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Blind demixing methods for recovering dense neuronal morphology from barcode imaging data.


ABSTRACT: Cellular barcoding methods offer the exciting possibility of 'infinite-pseudocolor' anatomical reconstruction-i.e., assigning each neuron its own random unique barcoded 'pseudocolor,' and then using these pseudocolors to trace the microanatomy of each neuron. Here we use simulations, based on densely-reconstructed electron microscopy microanatomy, with signal structure matched to real barcoding data, to quantify the feasibility of this procedure. We develop a new blind demixing approach to recover the barcodes that label each neuron, and validate this method on real data with known barcodes. We also develop a neural network which uses the recovered barcodes to reconstruct the neuronal morphology from the observed fluorescence imaging data, 'connecting the dots' between discontiguous barcode amplicon signals. We find that accurate recovery should be feasible, provided that the barcode signal density is sufficiently high. This study suggests the possibility of mapping the morphology and projection pattern of many individual neurons simultaneously, at high resolution and at large scale, via conventional light microscopy.

SUBMITTER: Chen S 

PROVIDER: S-EPMC9020678 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Blind demixing methods for recovering dense neuronal morphology from barcode imaging data.

Chen Shuonan S   Loper Jackson J   Zhou Pengcheng P   Paninski Liam L  

PLoS computational biology 20220408 4


Cellular barcoding methods offer the exciting possibility of 'infinite-pseudocolor' anatomical reconstruction-i.e., assigning each neuron its own random unique barcoded 'pseudocolor,' and then using these pseudocolors to trace the microanatomy of each neuron. Here we use simulations, based on densely-reconstructed electron microscopy microanatomy, with signal structure matched to real barcoding data, to quantify the feasibility of this procedure. We develop a new blind demixing approach to recov  ...[more]

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