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Abstract Background Determining cell identity in volumetric images of tagged neuronal nuclei is an ongoing challenge in contemporary neuroscience. Frequently, cell identity is determined by aligning and matching tags to an “atlas” of labeled neuronal positions and other identifying characteristics. Previous analyses of such C. elegans  datasets have been hampered by the limited accuracy of such atlases, especially for neurons present in the ventral nerve cord, and also by time-consuming manual elements of the alignment process. Results We present a novel automated alignment method for sparse and incomplete point clouds of the sort resulting from typical C. elegans  fluorescence microscopy datasets. This method involves a tunable learning parameter and a kernel that enforces biologically realistic deformation. We also present a pipeline for creating alignment atlases from datasets of the recently developed NeuroPAL transgene. In combination, these advances allow us to label neurons in volumetric images with confidence much higher than previous methods. Conclusions We release, to the best of our knowledge, the most complete full-body C. elegans  3D positional neuron atlas, incorporating positional variability derived from at least 7 animals per neuron, for the purposes of cell-type identity prediction for myriad applications (e.g., imaging neuronal activity, gene expression, and cell-fate). 

We propose methods for estimating correspondence between two point sets under the presence of outliers in both the source and target sets. The proposed algorithms expand upon the theory of the regression without correspondence problem to estimate transformation coefficients using unordered multisets of covariates and responses. Previous theoretical analysis of the problem has been done in a setting where the responses are a complete permutation of the regressed covariates. This paper expands the problem setting by analyzing the cases where only a subset of the responses is a permutation of the regressed covariates in addition to some covariates possibly being adversarial outliers. We term this problem robust regression without correspondence and provide several algorithms based on random sample consensus for exact and approximate recovery in a noiseless and noisy one-dimensional setting as well as an approximation algorithm for multiple dimensions. The theoretical guarantees of the algorithms are verified in simulated data. We demonstrate an important computational neuroscience application of the proposed framework by demonstrating its effectiveness in a Caenorhabditis elegans neuron matching problem where the presence of outliers in both the source and target nematodes is a natural tendency 

Sex differences in the brain are prevalent throughout the animal kingdom and particularly well appreciated in the nematode C. elegans, where male animals contain a little studied set of 93 male-specific neurons. To make these neurons amenable for future study, we describe here how a multicolor reporter transgene, NeuroPAL, is capable of visualizing the distinct identities of all male specific neurons. We used NeuroPAL to visualize and characterize a number of features of the male-specific nervous system. We provide several proofs of concept for using NeuroPAL to identify the sites of expression of gfp-tagged reporter genes and for cellular fate analysis by analyzing the effect of removal of several developmental patterning genes on neuronal identity acquisition. We use NeuroPAL and its intrinsic cohort of more than 40 distinct differentiation markers to show that, even though male-specific neurons are generated throughout all four larval stages, they execute their terminal differentiation program in a coordinated manner in the fourth larval stage. This coordinated wave of differentiation, which we call “just-in-time" differentiation, couples neuronal maturation programs with the appearance of sexual organs.