Spatial Barcode Mapping for Single-Cell Transcriptome Analysis
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Solution Overview
Problem
Current single cell analysis methods fail to preserve the positional context of cells within tissues, leading to a loss of intra-tissue factors that influence cellular function and state.
Innovation Solution
A method of labeling cells with unique barcode constructs that denote their spatial location within a tissue, allowing for single cell analysis techniques like scRNA-Seq to be paired with tissue-level contextual information, enabling the elucidation of local environmental effects on cell state and mapping intra-tissue processes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If tissue dissociation into isolated cells is performed for single cell analysis, then single cell transcriptome profiling is enabled, but cell positional context is lost
Solution Approach 1:
The patent applies preliminary action by labeling cells with spatial barcodes before tissue dissociation. The method involves incorporating oligonucleotide barcodes into the extracellular matrix at specific spatial locations prior to breaking down the tissue into single cells. This ensures that when cells are later isolated, they retain information about their original positions through the barcodes that were pre-established in the tissue architecture.
Solution Approach 2:
The patent uses an intermediary approach by introducing oligonucleotide barcodes as a mediator between the tissue structure and single cell analysis. These barcodes serve as informational intermediaries that bridge the gap between the physical tissue architecture and the dissociated single cell suspension, allowing positional information to be transferred and preserved through the dissociation process without directly maintaining the intact tissue structure.
2Productivity
If bulk or population analysis is performed on dissociated cells, then single cell analysis can be conducted, but intra-tissue factors cannot be resolved
Solution Approach 1:
The patent applies segmentation by dividing the tissue into spatially distinct regions, each marked with unique oligonucleotide barcodes. This segmentation allows the tissue to be analyzed at single-cell resolution while simultaneously preserving information about which spatial segment each cell originated from, thereby enabling both high-throughput single cell analysis and resolution of intra-tissue factors.
Solution Approach 2:
The patent implements local quality by assigning different oligonucleotide barcode sequences to different spatial locations within the tissue. This creates a localized informational signature for each region, allowing cells to be identified and analyzed according to their specific microenvironmental context, thereby resolving intra-tissue factors while maintaining analytical throughput.
Data Source
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AI summary
Methods of tagging cells with unique oligonucleotide "zipcode" constructs are provided. By these methods and associated compositions, cells in a multicellular structure such as a tissue section can be tagged with a construct, the unique composition of which is associated with the cells position in the multicellular structure. Subsequently, the multicellular structure can be dissociated into single cells and a single cell transcriptome analysis performed, as well as other types of single cell analyses. By preserving positional information in the analyzed single cells, biological processes within the tissue can be mapped. By these methods, the effects of the local environment surrounding a cell on its state and various functions can be elucidated, and intra-tissue processes can be mapped and observed. Likewise, coordinated actions by multiple cells within a tissue can be mapped and tracked over time.