Protein Sequence Recoding Into DNA for High-Throughput Proteomics
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Solution Overview
Problem
Current tools and technologies lack sensitivity, accuracy, and cost-effectiveness for unbiased characterization of proteomes, hindering early detection of aberrant protein sequences and concentrations associated with diseases like cancer.
Innovation Solution
A method involving chemically-reactive conjugates that recode amino acid sequences of peptides into DNA polymers, utilizing cycle and recode nucleic acids to determine identity and positional information through a series of immobilization, cleavage, and sequencing steps.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current tools and technologies are used for proteomic characterization, then the analysis can be performed with existing methods, but the sensitivity, accuracy, and cost-effectiveness are insufficient for unbiased characterization of proteomes
Solution Approach 1:
The patent introduces an intermediary conversion process that transforms protein sequences into DNA sequences through a recoding system. This intermediary step enables the use of highly sensitive and accurate DNA sequencing technologies to analyze proteomes, thereby achieving superior measurement precision while maintaining manageable system complexity through modular workflow design.
Solution Approach 2:
The patent creates a copied representation of protein sequences in the form of DNA sequences. By recoding amino acid sequences into corresponding DNA sequences, the method enables indirect analysis of proteomes using the well-established, high-precision DNA sequencing infrastructure, thus improving measurement precision without requiring direct development of new protein analysis technologies.
2Productivity
If traditional proteomic analysis methods are employed, then the workflow is relatively simple, but the throughput and ability to detect aberrant protein sequences is limited
Solution Approach 1:
The patent replaces traditional mechanical and chemical proteomic analysis methods with a biochemical recoding system followed by DNA sequencing. This substitution leverages the high-throughput capabilities of automated DNA sequencing technologies, dramatically increasing productivity and reducing analysis time compared to conventional proteomic approaches.
Solution Approach 2:
The patent fundamentally changes the analytical parameter from direct protein sequence analysis to DNA sequence analysis. By transforming the problem domain from proteomics to genomics, the method exploits the superior throughput and speed of DNA sequencing technologies, achieving high-productivity proteomic characterization.
3Productivity
If recoding amino acid sequences into DNA polymers is implemented, then highly-parallel and high-throughput analysis is achieved, but the device and process complexity increases
Solution Approach 1:
The patent segments the proteomic analysis process into distinct modular components: protein sample preparation, recoding reaction, DNA amplification, and sequencing. This segmentation allows each module to be optimized independently and facilitates high-throughput processing through parallelization, managing device complexity while maximizing productivity.
Solution Approach 2:
The patent employs universal recoding rules and standardized DNA sequences that can represent any amino acid sequence. This universality allows the same recoding system and infrastructure to analyze diverse proteomes, reducing the need for specialized equipment for each application and managing overall system complexity.
Data Source
AI summary
The present disclosure relates to compositions of matter, methods, and systems for analyzing polymeric macromolecules, including polymeric macromolecules such as peptides, polypeptides, and proteins.