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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 08, 2022
- Source ID
- 10.1371/journal.pcbi.1009991
Entities
People
- Jackson Loper
- Liam Paninski
- Pengcheng Zhou
- Shuonan Chen
Organizations
- Asia-Pacific Network for Global Change Research
- Intelligence Advanced Research Projects Activity
- National Institutes of Health