Enhanced detection and quantitation of biomolecules

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.

What is claimed is: 
     
         1 . A classification method, comprising:
 (a) obtaining a first data set comprising first measurements of biomolecules adsorbed to particles from a first biological sample of a subject;   (b) obtaining a second data set comprising second measurements of the biomolecules of the first biological sample or of a second biological sample of the subject, wherein the second measurements comprise measurements of endogenous biomolecules normalized or adjusted based on measurements of internal standards of the biomolecules combined with the first biological sample or combined with the second biological sample, wherein the internal standards comprise a non-endogenous labeled version of the endogenous biomolecules, and wherein the second measurements are obtained with the first measurements or separately; and   (c) applying a classifier to evaluate a biological state in the subject using a combination of features from the first data set and the second data set.   
     
     
         2 . The method of  claim 1 , further comprising outputting or transmitting a report comprising information on the identified biological state. 
     
     
         3 . The method of  claim 1 , further comprising transmitting or outputting a recommendation of a treatment of the subject based on the identified biological state. 
     
     
         4 . The method of  claim 1 , wherein the subject is suspected of having the biological state. 
     
     
         5 . The method of  claim 1 , wherein the biological state comprises a disease state. 
     
     
         6 . The method of  claim 5 , wherein the disease state comprises cancer. 
     
     
         7 . The method of  claim 1 , wherein the biomolecules comprise proteins, lipids, metabolites, sugars, or nucleic acids. 
     
     
         8 . The method of  claim 1 , wherein the internal standards comprise an isotopic label, a mass tag, a barcode, a post-translation modification, or a biomolecule from a species different than a species of the subject. 
     
     
         9 . The method of  claim 1 , wherein the particles comprise nanoparticles. 
     
     
         10 . The method of  claim 1 , wherein the first biological sample or the second biological sample comprises a biofluid. 
     
     
         11 . A classification method, comprising:
 (a) obtaining a first data set comprising first measurements of biomolecules adsorbed to particles from a first biological sample of a subject;   (b) obtaining a second data set comprising second measurements of the biomolecules of the first biological sample or of a second biological sample of the subject, wherein the second measurements comprise measurements of endogenous biomolecules normalized or adjusted based on measurements of internal standards of the biomolecules combined with the first biological sample or combined with the second biological sample, wherein the internal standards comprise a non-endogenous labeled version of the endogenous biomolecules, and wherein the second measurements are obtained with the first measurements or separately;   (c) applying a first classifier to assign a first label corresponding to a biological state to the first data set;   (d) applying a second classifier to assign a second label corresponding to the biological state to the second data set; and   (e) combining the first label and the second label to obtain a combined label corresponding to the biological state.   
     
     
         12 . The method of  claim 11 , wherein the first or second measurements are obtained by measuring a readout indicative of an amount of the biomolecules. 
     
     
         13 . The method of  claim 11 , wherein (a) comprises contacting the first biological sample with the particles to adsorb the biomolecules to the particles, and measuring the adsorbed biomolecules. 
     
     
         14 . The method of  claim 11 , wherein (b) comprises combining the first biological sample or the second biological sample with the internal standards, measuring the internal standards with the biomolecules, and using the internal standards to obtain the second measurements. 
     
     
         15 . The method of  claim 11 , wherein the second measurements are obtained separately from the first measurements, in an aliquot or aliquant of the first biological sample. 
     
     
         16 . The method of  claim 11 , wherein the first and second labels comprise likelihoods or probabilities of the biological state, and wherein the method comprises averaging the likelihoods or probabilities. 
     
     
         17 . The method of  claim 11 , further comprising assigning weights to the first and second classifiers, thereby obtaining the weighted average, wherein the weights are assigned based on area under a ROC curve, area under a precision-recall curve, accuracy, precision, recall, sensitivity, F1-score, specificity, or a combination thereof. 
     
     
         18 . The method of  claim 11 , wherein the first and second classifiers err independently of one another with regard to the biological state. 
     
     
         19 . The method of  claim 11 , further comprising obtaining a third data set comprising measurements of a different type of biomolecules than the biomolecules of the first and second measurements; and using a third classifier to assign a third label corresponding to the biological state to the third data set; and wherein the combined label comprises a combination of the first label, the second label, and the third label. 
     
     
         20 . The method of  claim 11 , further comprising providing a treatment for the biological state to the subject when the combination label indicative of the biological state, and observing the subject without providing the treatment when the combination label is not indicative of the biological state.