Disclosed are methods and systems for determining concentrations of a target molecule and a variant thereof in a sample. The sample can comprise or be suspected to comprise a target molecule and at least one variant thereof and is exposed to one or more recognition elements that bind to the target molecule and/or the at least one variant. A signal is detected that is associated with the binding of the target molecule and/or a signal is detected that is associated with the binding of the at least one variant to the one or more recognition elements. The concentration of the target molecule and/or the at least one variant thereof is determined based on the signals. The system can comprise a receiver adapted to receive a sample comprising or suspected to comprise a target molecule and the at least one variant thereof, the receiver comprising one or more recognition elements that bind to one or more epitopes in the target molecule and/or the at least one variant thereof.

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.

Immunoglobulin light chain proteins are used to generate synthetic fibrils in vitro. The fibrils are mixed with immunoglobulin light chain proteins from a biological sample. In either a direct binding assay, competition assay, or dilution-based competition assay, a signal is detected from the mixture. The intensity of the detectable signal relates to the level of binding between the immunoglobulin light chain proteins to the fibrils and can thus be used to identify amyloidogenic immunoglobulin light chain proteins in a biological sample of the subject and to assess amyloidogenic risk to a subject. For example, the signal intensities from the assays can be used in a comparison to one or more threshold (control) values derived from samples of known light chain types or in the absence of light chains. The comparisons permit identification of amyloidogenic proteins, assessment of amyloidogenic risk, and categorization of the subject into an appropriate “at risk” group.

Disclosed herein are isolated compositions including at least 2 of mutant peptides selected from the group consisting of SEQ ID NOS: 1-149, or polypeptides comprising the mutant peptides; wherein the composition comprises mutant peptides encoded by 2 or more genes. Also disclosed are methods for personalized treatment of breast cancer involving creating a peptide array of mutant peptides comprising the mutations in protein-encoding regions of the high-frequency cancer genes or the exome in a subject and screening the peptide array with a biological sample from the subject to detect antibodies in the biological sample that bind to the array, to detect antigenic targets for therapy in treating the subject.

Characterization of the binding dynamics at the interface between any two proteins that specifically interact plays a role in myriad biomedical applications. The methods disclosed herein provide for the high-throughput characterization of the specific interaction at the interface between two protein binding partners and the identification of functionally significant mutations of one or both protein binding partners. For example, the methods disclosed herein may be useful for epitope and paratope mapping of an antibody-antigen pair, which is useful for the discovery and development of novel therapies, vaccines, diagnostics, among other biomedical applications.

Provided herein are methods for determining presence of a target enzyme in a tissue section that include delivering a plurality of probes to a tissue section, where a probe of the plurality of probes comprises a capture agent that comprises a substrate for the target enzyme in the tissue section, and where the capture agent is conjugated to an oligonucleotide.

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.

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.

Provided herein engineered peptides that comprise a combination of spatially-associated topological constraints, wherein at least one constraint is derived from a reference target, and methods of selecting said engineered peptides. Further provided are methods of using the engineered peptides, including as positive and/or negative selection molecules in methods of screening a library of binding molecules.

The present invention provides compositions, systems, and methods for barcoding cells, beads, and secreted proteins in discrete entities (e.g. droplets) to allow sequencing data from such components that are separated during processing to be associated via the common barcodes. In some embodiments, the barcodes are tethered to the cell surface via a lipid, cholesterol, or antibody, or are attached to a surface molecule that moves from one cell to another via trogocytosis. In certain embodiments, such methods allow cell-cell interactions or secreted proteins in the discrete entity to be monitored.