Proteoform Analysis Using Iterative Affinity Reagent Probing
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Solution Overview
Problem
Existing technologies lack the ability to comprehensively characterize and quantify proteoforms at high throughput and high sensitivity, failing to provide adequate diagnostic or prognostic precision in biological systems.
Innovation Solution
Methods and systems for analyzing proteoforms involve immobilizing individual protein molecules on solid supports, using a library of affinity reagents to identify and characterize proteoforms based on specific modifications, and employing iterative probing and detection techniques to determine the presence and abundance of different proteoforms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If existing protein analysis technologies (mass spectrometry, sequencing) are used, then protein presence and quantity can be detected, but they lack the ability to comprehensively characterize and quantify proteoforms at high throughput and high sensitivity
Solution Approach 1:
The patent segments the proteome analysis into distinct functional modules: (1) protein extraction and preparation, (2) immobilization on solid supports, (3) iterative probing with affinity reagents, (4) signal detection, and (5) data processing. This segmentation enables each module to be optimized independently, achieving both high throughput and high precision proteoform characterization that neither mass spectrometry nor sequencing could achieve alone.
2Loss of information
If genomic or transcriptomic analysis is performed, then biological system information can be obtained, but the data are proxies that provide inadequate diagnostic or prognostic precision for actual biological functions
Solution Approach 1:
The patent replaces indirect genomic/transcriptomic proxies with direct proteomic measurement. Instead of inferring biological function from DNA or RNA data, the system directly detects and quantifies actual protein molecules and their proteoforms in the biological system, eliminating information loss between genotype and phenotype while managing complexity through standardized assay protocols.
3Loss of information
If protein analysis focuses on presence and quantity only, then simple quantification is achieved, but it fails to capture the functional diversity caused by post translational modifications and splice variants
Solution Approach 1:
The patent employs dynamic, iterative probing where affinity reagents are applied in multiple sequential rounds to detect different proteoform characteristics. The system adapts the probing sequence based on detected modifications, enabling comprehensive characterization of proteoform diversity (phosphorylation, glycosylation, truncation, etc.) while maintaining operational simplicity through automated cycling of standardized reagent applications.
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
The described methods enable sensitive and reproducible characterization and quantification of proteoforms, providing a more accurate understanding of biological system functions and potential diagnostic or therapeutic insights.
Implementation Method 1
using a library of affinity reagents to identify and characterize proteoforms based on specific modifications
Data Source
AI summary
Methods, reagents, kits and systems for analyzing different proteoforms of proteins of interest are provided. The provided methods, systems, etc. provide detection, characterization and quantitation of proteoforms for different biologically relevant proteins for monitoring and characterizing biological processes.