A method of solvent-induced protein precipitation (SIP) for detecting the interaction of ligands with proteins in a complex protein sample. After the equal amount of solvent is added to the protein samples with and without a ligand to denature and precipitate the proteins, the protein abundances in supernatant and/or precipitate in the ligand group and the control group are measured by quantitative technology. The target protein(s) of a ligand is/are determined by comparing the differences of protein abundances in the ligand group and the control group. The affinity between a ligand and its targets can be evaluated by dose dependent experiments. This method does not require the chemical modification of the ligand and has the feature of high specificity. Furthermore, in certain embodiments, the targets identified by SIP method are complementary to those identified by thermal proteome profiling (TPP) method.

Methods for the large scale identification of post-translational modification states of proteins and enzyme activities for carrying out post-translational modification reactions involve the analysis of functional extracts from fresh and frozen samples using protein arrays. The methods and kits of the present invention can be used to analyze and characterize compounds for their effects on post-translational modifications and their pathways. The methods and kits can also be used to diagnose and characterize a wide variety of diseases and medical conditions, including cancer, neurodegenerative diseases, immune diseases, infectious diseases, genetic diseases, metabolic conditions, and drug effects using cells or body fluids of a patient.

A method of mass spectrometry determines if a mutated variant of a target protein is present in a sample. The method includes subjecting the sample to fragmentation so as to cause the target protein to fragment to form second generation fragment ions, and then mass analysing these fragment ions to obtain spectral data. The method determines if a mutated variant is present in the sample by determining that an ion in the spectral data has a mass to charge ratio that differs from the mass to charge ratio of an ion that would be observed if the target protein was a normal unmutated version of the target protein, and by an amount that corresponds to a mass difference that would be caused by the target protein being a mutated variant of the target protein.

The method presented herein includes acquiring a mass spectrum of a molecule that includes mass spectrum peaks corresponding to a precursor ion and fragment ions. The method also includes identifying at least a portion of the fragment ions in the mass spectrum as corresponding to one or more monomer subunit ion of the precursor ion by appending one or more of the fragment ions to an inferable constituent to produce a topology building block. The topology building block is then stored in a candidate pool as corresponding to one or more of the monomer subunit ion if the combined mass of the inferable constituent and one or more of the fragment ions satisfy a first user-defined mass tolerance. One or more candidate topology of the precursor ion is then obtained by combining a plurality of the topology building blocks that satisfy a second user-defined mass tolerance for the precursor ion.

Bead arrays suitable for analysis by mass spectrometry are disclosed. In an embodiment, a bead array includes multiple reactive sites, each of the reactive sites being capable of binding multiple distinct target analytes.

The present invention provides methods to improve the sensitivity of detecting glycosylamines released from glycoconjugates, such as glycoproteins or glycopeptides, by enzymatic digestion when labeling them with amine-reactive dyes.

Provided is a sensitive and specific LC-MS-MRM quantification method that distinguishes outer-arm and core fucosylated configurations of N-glycopeptides. Advantage is taken of limited fragmentation of the glycopeptides at low collision energy (collision-induced dissociation) CID to produce linkage-specific Y-ions. These ions are selected as multiple reaction monitoring (MRM) transitions for the quantification of the outer-arm and total fucosylation of 23 glycoforms of 9 glycopeptides in 7 plasma proteins. The method permits quantification of the glycoforms directly in plasma or serum without fractionation of samples or glycopeptide enrichment. A pilot study of fucosylation in liver cirrhosis of hepatitis C vims (HCV) and non-alcoholic steatohepatitis (NASH) etiologies demonstrated that liver cirrhosis is consistently associated with increased outer-arm fucosylation of a majority of the analyzed proteins. The outer-arm fucosyaltion of the A2G2F1 glycoform of the VDKDLQSLEDILHQVENK peptide of fibrinogen was found to increase more than 10-fold in the cirrhosis patients compared to healthy controls.

The present disclosure provides a system comprising a communication interface and computer for assigning a label to the biomolecule fingerprint, wherein the label corresponds to a biological state. The present disclosure also provides a sensor arrays for detecting biomolecules and methods of use. In some embodiments, the sensor arrays are capable of determining a disease state in a subject.

Described herein are systems and methods for analyzing biological samples. Including a method for processing an analyte, comprising providing a fluidic device comprising the analyte and one or more polymer precursors; selecting a discrete area within said fluidic device; providing an energy source in optical communication with fluidic device; and selectively supplying a unit of energy generated from the energy source to the fluidic device to generate a polymer matrix within the fluidic device, wherein the polymer matrix is within the discrete area or adjacent to the discrete area.

Described herein are systems and methods for analyzing biological samples. Including a method for processing an analyte, comprising providing a fluidic device comprising the analyte and one or more polymer precursors; selecting a discrete area within said fluidic device; providing an energy source in optical communication with fluidic device; and selectively supplying a unit of energy generated from the energy source to the fluidic device to generate a polymer matrix within the fluidic device, wherein the polymer matrix is within the discrete area or adjacent to the discrete area.