Abstract: Systems and methods are provided for identifying a precursor ion without using any a priori precursor ion information. In one method, a sample is analyzed using a tandem mass spectrometer, producing at least one measured product ion spectrum from a precursor mass-to-charge ratio range. The at least one measured product ion spectrum are received. A subset of measured product ions is selected from the at least one measured product ion spectrum. A list of candidate compounds is created by searching a dictionary of potential compounds that includes one or more predicted product ions for each of the potential compounds using the subset of measured product ions. A candidate compound on the list is selected as the identified compound. In another method, the measured product ions are assumed to correspond to shortened forms of the peptide and a protein database is searched for shortened forms of the peptide.

Abstract: The invention generally relates to methods for analyzing a metabolite level in a sample. In certain embodiments, methods of the invention may involve obtaining a sample, analyzing the sample using a mass spectrometry technique to determine a level of at least one metabolite in the sample, and correlating the metabolite level with an originating source of the sample, thereby analyzing the sample.

Abstract: Reagents comprising MS active, fluorescent molecules with an activated functionality for reaction with amines useful in tagging biomolecules such as N-glycans and uses thereof are taught and described. In particular embodiments, the MS active, fluorescent molecules are of the compound of the Formula III or of the Formula IV where R1, R2 and R3 are defined herein.

Abstract: A method for analyzing aromatic compounds, and a reagent kit for LC-MS analysis of aromatic compounds. The method includes preparing a diazonium reagent, contacting aromatic compounds in a sample with the diazonium reagent to form an analyte; and measuring an amount or ratio of the analyte. The reagent kit includes a diazonium reagent, wherein the diazonium reagent includes (i) a diazonium salt that contains a diazonium ion; (ii) an amine and nitrous acid; and/or (iii) a nitrite and an acid.

Abstract: A method for determining an amino acid sequence of a polypeptide, including comprising: contacting a first sample containing the polypeptide with a first protease(e.g., Trypsin) to produce a first set of digested peptide fragments; fragmenting the first set of digested peptide fragments to produce a first set of fragmented peptide ions; determining masses of the first set of fragmented peptide ions; contacting a second sample containing the polypeptide with a second protease (e.g.

Abstract: This disclosure provides methods for quantifying individual amino acids in various bodily fluids obtained from a human patient. Also provided are reference ranges for normal amino acid levels in the various bodily fluids (e.g., blood plasma, urine, cerebrospinal fluid, and saliva) and for various age groups (e.g., neonates, infants, children, and adults).

Abstract: The present invention provides reagents for instrumentation quality control and methods of use thereof. In particular, sets of peptides or other molecules are provided for evaluating the performance of instruments with mass spectrometry (MS) and/or liquid chromatography (LC) functionalities.

Abstract: When a normal mass spectrometry is performed without dissociating an ion, the m/z range limitation voltage setting unit applies a radio-frequency voltage to each rod electrode of the quadrupole mass filter and controls the quadrupole voltage generator so as to apply a direct current voltage smaller than that at the time of ion selection for MS/MS spectrometry. When a small direct current voltage is applied, a mass scanning line is set so as to pass through a stability region on a Mathieu diagram over a long range, hence large m/z ions that do not fall within the stability region are blocked in the quadrupole mass filter. By adjusting a cut-off point on larger m/z side blocked in accordance with the measurement period of OA-TOFMS including the orthogonal accelerator, heavy ions that cause period delay are prevented from being introduced into the orthogonal accelerator.

Abstract: A method is for the simultaneous identification of one or more chemical compounds contained in a sample, from an analytical measurement of a pool of two or more of the samples. A measured intensity of a first and second signal is representative of an abundance of respectively the first and second chemical compound in the first sample, and a measured intensity of a third and fourth second signal is representative of an abundance of respectively a third and fourth chemical compound in the second sample. The first and third, and the second and fourth compound may be the same or different. The signal intensities are organized in a matrix aij of m columns and n rows, in which n is ?2 and corresponds to the number of chemical compounds in the pool, and m?2 and corresponds to the number of samples in the pool.

