The present invention provides methods and systems for identifying and classifying patterns comprising the T cell exposed motifs and the frequencies of such motifs in collections of proteins that make up the human proteome, immunoglobulinome, T cell receptor repertoire or microbiome, and other proteomes of environmental of microbial origin, or subsets thereof. It further provides graphical representations that facilitate comparisons of T cell exposed motif patterns between samples or between time points. The present invention also provides methods and systems for identifying and classifying patterns in repertoires of cells including receptor bearing cells and cells of tissue samples and detecting patterns of utility in diagnosis and monitoring of health and disease.

The invention provides methods, reagents and systems for incorporating non-natural amino acids into proteins, preferably in vivo, using the endogenous protein synthesis machinery of an organism. The incorporated non-natural amino acids contain reactive groups for further chemical reagents, which may serve as a “handle” to enrich the proteins or fragments thereof in a number of uses, such as proteomic analysis, imaging of diseased tissues/cells, etc.

Cells produce electrophilic products with the potential to modify and affect the function of proteins. Chemoproteomic methods have provided a means to qualitatively inventory proteins targeted by endogenous electrophiles; however, ascertaining the potency and specificity of these reactions to identify the most sensitive sites in the proteome to electrophilic modification requires more quantitative methods. Here, we describe a competitive activity-based profiling method for quantifying the reactivity of electrophilic compounds against 1000+ cysteines in parallel in the human proteome. Using this approach, we identify a select set of proteins that constitute “hot spots” for modification by various lipid-derived electrophiles, including the oxidative stress product 4-hydroxynonenal (HNE). We show that one of these proteins, ZAK kinase, is labeled by HNE on a conserved, active site-proximal cysteine, resulting in enzyme inhibition to create a negative feedback mechanism that can suppress the activation of JNK pathways by oxidative stress.

The invention discloses a method for measurement of peptidic degradation products of a proteolytic cascade in biological samples, especially blood samples, wherein the sample is incubated until a steady state equilibrium is reached for at least one peptidic degradation product involved in said proteolytic cascade and wherein said at least one peptidic degradation product in steady state equilibrium of the proteolytic cascade is quantified in the sample.

The present invention provides a method of quantifying the activity of a protein modifying enzyme in a sample, comprising calculating the value K for said protein-modifying enzyme on the basis of the number of modified peptides in a sample that are substrates of said protein modifying enzyme, the intensity of the modified peptides, each modified peptide in the sample that is a substrate of said protein modifying enzyme, the total number of modified peptides in the sample, the intensity of the modified peptides and all of the modified peptides in the sample. A method of quantifying the activity of a protein modifying enzyme in a sample, comprising calculating the value SC for said protein-modifying enzyme on the basis of a reduction in proliferation using an inhibitor at an inhibitor concentration at which proliferation is measured and the “in vitro” IC50i of the inhibitor against a primary target is also provided. The invention further provides methods of identifying inhibitors with which to treat a patient, methods of treatment, a computer readable medium, a computer program product and devices for carrying out the methods.

The invention provides a method of identifying a peptide interaction site on a target protein wherein the target protein modulates the phenotype of a mammalian cell, using mammalian encoded peptides (SEPs) such as short open reading frame (sORF) encoded peptides. The invention further provides a method for the identification of new therapeutic targets and protein interaction sites for use in drug discovery.

Disclosed are methods and systems for the quantification of AngI and/or determination of plasma renin activity in a sample. The methods and systems disclosed herein can be useful for diagnosis of hypertension, aldosteronism and other abnormalities of the renin angiotensin aldosterone system (RAAS).

This disclosure comprises devices and methods for determining the identity of individual protein molecules in a complex mixture by unfolding the protein into a polypeptide, tagging selected residues on the polypeptide with selected oligonucleotide sequence tags that recognize selected residues on said polypeptide, and then detecting the oligonucleotide sequence tags.

In shotgun proteomics, generally only a fraction of peptides from a parent protein are actually detected. Because a large portion of the protein sequence is not detected, it is often impossible to determine whether the expressed protein is present in a modified, spliced, or truncated form. Provided herein are methods and systems for analyzing polypeptides which allow for the increase of the mean sequence coverage of a protein concomitant with bioinformatics analysis in order to distinguish putative proteoforms with improved amino acid resolution. Aspects of the invention include (1) a deep sequencing strategy to provide more protein sequence coverage than is typically achieved, and (2) a computational approach to view protein expression across its full length and identify regions of the protein that are potentially subject to such regulation. This technology has global utility in proteomics and will be of particular use for the analysis of biosimilar protein drug therapeutics.

Disclosed herein are methods and compounds for profiling a lysine reactive protein. Also described herein are methods, compounds, and compositions for identifying a small molecule fragment ligand that interacts with a reactive lysine residue.