Nucleic Acid Barcodes for Proteomic Variant Identification

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Solution Overview

Problem

Current methods for analyzing complex pools of genetic variants lack the ability to distinguish individual variants effectively, making it difficult to connect specific encoded molecular phenotypes with their corresponding genotypes.

Innovation Solution

The use of origin-specific nucleic acid barcodes allows for the high-throughput labeling and identification of target molecules, enabling the determination of their identity, quantity, and activity by sequencing, and associating genotype characteristics with phenotype characteristics while maintaining information about sample origin.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If high complexity pools of genetic variants are constructed, then the potential for exploration of design space is enormous, but the ability to distinguish individual variants and connect phenotypes with genotypes becomes difficult

Engineering Contradiction:
Improveexploration of design spaceVSAvoiddistinguishing individual variants
Core Design Contradiction:
Adaptability or versatilityVSDifficulty of detecting and measuring

Solution Approach 1:

The patent segments the complex pool of genetic variants into individually identifiable units by assigning unique nucleic acid barcodes to each variant. This segmentation allows high-throughput sequencing to distinguish and track individual variants throughout complex pools, resolving the contradiction between exploring diverse design spaces and maintaining the ability to detect specific variants.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces nucleic acid barcodes as intermediary molecules that mediate between genotype and phenotype detection. These barcodes serve as detectable proxies that can be sequenced to identify specific variants, enabling the connection between genetic design and molecular phenotype without directly observing the complex genetic structures.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If traditional methods are used to analyze complex genetic pools, then the analysis can be performed, but the process is expensive and laborious

Engineering Contradiction:
Improveanalysis capabilityVSAvoidanalysis efficiency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent replaces traditional mechanical and manual analysis methods with automated high-throughput nucleic acid sequencing. By substituting labor-intensive procedures with automated sequencing technology, the system maintains reliable analysis capability while dramatically improving productivity and reducing costs.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes the detection parameter from direct observation of complex genetic structures to sequencing of simple nucleic acid barcodes. This parameter change enables high-throughput automated analysis, transforming the process from expensive and laborious to efficient and scalable.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If individual variants are tracked through high-throughput sequencing, then multiplex analysis of diverse genotypes and phenotypes is enabled, but the complexity of the system increases

Engineering Contradiction:
Improvemultiplex analysis capabilityVSAvoidsystem complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent extracts the identification function from the complex genetic pool and concentrates it into simple nucleic acid barcodes. By taking out the essential identification capability and embedding it in these simple molecular tags, the system achieves high-throughput multiplex analysis while keeping the actual analysis process relatively simple despite the complexity of the biological system.

Inventive Principle:
Principle #2Taking out (Extraction)

Data Source

PatentUS20240254475A1Proteomic analysis with nucleic acid identifiers
Publication Date: 2024.08.01 THE BROAD INST INC
  • US20240254475A1 patent drawing
  • US20240254475A1 patent drawing
  • US20240254475A1 patent drawing

AI summary

The disclosure provides methods and compositions useful for labeling of target molecules with origin-specific nucleic acid identifiers (for example, barcodes), which can be used subsequently to identify, quantify, or otherwise characterize a feature or activity of target molecules originating from a particular discreet volume. Such target molecules can include polypeptides expressed by cells, in which nucleic acid molecules encoding the polypeptides are labeled with the same, or matched, origin-specific nucleic acid identifiers.