Abstract: This disclosure provides methods for quantifying individual amino acids in various bodily fluids obtained from a human patient. Also provided are reference ranges for normal amino acid levels in the various bodily fluids (e.g., blood plasma, urine, cerebrospinal fluid, and saliva) and for various age groups (e.g., neonates, infants, children, and adults).

Abstract: Buffer generators are described based on electrodialytic devices. The methods of using these devices can generate buffers for diverse applications, including separations, e.g., HPLC and ion chromatography. Also provided are chromatographic devices including the buffer generators, generally located upstream from a chromatography column, sample injector valve or both.

Abstract: Methods and systems for detecting allergens using mass spectrometry are provided herein. In some aspects, a sample can be screened for the presence or quantity of ovalbumin, lysozyme, casein (isoform S1 and S2), lactoglobulin, high and low glutens, wheat, rye, oats, barley, mustard, sesame, and various types of nuts including macadamia, pistachio, brazil, walnuts, peanuts and hazelnuts by detecting one or more peptides specific to the allergen of interest using selected MRM transitions.

Abstract: An external standard solution for use in the analysis of amino acid in plasma, containing, (1) at least one amino acid selected from the following components A, at a concentration of 0.0007 M to 0.49 M, and (2) (i) at least one amino acid selected from the following components B, at a concentration of 0.2 to 0.9 times of the lowest-concentration amino acid among the amino acids selected from components A, (ii) at least one amino acid selected from the following components C, at a concentration of 0.1 to 0.4 times of the lowest-concentration amino acid among amino acids selected from the components A, or (iii) at least one amino acid selected from the following components D, at a concentration of 0.05 to 0.

Abstract: Systems and methods for controlling the temperature of small volumes such as yoctoliter volumes, are described. The systems include one or more plasmonic nanostructures attached at or near a nanopore. Upon excitation of the plasmonic nanostructures, such as for example by exposure to laser light, the nanoparticles are rapidly heated thereby causing a change in the ionic conductance along the nanopore. The temperature change is determined from the ionic conductance. These temperature changes can be used to control rapid thermodynamic changes in molecular analytes as they interact with the nanopore.

Abstract: Mass spectrometry (MS) active, fluorescent rapid tagging reagent is provided having three substituent groups: (a) a tertiary amino group or other MS active atom; (b) a highly fluorescent moiety; and (c) a reactive group that can react with an amine. The reactive group provides rapid tagging of desired bio-molecules. The fluorescent moiety provides the fluorescent signal. The tertiary amino group provides the MS signal.

Abstract: Embodiments of a computer system, a method, and a computer-program product (e.g., software) for analyzing tandem-mass-spectrometry data are described. Using this analysis technique, unanticipated chemical modifications to peptides associated with proteins can be identified. In particular, a modification called a wild-card modification is used to identify the most likely chemical modifications in the peptides. A wild-card modification allows the addition of any mass, typically any integer atomic mass within a range, to any one amino acid residue within a candidate peptide.

Abstract: A separation system comprises (i) at least two separation units, each separation unit comprising a fluid inlet and a fluid outlet, wherein the separation units are connected in series outlet to inlet to form a line of separation units, and (ii) sensing and adjustment means, provided in-line between each separation unit, for continuously monitoring and adjusting at least one environmental property parameter of fluid flowing from one separation unit to a subsequent separation unit in the line of separation units. Uses of the separation system and a method for purification of a liquid containing a desired species, using separation units and in-line adjustment of a fluid flow or flows, are also disclosed.

Abstract: Systems and method for mass spectrometry are presented. In one embodiment, a method comprises: (a) acquiring one or more fragmentation signatures for a reference sample, wherein each fragmentation signature of the reference sample is acquired with a unique tandem mass spectrometry mode; (b) identifying one or more discriminate features across the plurality of fragmentation signatures of the reference sample; (c) acquiring one or more fragmentation signatures for an unknown sample, wherein each fragmentation signature of the unknown sample is acquired according to the discriminant features of step (b); (d) identifying one or more discriminate features across the plurality of fragmentation signatures of the unknown sample; (e) scoring the fragmentation signatures of step (c) by comparing the discriminate features of the reference sample, from step (b), against the discriminate features of the unknown sample, from step (d); and (f) identifying a structural isomer based on the score of step (e).

