Peptide Array Biomarker Identification via Proteome Segmentation

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Solution Overview

Problem

Current methods are inadequate for identifying candidate biomarkers for autoimmune diseases and infections, as they fail to efficiently differentiate between various health conditions and disease activities through antibody binding patterns.

Innovation Solution

The use of peptide arrays to identify discriminating peptides that differentiate between autoimmune diseases and healthy conditions by aligning peptides to proteins in a proteome, obtaining protein scores, and ranking them for statistical significance, thereby identifying candidate biomarkers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If large-scale comparative interrogation of the human proteome is performed, then insights into disease biology and biomarker discovery are improved, but the complexity and resource requirements of the analysis increase

Engineering Contradiction:
Improvebiomarker identification accuracyVSAvoidproteome analysis complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The proteome is segmented into individual protein entries from the Uniprot database, allowing systematic comparison of protein sequences across different disease states. This segmentation enables the complex proteome analysis to be broken down into manageable units that can be processed and compared individually

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Discriminating peptides serve as intermediaries between the complex proteome data and the final biomarker identification. These peptides are derived from protein sequences and used as queries to identify proteins that differentiate between disease states, simplifying the overall analysis pipeline

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If discriminating peptides are used to differentiate autoimmune diseases from healthy conditions, then diagnostic accuracy is improved, but the computational methods and analysis time increase

Engineering Contradiction:
Improvedisease differentiation accuracyVSAvoidbiomarker identification time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

Peptide sequences are pre-derived from protein sequences in the Uniprot database before the actual disease differentiation analysis. This preliminary preparation of peptide queries allows for faster comparison and identification during the actual biomarker discovery process, reducing analysis time while maintaining accuracy

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The method employs statistical parameters such as p-values and area under the ROC curve to quantify differentiation accuracy. By changing and optimizing these statistical thresholds, the method achieves high reliability in disease differentiation while managing computational resources efficiently

Inventive Principle:
Principle #35Parameter changes

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

This approach effectively identifies candidate biomarkers that can differentiate between autoimmune diseases and healthy conditions, predicting disease occurrence and activity with high accuracy, as demonstrated by area under the receiver operator characteristic (ROC) curve values ranging from 0.60 to 1.00.

Implementation Method 1

identifying a set of discriminating peptides bound to antibodies in the biological sample from the plurality of subjects that differentiate the autoimmune disease from at least one different health condition

Methodology Applied
Scientific EffectAntibody binding:

Data Source

PatentUS11371990B2Methods for identifying candidate biomarkers
Publication Date: 2022.06.28 COWPER SCI INC
  • US11371990B2 patent drawing
  • US11371990B2 patent drawing
  • US11371990B2 patent drawing

AI summary

The disclosed embodiments concern methods, devices, and systems for identifying candidate biomarkers useful for the diagnosis, prognosis, monitoring and screening and/or as targets for the treatment of diseases and conditions in subjects, in particular autoimmune and infectious diseases. The identification of candidate biomarkers is predicated on identifying discriminating peptides present on a peptide array, which can distinguish samples from different subjects having different health conditions by the binding patterns of antibodies present in the samples.