Methods and systems for identifying and/or quantifying polypeptide binding interactions of ligand-binding polypeptides are disclosed. Detailed methods include methods for identifying binding ligands of ligand-binding polypeptides and methods for assessing changes in binding behavior due to alterations of ligand-binding polypeptides. Detailed systems include array-based systems that permit detection of ligand binding interactions at single-analyte resolution.

Described herein are methods for screening for a disease state. The method may include obtaining multiple data sets, and identifying the disease state based on a combination of the data sets. The data sets may include biomolecule measurements obtained by multiple methods, such as through the use of particles and reference biomolecules.

A method of diagnosing non-alcoholic fatty liver disease (NAFLD) in a subject, and/or determining the stage of NAFLD in a subject diagnosed with NAFLD; or a method of identifying a subject having an increased risk of developing liver cancer; or a method of treating a subject with NAFLD having advanced fibrosis or cirrhosis; wherein the method comprises determining the level of at least one steroid hormone or metabolite thereof in a urine sample provided by the subject.

The invention mainly relates to the mass spectrometric identification of pathogens in blood cultures from bloodstream infections (septicemia). The invention provides a method with which microbial pathogens can be separated in purified form from blood after a relatively brief cultivation in a blood culture flask, without any interfering human proteins or any residual fractions of blood particles such as erythrocytes and leukocytes, and can be directly identified by mass spectrometric measurement of their protein profiles. The method is based on the use of relatively strong tensides to destroy the blood particles by dissolving the weak cell membranes and most of the internal structures of the blood particles; in spite of the fact that tensides are regarded as strong ionization inhibitors in MALDI and other ionization processes required for mass spectrometric measurements. This method allows unknown pathogens to be obtained in their pure form by centrifuging or filtration and to be identified on the taxonomic level of species or subspecies. Problems with DNA from high levels of leukocytes can be resolved by special measures. After sufficient cultivation, the identification in a mass spectrometric laboratory takes only half an hour.

Disclosed herein is a method for verifying the primary structure of a protein through comparative analyses between ion clusters observed in mass spectra and a series of simulated ion clusters deduced from its putative chemical formula. The method comprises the steps of: preparing a protein sample for mass spectrometric analyses; collecting mass spectra of the protein sample; obtaining master ion cluster from a plurality of ion clusters in the mass spectra; producing a series of simulated ion clusters according to the chemical formula of the protein; finding the best fit for the master ion cluster among the series of simulated ion clusters; and verifying if said best-fit simulated ion cluster corresponds to the chemical formula of the protein.

The present disclosure provides azetidine compounds of Formula I and their pharmaceutically acceptable salts, their compositions, and methods for their use in determining azetidine compound binding to proteins. The azetidine compounds are useful as probes, for monitoring diacylglycerol kinase activity, and for identifying druggable targets.

Provided herein are methods for preparing biological samples for spatial proteomic analysis, methods of determining a location of a protein analyte in a biological sample, and methods of determining a location of a protein analyte and a nucleic acid analyte in a biological sample.

Systems and methods to identify new protein targets of a chemical compound or its derivatives were described. The methods can be used for detection of new binding partners as long as the chemical compound can covalently bind to the protein targets. Once protein targets are resolved, information related to new protein targets can then be used to couple with real-world patient data such as adverse events, efficacy data, and disease correlation data to deduce real-world evidence. Systems collectively with all this information can aide clinical development and use of pharmaceutical drug. Methods are provided for detection of covalently bound phenyl vinyl sulfone (PVS) or its derivatives, and afatinib or its derivatives. Furthermore, generation of antiserum recognizing carrier bound PVS or carrier bound afatinib is described. PRMT1 is described as a new target of PVS and RRM1, RRM2, and NFKB are described as new targets of afatinib.

Described herein are methods such as multi-omic methods for assessing a disease such as cancer. The multi-omic methods may integrate proteomic, transcriptomic, genomic, lipidomic, or metabolomic data. The method screening diseases or disease states. Also described herein are methods for screening for diseases or disease states from biological samples. The methods may include assessing whether a nodule, mass, or cyst is cancerous.

The present invention provides markers for judging the efficacy of therapy with a PD-1 signal inhibitor before or at an early stage of the therapy. As biomarkers for predicting or judging the efficacy of therapy with a PD-1 signal inhibitor, surrogate indicators of metabolic changes relating to mitochondrial activity in T cells and/or T cell activation in a subject are used. As such indicators, intestinal flora-related metabolites in the serum or plasma, energy metabolism-related metabolites in the serum or plasma, amino acid metabolism-related metabolites and/or derivatives thereof in the serum of plasma, oxygen consumption rate and/or ATP turnover in peripheral blood CD8.sup.+ cells, amino acids in T cells, and T-bet in peripheral blood CD8.sup.+ cells may be used.