System, assay and method for partitioning proteins

Abstract

The present disclosure provides a system comprising a communication interface and computer for assigning a label to the biomolecule fingerprint, wherein the label corresponds to a biological state. The present disclosure also provides a sensor arrays for detecting biomolecules and methods of use. In some embodiments, the sensor arrays are capable of determining a disease state in a subject.

1 . A method for identifying a potential biomarker from a plurality of biological samples, comprising:
 (a) providing a plurality of biological samples comprising a plurality of proteins in the plurality of biological samples, wherein a first subset of biological samples in the plurality of biological samples is associated with a first biological state, and a second subset of biological samples in the plurality of biological samples is associated with a second biological state;   (b) incubating the plurality of biological samples with a plurality of particles to form a plurality of protein coronas on the plurality of particles;   (c) performing mass spectrometry using the plurality of protein coronas to generate a plurality of protein identifications and a plurality of protein levels;   (d) determining (i) a first difference in the presence of a protein identification in the plurality of protein identifications between the first subset of biological samples and the second subset of biological samples and (ii) a second difference in a protein level in the plurality of protein levels between the first subset of biological samples and the second subset of biological samples; and   (e) identifying the first difference, the second difference, or both as the potential biomarker when the first difference, the second difference, or both are statistically significant.   
     
     
         2 . The method of  claim 1 , wherein the determining comprises determining (i) the first difference in the presence of at least two protein identifications in the plurality of protein identifications between the first subset of biological samples and the second subset of biological samples and (ii) the second difference in at least two protein levels in the plurality of protein levels between the first subset of biological samples and the second subset of biological samples. 
     
     
         3 . The method of  claim 1 , wherein the first biological state comprises a cancerous state and the second biological state comprises a non-cancerous state, wherein the first biological state comprises a first type of cancer and the second biological state comprises a second type of cancer, or wherein the first biological state comprises an early-stage cancer state and the second biological state comprises a late-stage cancer state. 
     
     
         4 . The method of  claim 1 , wherein the plurality of biological samples comprises a third subset of biological samples associated with a third biological state, and wherein the determining comprises determining the first difference and the second difference between the first subset of biological samples, the second subset of biological samples, and the third subset of biological samples. 
     
     
         5 . The method of  claim 1 , wherein the plurality of particles comprises at least 2 particle types comprising different physicochemical properties. 
     
     
         6 . The method of  claim 5 , wherein the plurality of protein identifications and the plurality of protein levels are stratified based on a particle type of the at least 2 particle types. 
     
     
         7 . The method of  claim 1 , wherein the mass spectrometry comprises liquid chromatography-tandem mass spectrometry (LC-MS/MS). 
     
     
         8 . The method of  claim 1 , wherein the first subset of biological samples and the second plurality of subset samples comprise at least 10 samples, and wherein the plurality of protein identifications comprise at least 100 protein identifications. 
     
     
         9 . The method of  claim 1 , wherein a protein identification in the plurality of protein identifications comprises an identification of a proteolytically fragmented peptide. 
     
     
         10 . The method of  claim 1 , wherein the mass spectrometry generates a plurality of MS spectra, and the plurality of protein identifications are generated by searching a database to match the plurality of MS spectra to the plurality of protein identifications. 
     
     
         11 . A computer-implemented method for identifying a potential biomarker from a plurality of biological samples, comprising:
 (a) providing a dataset comprising:
 (i) a first plurality of protein identifications and a first plurality of protein levels for a first plurality of biological samples associated with a first biological state; and 
 (ii) a second plurality of protein identifications and a second plurality of protein levels for a second plurality of biological samples associated with a second biological state; 
   (b) determining using a machine learning algorithm, (i) a first difference in the presence of a protein identification between the first plurality of protein identifications and the second plurality of protein identifications, and (ii) a second difference in a protein level between the first plurality of protein levels and the second plurality of protein levels; and   (c) identifying the first difference, the second difference, or both as the potential biomarker when the difference is statistically significant.   
     
     
         12 . The computer-implemented method of  claim 11 , wherein the determining comprises determining (i) the first difference in at least two protein identifications between the first plurality of protein identifications and the second plurality of protein identifications and (ii) the second difference in at least two protein levels between the first plurality of protein levels and the second plurality of protein levels. 
     
     
         13 . The computer-implemented method of  claim 11 , wherein the first biological state comprises a cancerous state and the second biological state comprises a non-cancerous state, wherein the first biological state comprises a first type of cancer and the second biological state comprises a second type of cancer, or wherein the first biological state comprises an early-stage cancer state and the second biological state comprises a late-stage cancer state. 
     
     
         14 . The computer-implemented method of  claim 11 , wherein the dataset comprises a third plurality of protein identifications and a third plurality of protein levels for a third plurality of biological samples associated with a second biological state, wherein the determining comprises (i) determining the first difference in the presence of the protein identification between the first plurality of protein identifications, the second plurality of protein identifications, and the third plurality of protein identifications, and (ii) determining the second difference in the protein level between the first plurality of protein levels, the second plurality of protein levels, and the third plurality of protein levels. 
     
     
         15 . The computer-implemented method of  claim 11 , wherein the plurality of protein identifications and the plurality of protein levels are stratified based on a particle type of at least 2 particle types. 
     
     
         16 . The computer-implemented method of  claim 11 , wherein the first plurality of biological samples and the second plurality of biological samples comprise at least 10 samples, and wherein the first plurality of protein identifications and the second plurality of protein identifications comprise at least 100 protein identifications. 
     
     
         17 . A method for identifying a potential biomarker from a plurality of biological samples, comprising:
 (a) providing a plurality of biological samples comprising a plurality of proteins in the plurality of biological samples, wherein a first subset of biological samples in the plurality of biological samples is associated with a first biological state, and a second subset of biological samples in the plurality of biological samples is associated with a second biological state;   (b) incubating the plurality of biological samples with a plurality of sensor elements to adsorb a plurality of proteins on the plurality of sensor elements;   (c) performing mass spectrometry using the plurality of proteins to generate a plurality of protein identifications and a plurality of protein levels;   (d) determining (i) a first difference in the presence of a protein identification in the plurality of protein identifications and (ii) a second difference in a protein level in the plurality of protein levels between the first subset of biological samples and the second subset of biological samples; and   (e) identifying the first difference, the second difference, or both as the potential biomarker when the first difference, the second difference, or both are statistically significant,
 wherein the first subset of biological samples and the second subset of biological samples comprise at least 10 samples, 
 and wherein the plurality of protein identifications comprises at least 100 protein identifications. 
   
     
     
         18 . The method of  claim 17 , wherein the plurality of sensor elements comprises at least 2 sensor element types comprising different physicochemical properties. 
     
     
         19 . The method of  claim 18 , wherein the plurality of protein identifications and the plurality of protein levels are stratified based on a sensor element type of the at least 2 sensor element types. 
     
     
         20 . The method of  claim 19 , wherein a protein identification in the plurality of protein identifications comprises an identification of a proteolytically fragmented peptide.