activity in moving C. elegans , 2021, eLife.

[8]  Luca Antiga,et al.  Automatic differentiation in PyTorch , 2017 .

[9]  R. Prevedel,et al.  Brain-wide 3D imaging of neuronal activity in Caenorhabditis elegans with sculpted light , 2013, Nature Methods.

[10]  Eduardo Blancas Reyes,et al.  YASS: Yet Another Spike Sorter applied to large-scale multi-electrode array recordings in primate retina , 2020, bioRxiv.

[11]  Liam Paninski,et al.  Scalable approximate Bayesian inference for particle tracking data , 2018, ICML.

[12]  Mason Klein,et al.  Pan-neuronal imaging in roaming Caenorhabditis elegans , 2015, Proceedings of the National Academy of Sciences.

[13]  E. Myers,et al.  A 3D Digital Atlas of C. elegans and Its Application To Single-Cell Analyses , 2009, Nature Methods.

[14]  Joshua W. Shaevitz,et al.  SLEAP: Multi-animal pose tracking , 2020, bioRxiv.

[15]  Andriy Myronenko,et al.  Point Set Registration: Coherent Point Drift , 2009, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[16]  H. Kuhn The Hungarian method for the assignment problem , 1955 .

[17]  R. Yuste,et al.  EMC 2 : A versatile algorithm for robust tracking of calcium dynamics from individual neurons in behaving animals , 2021 .

[18]  Ashley N. Linder,et al.  Decoding locomotion from population neural activity in moving C. elegans , 2018, eLife.

[19]  Christopher M. Bishop,et al.  Pattern Recognition and Machine Learning, 2006 , 2012 .

[20]  Geoffrey E. Hinton,et al.  Layer Normalization , 2016, ArXiv.

[21]  Joshua W Shaevitz,et al.  Whole-brain calcium imaging with cellular resolution in freely behaving Caenorhabditis elegans , 2015, Proceedings of the National Academy of Sciences.

[22]  Harold W. Kuhn,et al.  The Hungarian method for the assignment problem , 1955, 50 Years of Integer Programming.

[23]  Erdem Varol,et al.  Neuron matching in C. elegans with robust approximate linear regression without correspondence , 2021, 2021 IEEE Winter Conference on Applications of Computer Vision (WACV).

[24]  Daniel R. Berger,et al.  Connectomes across development reveal principles of brain maturation in C. elegans , 2020, bioRxiv.

[25]  Aaron C. Koralek,et al.  Volitional modulation of optically recorded calcium signals during neuroprosthetic learning , 2014, Nature Neuroscience.

[26]  S. Brenner,et al.  The structure of the nervous system of the nematode Caenorhabditis elegans. , 1986, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[27]  Lukasz Kaiser,et al.  Attention is All you Need , 2017, NIPS.

[28]  Liam Paninski,et al.  Statistical Atlas of C. elegans Neurons , 2020, MICCAI.

[29]  Matthew D. DiFranco,et al.  A probabilistic atlas for cell identification. , 2019 .

[30]  Takayuki Teramoto,et al.  Deep-learning-based flexible pipeline for segmenting and tracking cells in 3D image time series for whole brain imaging , 2018, bioRxiv.

[31]  Sol Ah Lee,et al.  Graphical-model framework for automated annotation of cell identities in dense cellular images , 2020, bioRxiv.

[32]  J. Sulston Post-embryonic development in the ventral cord of Caenorhabditis elegans. , 1976, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[33]  Samouil L. Farhi,et al.  All-optical electrophysiology in mammalian neurons using engineered microbial rhodopsins , 2014, Nature Methods.

[34]  Peilun Dai,et al.  Feasibility of 3D Reconstruction of Neural Morphology Using Expansion Microscopy and Barcode-Guided Agglomeration , 2017, Front. Comput. Neurosci..

[35]  Joshua W. Shaevitz,et al.  Automatically tracking neurons in a moving and deforming brain , 2016, PLoS Comput. Biol..

[36]  Baba C. Vemuri,et al.  Robust Point Set Registration Using Gaussian Mixture Models , 2011, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[37]  Aravinthan D. T. Samuel,et al.  Optogenetic manipulation of neural activity in freely moving Caenorhabditis elegans , 2011, Nature Methods.

[38]  Graphical-model framework for automated annotation of cell identities in dense cellular images , 2021, eLife.

[39]  O. Hobert,et al.  The CeNGEN Project: The Complete Gene Expression Map of an Entire Nervous System , 2018, Neuron.

[40]  Liam Paninski,et al.  Neural Networks for Efficient Bayesian Decoding of Natural Images from Retinal Neurons , 2017, bioRxiv.

[41]  Xiao Liu,et al.  Straightening Caenorhabditis elegans images , 2007, Bioinform..

[42]  Rafael Yuste,et al.  Robust single neuron tracking of calcium imaging in behaving Hydra , 2020, bioRxiv.

[43]  Radford M. Neal Pattern Recognition and Machine Learning , 2007, Technometrics.

[44]  Liam Paninski,et al.  Extracting neural signals from semi-immobilized animals with deformable non-negative matrix factorization , 2020, bioRxiv.

[45]  Matthew M. Crane,et al.  Real-time multimodal optical control of neurons and muscles in freely-behaving Caenorhabditis elegans , 2011, Nature Methods.

[46]  Christopher M. Clark,et al.  Simultaneous optogenetic manipulation and calcium imaging in freely moving C. elegans , 2013, bioRxiv.

[47]  Rafael Yuste,et al.  Tracking Activity In a Deformable Nervous System With Motion Correction and Point-Set Registration , 2018, bioRxiv.