Abstract: A method for controlling the flow of liquid in a high performance liquid chromatography apparatus. The method includes operating a pump, measuring the liquid pressure downstream of the pump, measuring the liquid flow rate downstream of the pump, and controlling the operation of the pump. In the method, it is automatically determined whether the pump is controlled to achieve a desired pressure or controlled to achieve a desired flow rate. Fuzzy logic can be applied in the method to determine the switch between the control modes.

Abstract: Using NMR/MS based metabonomics and targeted lipidomics approaches the inventors have explored the metabolic phenotypes of aging and longevity in a cohort including centenarians, elderly and young adults. The inventors have identified biomarkers for a reduced risk of developing ageing related chronic inflammatory disorders and propose a method of diagnosing a lifestyle that allows delaying and/or avoiding ageing related chronic inflammatory disorders using PC-O 40:1 as biomarker.

Abstract: The present invention provides a method for the analysis of a compound with amino group (e.g., an amino acid or peptide) contained in a sample and convenient manner with a high sensitivity. The compound with amino group in a sample containing the compound with amino group is labeled with a specific carbamate compound such as p-trimethylammonium anilyl-N-hydroxysuccinimidyl carbamate iodide to enhance the selectivity and sensitivity. The present invention is preferably used in conjunction with mass spectrometry such as MS/MS method to facilitate quantitative analysis. The present invention further provides labeling reagents for mass spectrometry.

Abstract: The present invention generally relates to the field of biomarkers. In particular, the present invention relates to biomarkers such as PC-O 42:4 that can be used, for example for detecting and/or quantifying visceral adiposity and/or changes in visceral adiposity. This biomarker may also be used to diagnosing the effect of a change in lifestyle on visceral adiposity in a subject.

Abstract: The present invention generally relates to the field of biomarkers. In particular, the present invention relates to biomarkers such as PC-O 44:4 that can be used, for example for detecting and/or quantifying visceral adiposity and/or changes in visceral adiposity. This biomarker may also be used to diagnosing the effect of a change in lifestyle on visceral adiposity in a subject.

Abstract: The present invention generally relates to the field of biomarkers. In particular, the present invention relates to biomarkers such as PC-O 44:6 that can be used, for example for detecting and/or quantifying visceral adiposity and/or changes in visceral adiposity. This biomarker may also be used to diagnosing the effect of a change in lifestyle on visceral adiposity in a subject.

Abstract: The invention relates to antibody reagents that specifically bind to peptides carrying a ubiquitin remnant from a digested or chemically treated biological sample. The reagents allow the technician to identify ubiquitinated polypeptides as well as the sites of ubiquitination on them. The reagents are preferably employed in proteomic analysis using mass spectrometry. The antibody reagents specifically bind to the remnant of ubiquitin (i.e., a diglycine modified epsilon amine of lysine) left on a peptide which as been generated by digesting or chemically treating ubiquitinated proteins. The inventive antibody reagents' affinity to the ubiquitin remnant does not depend on the remaining amino acid sequences flanking the modified (i.e., ubiquitinated) lysine, i.e., they are context independent.

Abstract: The invention relates to antibody reagents that specifically bind to peptides carrying a ubiquitin remnant from a digested or chemically treated biological sample. The reagents allow the technician to identify ubiquitinated polypeptides as well as the sites of ubiquitination on them. The reagents are preferably employed in proteomic analysis using mass spectrometry. The antibody reagents specifically bind to the remnant of ubiquitin (i.e., a diglycine modified epsilon amine of lysine) left on a peptide which as been generated by digesting or chemically treating ubiquitinated proteins. The inventive antibody reagents' affinity to the ubiquitin remnant does not depend on the remaining amino acid sequences flanking the modified (i.e., ubiquitinated) lysine, i.e., they are context independent.

