Nucleic Acid Recording Tags for Multiplexed Proteome Interaction Readout
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Solution Overview
Problem
Current proteomics analysis methods lack the throughput and parallelization necessary to effectively capture the dynamic and complex information contained in protein molecules, limiting our understanding of proteome dynamics in health and disease.
Innovation Solution
A method involving immobilization of proteins with recording tags and coding tags on a support, allowing for information transfer and generation of extended recording and coding tags through ligation or polymerase-mediated reactions, enabling high-throughput analysis of protein interactions and modifications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional proteomics analysis methods are used, then analysis can be performed with current technology, but throughput and parallelization are insufficient to capture dynamic protein information
Solution Approach 1:
The invention segments the proteomics analysis process by immobilizing individual proteins on solid supports and associating each with unique recording tags and coding tags. This segmentation enables parallel processing of multiple proteins simultaneously, dramatically increasing throughput while maintaining manageable system complexity through modular organization
Solution Approach 2:
The invention introduces recording tags and coding tags as intermediary elements that mediate between proteins and detection systems. These tags enable high-throughput analysis by providing standardized interfaces for information transfer, allowing complex protein interactions to be captured and read out efficiently without directly complicating the core protein analysis system
2Loss of information
If proteins are analyzed in detail to capture dynamic information, then understanding of proteome dynamics improves, but the complexity and difficulty of detection increases
Solution Approach 1:
The invention creates information copies by associating recording tags with proteins and coding tags with interacting molecules. These tag copies serve as surrogates that capture interaction information without requiring direct observation of complex protein-protein or protein-ligand interactions, thereby reducing detection difficulty while preserving information
Solution Approach 2:
The invention performs preliminary actions by pre-immobilizing proteins on solid supports and pre-associating recording tags with proteins before interactions occur. This preparation enables subsequent interactions to be detected more easily, as the system is already configured to capture information without requiring complex real-time analysis setup
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, multiplexed analysis of proteomes, capturing extensive protein information for better understanding of health and disease states, facilitating precision medicine.
Implementation Method 1
allowing transfer of information between (i) the recording tag associated with each protein that binds and/or reacts with the small molecule(s), peptide(s) or peptide mimetic(s), peptidomimetic(s) (e.g., peptoid(s), β-peptide(s), or D-peptide peptidomimetics), polysaccharide(s), or aptamer(s) of one or more agents, and (ii) the coding tag of the one or more agents, to generate an extended recording tag and/or an extended coding tag
Data Source
AI summary
Methods and Kits for analyzing macromolecules, including peptides, polypeptides, and proteins, employing nucleic acid encoding are disclosed. The sample analysis kits employ nucleic acid encoding and/or nucleic acid recording of a molecular interaction and/or reaction, such as recognition events (e.g., between an antigen and an antibody, between a modified terminal amino acid residue, or between a small molecule or peptide therapeutic and a target, etc.). Assays that do not require the cyclic transfer of information between a coding tag and a recording tag are also disclosed, including single cycle assays.