The present invention provides assays and assay systems for use in spatially encoded biological assays. The invention provides an assay system comprising an assay capable of high levels of multiplexing where reagents are provided to a biological sample in defined spatial patterns; instrumentation capable of controlled delivery of reagents according to the spatial patterns; and a decoding scheme providing a readout that is digital in nature.

Methods and systems are provided herein for selecting an affinity reagent which binds a desired peptide epitope in a plurality of sequence contexts. The method relies on obtaining a peptide library, each peptide having the sequence X, wherein X is the desired peptide epitope, wherein each of a and 13 comprise an amino acid, using the peptide library to select an affinity reagent.

Methods and compositions for multiplexed protein-protein interaction profiling (e.g., immunoprofiling), based on nucleic acid tagging of polypeptides (e.g., by RNA display)are described. In some embodiments the described compositions and methods utilize a library of prey polypeptide targets linked to prey RNAs encoding them, and a population of bait polypeptides, e.g., a mixture of antibodies, that bind to one or more of the prey polypeptide targets and are used to isolate and identify the bound prey polypeptide targets by amplification of their associated prey RNAs and sequencing of the corresponding cDNAs. In other embodiments the prey polypeptide targets are linked to DNA Bar Codes, which serve as unique identifiers of the tagged polypeptide.

The present invention provides novel peptides (e.g., peptides, macrocyclic peptides, mini-proteins) that modulate protein-protein interactions or salts thereof, and methods of making and using the inventive peptides. In some embodiments, the peptides are high affinity inhibitors (e.g., K.sub.D of at most 100 nM, at most 10 nM, at most 1 nM) of a protein-protein interaction. In certain embodiments, these peptides interfere with p53-MDM2 binding interactions (e.g., by binding to MDM2 (GenBank Gene ID: 4193)). In some embodiments, the peptides interfere with the dimerization of the C-terminal domain of the human immunodeficiency virus (HIV) capsid protein (C-CA), comprising residues 146-231 of the HIV capsid protein (e.g., by binding to the C-terminal domain of the HIV capsid protein (C-CA), thereby inhibiting the dimeric interface of HIV capsid protein, thereby inhibiting viral assembly). These inventive peptides were rapidly generated and identified using novel methods described herein comprising combinatorial peptide synthesis and/or solution affinity selection.

Provided herein are methods of making and using disease-specific protein arrays. In particular, provided herein are embodiments of disease-specific protein arrays and their use in varied applications such as biomarker detection, diagnostics, elucidating signaling pathways, studying interaction networks and posttranslational modifications, and for drug discovery applications.

Provided herein are methods and compositions relating to libraries of optimized antibodies having nucleic acids encoding for an antibody comprising modified sequences. Libraries described herein include variegated libraries comprising nucleic acids each encoding for a predetermined variant of at least one predetermined reference nucleic acid sequence. Further described herein are protein libraries generated when the nucleic acid libraries are translated. Further described herein are cell libraries expressing variegated nucleic acid libraries described herein.

Provided are a composition for detecting protein-protein interactions comprising fragments of secreted alkaline phosphatase (SEAP) and a method for detecting protein-protein interactions using the same. According to the composition or the method of the present invention, it is possible to simply detect the protein-protein interactions in the cells without environmental changes (e.g., cell destruction) in the cells. Furthermore, the composition or the method of the present invention can also be used for detection of materials that enhance or inhibit protein-protein interactions.

Contemplated test kits and methods for food sensitivity are based on rational-based selection of food preparations with established discriminatory p-value. Particularly preferred kits include those with a minimum number of food preparations that have an average discriminatory p-value of 0.07 as determined by their raw p-value or an average discriminatory p-value of 0.10 as determined by FDR multiplicity adjusted p-value. In further contemplated aspects, compositions and methods for food sensitivity are also stratified by gender to further enhance predictive value.

The present invention provides assays and assay systems for use in spatially encoded biological assays. The invention provides an assay system comprising an assay capable of high levels of multiplexing where reagents are provided to a biological sample in defined spatial patterns; instrumentation capable of controlled delivery of reagents according to the spatial patterns; and a decoding scheme providing a readout that is digital in nature.

The present invention provides assays and assay systems for use in spatially encoded biological assays. The invention provides an assay system comprising an assay capable of high levels of multiplexing where reagents are provided to a biological sample in defined spatial patterns; instrumentation capable of controlled delivery of reagents according to the spatial patterns; and a decoding scheme providing a readout that is digital in nature.