Abstract: A method is provided for producing motif-specific, context-independent antibodies that recognize a plurality of peptides or proteins within a genome that contain the same post-translationally modified motif. The method includes the step of immunizing a host with a degenerate peptide library antigen featuring (i) a fixed target motif containing one or more invariant amino acids including at least one modified amino acid, and (ii) a plurality of degenerate amino acids flanking the motif. Motif-specific, context-independent antibodies produced by the disclosed method are also provided. The method encompasses motifs consisting of a single modified amino acid, as well as short motifs comprising multiple invariant amino acids including one or more modified amino acids, such as all or part of kinase consensus substrate motifs, protein-protein binding motifs, or other cell signaling motifs. Methods of using the antibodies, e.g. for genome-wide profiling, are also provided.

Abstract: The invention provides an assay for assessing the conformational stability of a membrane protein, comprising: (a) providing a sample comprising a first population and a second population of a membrane protein; wherein the membrane protein in the first population is labelled with a donor label and the membrane protein in the second population is labelled with an acceptor label, or the membrane protein in the first population is labelled with an acceptor label and the membrane protein in the second population is labelled with a donor label, (b) exposing the first and second populations of the membrane protein to a stability modulating agent and/or condition, (c) and assessing aggregation between membrane proteins of the first and second populations by activating the donor label to permit a distance-dependent interaction with the acceptor label, which interaction produces a detectable signal.

Abstract: The present invention relates to a method for diagnosing cancer using information on the aberrant glycosylation of a glycoprotein involved in cancer progress. More particularly, the present invention relates to a cancer diagnosis peptide marker which is screened by the steps of: separating a glycoprotein aberrantly glycosylated according to the occurrence and progress of cancer from the blood of a lung cancer patient by using lectin; and selecting a marker peptide produced by the hydrolysis of the glycoprotein isolated by lectin. The marker peptide can be effectively used as a cancer diagnosis marker and for the diagnosis of cancer.

Abstract: The present disclosure provides peptide amino acid sequencing and identification methods and kits for performing such methods. For example, single-molecule detection of fluorophore-labeled peptides is disclosed using multiple rounds of standard Edman degradation or using digestion by chemicals or enzymes. Different fluorophores covalently attached to each of a specific type of amino acid side chain of a peptide provide for the derivation of the peptide's encoded amino acid sequence following image alignments of multiple Edman cycles or following digestion by chemicals or enzymes. The amino acid sequence of a peptide and/or the identity of the peptide can be determined by bioinformatic analysis based on the encoded amino acid sequence. The present disclosure further provides peptide derivatization and immobilization strategies to enable the sequencing and identification of a single peptide or a plurality of peptides.

Abstract: The invention provides compositions and methods for diagnosing a patient as having a myeloproliferative disease by identifying mutations in the MPL gene or gene products.

Abstract: This disclosure provides methods for quantifying individual amino acids in various bodily fluids obtained from a human patient. Also provided are reference ranges for normal amino acid levels in the various bodily fluids (e.g., blood plasma, urine, cerebrospinal fluid, and saliva) and for various age groups (e.g., neonates, infants, children, and adults).

Abstract: To provide an anti-cancer agent sensitivity determination marker, which marker can determine whether or not the patient has a therapeutic response to the anti-cancer agent, and novel cancer therapeutic means employing the marker. The anti-cancer agent sensitivity determination marker, the anti-cancer agent including oxaliplatin or a salt thereof and fluorouracil or a salt thereof, contains one or more substances selected from among an amino-acid-metabolism-related substance, a nucleic-acid-metabolism-related substance, a substance in the pentose phosphate pathway, a substance in the glycolytic pathway, a substance in the TCA cycle, a polyamine-metabolism-related substance, 7,8-dihydrobiopterin, 6-phosphogluconic acid, butyric acid, triethanolamine, 1-methylnicotinamide, NADH, NAD+, and a substance involved in the metabolism of any of these substances.

