The present invention relates to methods and products associated with in vivo enzyme profiling. In particular, the invention relates to methods of in vivo processing of exogenous molecules followed by detection of signature molecules as representative of the presence of active enzymes associated with diseases or conditions. The invention also relates to products, kits, and databases for use in the methods of the invention.

The invention relates to a method for determining the presence of at least one distinct polypeptide in a biological sample comprising contacting the biological sample with a hydrolyzing agent, wherein the hydrolyzing agent is capable of hydrolyzing the distinct polypeptide in a sequence-specific manner such that at least one distinct peptide having a predetermined peptide measured accurate mass would result if the at least one distinct polypeptide were present in the biological sample, to obtain a hydrolyzed sample; bringing the hydrolyzed sample in contact with a substrate comprising at least one immobilized binding partner, wherein the at least one immobilized binding partner is capable of specifically binding the distinct peptide; removing the hydrolyzed sample from the substrate in a manner such that the distinct peptide would remain bound to the immobilized binding partner; contacting the substrate with an elution solution, wherein the distinct peptide would dissociate from the immobilized binding partner into the elution solution; subjecting a portion of the elution solution to liquid chromatography to segregate a plurality of molecules in the portion of the elution solution to obtain sorted molecules; determining the measured accurate mass of at least one sorted molecule present in the elution solution; and determining the presence of the at least one distinct polypeptide in the biological sample when a measured accurate mass of at least one molecule is substantially equal to the predetermined peptide measured accurate mass.

Methods are disclosed to detect, characterize, measure, and quantify human and humanized antibodies, and their conjugates, that may be present in pre-clinical animal biological samples, or human biological samples, including plasma/serum and tissue samples.

A system and method for intra-operative sample analysis including acquiring a tissue sample, preparing the tissue sample for mass spectrometry imaging, conducting a mass spectrometry imaging procedure on the tissue sample to produce an image, and analyzing the image to determine the presence or absence of a bio-marker.

A method and an apparatus for determining a concentration of a target analyte in a sample of bodily fluid are disclosed. The method involves providing a sample of bodily fluid including the target analyte, providing an internal standard solution including a mixture of components having a plurality of isotopes of the target analyte, wherein a concentration of each isotope is unknown, adding the internal standard solution to the sample, analyzing the sample including the internal standard solution using a mass spectrometer, creating a sample function curve based on signal intensities, wherein the signal intensities define arbitrary units, transferring an analyte signal into a corresponding arbitrary analyte unit by means of the sample function curve, and transferring the arbitrary analyte unit into the concentration of a target analyte by means of a standardization function representing a curve of concentrations depending on the arbitrary units.

Disclosed herein is a system and methods for determining the alleles, neoantigens, and vaccine composition as determined on the basis of an individual's tumor mutations. Also disclosed are systems and methods for obtaining high quality sequencing data from a tumor. Further, described herein are systems and methods for identifying somatic changes in polymorphic genome data. Finally, described herein are unique cancer vaccines.

The invention provides an unbiased method to assess the binding of a test compound to a multiplicity of proteins in the same sample, including samples from living cells by applying the unbiased determination technique of SWATH-MS or the biased technique of SRM-MS to a thermal shift assay to evaluate drug target interactions. In addition, the results created by SWATH-MS can be analyzed by SRM-MS in a biased manner to assess the binding of a test compound to a multiplicity of proteins in the same sample, including samples from living cells.

A multiplex proteome quantification method based on isobaric dimethyl labeling implements dimethyl labeling of peptide N-terminal in an acidic condition and C-terminal in an alkaline condition one after another by means of Hall the property that a dimethylation reaction has different rates on an amino group at the peptide N-terminal and an amino group on a Lysine side chain at the peptide C-terminal in the acidic condition. Multiplex labeling of peptide samples is implemented by means of the organic combination of various isotope forms of a dimethyl labeling reagents. The mass-to-charge ratios in MS1 of peptides after multiplex labeling are completely the same, the mass-to-charge ratios of the fragment ions in MS2 are different, and multiplex quantitative analyses are carried out by extracting the intensity values of corresponding fragment ions in the MS2.

A method for diagnosis of IgA nephropathy is provided using a combination of alpha-1B-glycoprotein (A1BG) or a truncated fragment thereof having a molecular weight of 13-60 kDa, orosomucoid 1 (ORMI), and Ig lambda-2 chain C regions (IGLC2) as protein markers in a urine sample from a subject.

A method includes applying distinct isobaric tags to each of a plurality of samples; combining the samples; performing a separation of species within the combined samples; isolating and fragmenting labeled parent ions within a m/z range to produce a plurality of reporter ions, each reporter ion corresponding to one of the isobaric tags; determining intensities of the plurality of reporter ions and ions representative of a parent species at a plurality of points along a peak; and fitting the intensity of the ions representative of a parent species and the plurality of reporter ions at the plurality of points to obtain a relative abundance of the parent species in each of the plurality of samples.