Compound arrays for sample profiling

Abstract

The invention provides arrays of compound for use in profiling samples. The arrays include compounds bind to components of the samples at relatively low affinities. The avidity of compounds binding to components of the samples can be increased by forming arrays such that multivalent components of the samples (e.g., antibodies or cells) can bind to more than one molecule of a compound at the same time. When a sample is applied to an array under such conditions, the compounds of the array bind to component(s) of the sample with significantly different avidities generating a profile characteristic of the sample.

1 - 86 . (canceled) 
     
     
         87 . A method of therapeutic intervention in a patient diagnosed with an autoimmune disease, the method comprising:
 (a) contacting a sample with a peptide array, wherein:
 (i) said sample comprises a mixture of antibodies; and 
 (ii) said peptide array comprises a plurality of peptides having different amino acid sequences, each one of said peptides occupying different features of the array; 
   (b) detecting a binding of the mixture of antibodies to the peptide array to form a binding profile, wherein the binding profile is the aggregate binding of the mixture of antibodies to the peptide arrays; and   (c) comparing, by a computer system, said binding profile detected in (b) to a binding profile associated with the autoimmune disease, wherein the comparing analyzes binding interactions with dissociation constants of between 1 mM and 1 μM, and wherein the patient is diagnosed with the autoimmune disease when said binding profile detected in (b) reflects changes in the concentrations of at least two antibodies in the mixture of antibodies as compared with said binding profile associated with the autoimmune disease; and   (d) identifying a patient diagnosed with the autoimmune disease that would benefit from a therapeutic intervention.   
     
     
         88 . The method of  claim 87 , wherein a therapeutic intervention is administered to the patient diagnosed with the autoimmune disease. 
     
     
         89 . The method of  claim 87 , wherein said autoimmune disease is lupus. 
     
     
         90 . The method of  claim 87 , wherein said at least two antibodies bind with different degrees of promiscuity to at least two said peptides having different amino acid sequences. 
     
     
         91 . The method of  claim 87 , wherein said peptide array has at least 10,000 peptides. 
     
     
         92 . The method of  claim 87 , wherein said plurality of peptides are between 8-35 amino acids long. 
     
     
         93 . The method of  claim 87 , wherein said comparison of (c) is performed by a computer system that measures differences between different patterns of antibody binding by a Spearman Correlation. 
     
     
         94 . The method of  claim 87 , wherein said peptides are spotted onto a surface of the array. 
     
     
         95 . The method of  claim 87 , wherein said peptides are synthesized onto a surface of the array. 
     
     
         96 . The method of  claim 87 , wherein said sample is a blood sample. 
     
     
         97 . The method of  claim 87 , wherein said different peptides are between 8 and 20 residues in length. 
     
     
         98 . The method of  claim 87 , wherein said changes are within three orders of magnitude of the mean plus three standard deviations of a binding strength of empty features in the array. 
     
     
         99 . The method of  claim 88 , wherein autoantigens or peptides thereof are identified on the array. 
     
     
         100 . The method of  claim 99 , wherein the patient diagnosed with the autoimmune disease is treated with identified autoantigens or peptides thereof. 
     
     
         101 . The method of  claim 100 , wherein the therapeutic intervention induces tolerance of the autoimmune disease. 
     
     
         102 . A method for therapeutic intervention in a subject predicted to develop a disease, the method comprising:
 (a) contacting antibodies in a blood sample from the subject at risk of developing a disease with an array comprising at least 10,000 different peptides immobilized on a surface of the array and occupying a distinct feature, wherein each distinct feature comprises peptides of a same sequence, and wherein at least 50 of the different peptides have dissociation constants of between 1 mM and 1 μM to at least one antibody in each of the blood samples;   (b) detecting a pattern of antibody binding of the blood sample from said subject to the immobilized different peptides in the array, wherein the pattern comprises binding interactions with dissociation constants of between 1 mM and 1 μM;   (c) comparing the pattern of antibody binding obtained in step (b) to a reference pattern of antibody binding comprising binding interactions with dissociation constants of between 1 mM and 1 μM obtained from reference sample from subjects known to have said disease; and   (d) identifying a plurality of peptides common to the pattern of antibody binding obtained in step (b) for the subject at risk for said disease to the reference pattern of antibody binding obtained in step (c) for the reference samples thereby predicting the development of said disease in the subject.   
     
     
         103 . The method of  claim 102 , further comprising administering a therapeutic intervention to the subject identified at risk for said disease. 
     
     
         104 . The method of  claim 102 , wherein the subject at risk for developing the disease is asymptomatic for the disease. 
     
     
         105 . The method of  claim 102 , wherein the disease is cancer. 
     
     
         106 . The method of  claim 105 , wherein the cancer is selected from pancreatic cancer, glioma, breast cancer, and sarcoma. 
     
     
         107 . The method of  claim 102 , wherein the disease is organ rejection following organ transplant. 
     
     
         108 . The method of  claim 102 , wherein the disease is an infectious disease. 
     
     
         109 . The method of  claim 102 , wherein the peptides have sequences of between 8-35 amino acids. 
     
     
         110 . The method of  claim 102 , wherein the peptides are spotted on the array. 
     
     
         111 . The method of  claim 102 , wherein the peptides are synthesized in situ on the array. 
     
     
         112 . The method of  claim 102 , wherein sequences of the peptides immobilized on the array are chosen without regard to the identity of a particular target or natural ligand to the target. 
     
     
         113 . The method of  claim 102 , wherein the pattern of antibody binding is obtained from a blood sample of less than 1 μl. 
     
     
         114 . The method of  claim 102 , wherein the blood sample is plasma or serum. 
     
     
         115 . The method of  claim 102 , wherein the pattern of antibody binding is detected by an isotype of the antibody. 
     
     
         116 . The method of  claim 102 , wherein steps (c) and (d) are performed by a computer system that measures differences between different binding patterns of antibody binding by a Spearman Correlation. 
     
     
         117 . A method for therapeutic intervention in a subject predicted to develop a viral or bacterial infectious disease, the method comprising:
 (a) contacting antibodies in a blood sample from the subject at risk of developing the infectious disease with an array comprising at least 10,000 different peptides immobilized on a surface of the array and occupying a distinct feature, wherein each distinct feature comprises peptides of a same sequence, and wherein at least 50 of the different peptides have dissociation constants of between 1 mM and 1 μM to at least one antibody in each of the blood samples;   (b) detecting a pattern of antibody binding of the blood sample from said subject to the immobilized different peptides in the array, wherein the pattern comprises binding interactions with dissociation constants of between 1 mM and 1 μM;   (c) comparing the pattern of antibody binding obtained in step (b) to a reference pattern of antibody binding comprising binding interactions with dissociation constants of between 1 mM and 1 μM obtained from reference sample from subjects known to have said infectious disease; and   (d) identifying a plurality of peptides common to the pattern of antibody binding obtained in step (b) for the subject at risk for said infectious disease to the reference pattern of antibody binding obtained in step (c) for the reference samples thereby predicting the development of said infectious disease in the subject.   
     
     
         118 . The method of  claim 117 , further comprising administering a therapeutic intervention to the subject identified at risk for said infectious disease.