Method to Connect Chromatin Accessibility and Transcriptome
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Solution Overview
Problem
Existing methods for simultaneously measuring chromatin accessibility and RNA expression in single cells are limited by scalability issues and material loss, necessitating laborious separation steps that hinder high-throughput analysis.
Innovation Solution
A micro-droplet based protocol using a splint oligo to capture chromatin accessible regions and mRNA from the same single cells with barcoded oligo-dT beads, enabling concurrent characterization of epigenetic regulation and transcriptome profiles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If manual separation of materials into individual tubes is used for multi-omics measurement, then chromatin accessibility and RNA expression can be measured in single cells, but scalability is greatly limited and material loss occurs
Solution Approach 1:
The patent combines chromatin accessibility measurement (ATAC-seq) and RNA expression measurement (scRNA-seq) into a single unified protocol called SNARE-seq. Both measurements are performed simultaneously in the same single cells using a micro-droplet based approach, eliminating the need for manual separation into individual tubes. This merging enables high-throughput processing while maintaining single-cell resolution for both omics types.
Solution Approach 2:
The patent introduces a splint oligo as an intermediary molecular component that facilitates the simultaneous capture of chromatin accessible regions and mRNA. The splint oligo acts as a bridge that allows both ATAC-seq and scRNA-seq measurements to occur in the same micro-droplet without requiring physical separation of materials, thereby enabling high-throughput processing.
2Measurement precision
If manual separation of materials into individual tubes is used for multi-omics measurement, then chromatin accessibility and RNA expression can be measured in single cells, but material loss is significant due to limited starting material
Solution Approach 1:
The patent combines chromatin accessibility measurement (ATAC-seq) and RNA expression measurement (scRNA-seq) into a single unified protocol called SNARE-seq. Both measurements are performed simultaneously in the same single cells using a micro-droplet based approach, eliminating the need for manual separation into individual tubes. This merging enables high-throughput processing while maintaining single-cell resolution for both omics types.
3Measurement precision
If separation steps are performed for multi-omics measurement, then chromatin accessibility and RNA expression can be measured, but laborious separation steps hinder high-throughput analysis
Solution Approach 1:
The patent combines chromatin accessibility measurement (ATAC-seq) and RNA expression measurement (scRNA-seq) into a single unified protocol called SNARE-seq. Both measurements are performed simultaneously in the same single cells using a micro-droplet based approach, eliminating the need for manual separation into individual tubes. This merging enables high-throughput processing while maintaining single-cell resolution for both omics types.
Solution Approach 2:
The patent extracts and removes the laborious separation steps from the multi-omics measurement process. By using a micro-droplet based approach where both chromatin and RNA are captured simultaneously in the same droplets, the protocol eliminates the need for manual separation into individual tubes, thereby simplifying the workflow and enabling high-throughput analysis.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables high-throughput, simultaneous measurement of chromatin accessibility and RNA expression in single cells without material separation, providing comprehensive insights into cellular heterogeneity and epigenetic control.
Implementation Method 1
a splint oligo is used to allow the capture of chromatin accessible regions, as well as mRNA from the same single cells
Implementation Method 2
mRNA from the same single cells by barcoded oligo-dT beads
Data Source
AI summary
The invention provides scalable methods for measuring chromatin accessibility and RNA expression in the same single cells by connecting chromatin accessibility and transcriptome.