Enhanced detection and quantitation of biomolecules
Inventors
Wilcox, Bruce • Swaminathan, Kavya • Williams, Preston B. • Deyarmin, Jared • Yang, Mi
Assignees
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Publication Number
US-12007397-B2
Publication Date
2024-06-11
Expiration Date
Abstract
Described herein are methods for screening for a disease state. The method may include obtaining multiple data sets, and identifying the disease state based on a combination of the data sets. The data sets may include biomolecule measurements obtained by multiple methods, such as through the use of particles and reference biomolecules.
Core Innovation
The invention relates to measuring endogenous biomolecules in a biological sample by forming biomolecule coronas on nanoparticles. A first aliquot of the biological sample is contacted with nanoparticles, thereby forming biomolecule coronas comprising endogenous biomolecules adsorbed directly to the nanoparticles, and the contacted sample is measured to obtain a first set of measurements.
To augment quantitation, a second aliquot of the biological sample is contacted with a plurality of reference biomolecules. The plurality of reference biomolecules comprises an isotopic label, a mass tag, a barcode, a post-translation modification, or a biomolecule from a species different than a species of a subject from whom the biological sample was taken, and the contacted sample is measured to obtain a second set of measurements.
The first and second sets of measurements are combined to support enhanced detection and quantification of biomolecules. The document further describes using multiple classifiers on one or more normalized or adjusted data sets and combining classifier outputs, for example by majority voting or weighted averaging, to improve classification of biological and disease states.
Claims Coverage
The partial content provides one independent claim. The main inventive coverage is the two-aliquot workflow using biomolecule corona measurement combined with reference biomolecules carrying isotopic labels, mass tags, barcodes, post-translation modifications, or different-species biomolecules.
Biomolecule corona formation on nanoparticles for endogenous biomolecules measurement
Contacting a first aliquot of the biological sample with nanoparticles to form biomolecule coronas comprising endogenous biomolecules adsorbed directly to the nanoparticles, and measuring the contacted sample to obtain a first set of measurements.
Reference biomolecules with isotopic labels, mass tags, barcodes, PTMs, or different-species biomolecules
Contacting a second aliquot of the biological sample with a plurality of reference biomolecules, where the plurality comprises an isotopic label, a mass tag, a barcode, a post-translation modification, or a biomolecule from a species different than a species of a subject from whom the biological sample was taken, and measuring to obtain a second set of measurements.
Combining endogenous corona measurements with reference biomolecule measurements
Combining the first and second sets of measurements to enable the measurement approach described by the claim.
Across the provided independent claim, the core coverage is achieved by measuring endogenous biomolecules captured as biomolecule coronas on nanoparticles from a first aliquot, measuring a second aliquot that is contacted with reference biomolecules bearing isotopic labels, mass tags, barcodes, post-translation modifications, or different-species biomolecules, and combining the resulting measurement sets.
Stated Advantages
Enhanced detection and quantification of biomolecules.
Accurate quantitation enabled by the reference biomolecules for normalization or adjustment to known concentrations.
Assessment of quality control metrics including mass accuracy and quantitative precision/accuracy, and quality of chromatographic performance and corona formation/digestion.
Contaminant biomolecule measurement for monitoring quality.
Improved classification of biological and disease states by combining outputs from multiple classifiers.
Improved cancer classification in examples using combined particle-based proteomic data and reference-standard-based quantitated proteomics and lipidomics.
Improved protein identification/quantitation using nanoparticle enrichment plus heavy-labeled internal standards, including rescuing low-abundance proteins and recovering false negatives or confirming true negatives.
Documented Applications
Disease-state screening and classification using normalized or adjusted multi-omic data sets, including cancers such as NSCLC.
Cancer example use cases reporting improved cancer classification by combining particle-based proteomic data with reference-standard-based quantitated proteomics and lipidomics.
Protein identification/quantitation using nanoparticle enrichment plus heavy-labeled internal standards, including rescuing low-abundance proteins and recovering false negatives or confirming true negatives.
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