Abstract: The present invention provides liquid chromatography-mass spectrometry methods and kits for the specific, sensitive and rapid detection as well as quantitation of free amino acids in samples following High Pressure Liquid Chromatography (HPLC) separation.

Abstract: Unsymmetrical cyanine dyes that incorporate an aza-benzazolium ring moiety are described, including cyanine dyes substituted by a cationic side chain, monomeric and dimeric cyanine dyes, chemically reactive cyanine dyes, and conjugates of cyanine dyes. The subject dyes are virtually non-fluorescent when diluted in aqueous solution, but exhibit bright fluorescence when associated with nucleic acid polymers such as DNA or RNA, or when associated with detergent-complexed proteins. A variety of applications are described for detection and quantitation of nucleic acids and detergent-complexed proteins in a variety of samples, including solutions, electrophoretic gels, cells, and microorganisms.

Abstract: Techniques are described for performing mass spectrometry. A stream of one or more ions is generated. The stream is transmitted into a collision cell over a period of time. In accordance with a set of criteria including a retention time of one or more precursor ions, a collision energy of the collision cell is selected to generate one or more product ions for said one or more precursor ions in said stream.

Abstract: Disclosed are an apparatus and method for separation analysis of mannose-6-phosphate (M6P) by post-column fluorescence detection method. The apparatus is based on chromatography, and includes a column with a solid phase having affinity for phosphate, a flow path for the eluate, a heater installed on the flow path for M6P and a basic amino acid to react by heating the eluate in the flow path, and a fluorescence detector installed downstream of the heater for continuously irradiating the eluate with excitation light and measuring the intensity of the emission, and may include in the flow path a supply channel for addition of a basic amino acid between the column and the heater. The method is characterized in that it uses the apparatus and a second mobile phase consisting of a second buffer containing phosphate of predetermined concentration and adjusted to a predetermined pH.

Abstract: An analytical method of post-translational modifications in hemoglobin is disclosed. The analytical method comprises the steps of providing a blood comprising the hemoglobin with post-translational modification of nitration, nitrosylation, or oxidation; performing an extraction process to the blood by an organic solvent; quantifying the hemoglobin by a fluorescent spectrometry; hydrolyzing the hemoglobin into a plurality of peptides by an enzyme; and using a nanoflow liquid chromatography-nanospray ionization tandem mass spectrometry to characterize and quantify the post-translational modifications of the hemoglobin.

Abstract: Disclosed herein are markers for diagnosing Alzheimer's Disease and/or mild cognitive impairment, for predicting risk of developing Alzheimer's Disease and/or mild cognitive impairment, and for monitoring the efficacy of treatment for Alzheimer's Disease and/or mild cognitive impairment. Also disclosed herein are methods of diagnosing Alzheimer's Disease and/or mild cognitive impairment in a subject in need thereof, for predicting risk of developing Alzheimer's Disease and/or mild cognitive impairment in a subject in need thereof, and for monitoring the efficacy of a treatment for Alzheimer's Disease and/or mild cognitive impairment in the subject.

Abstract: A reagent includes a magnetic nanoparticle, a cleavable linker, and a primary amine reactive group. A first end of the cleavable linker may conjugate to a surface of the magnetic nanoparticle. A second end of the cleavable linker may conjugate to a primary amine reactive group. A method of using the reagent includes adding the reagent to a native protein mixture such that magnetic nanoparticles may conjugate to the protein with exposed primary amine groups in the native protein mixture. The method also includes separating the proteins with exposed primary amine group from other components of the native protein mixture under a magnetic field. The method further includes removing the magnetic nanoparticles from the proteins with the exposed primary amine groups from at cleavable linkers. The method finally includes identifying sequences and/or sites of the exposed primary amine groups in the proteins.

Abstract: Provided herein are methods of diagnosing Alzheimer's disease (“AD”) based on characteristic changes of the levels of certain free amino acids or dipeptides (collectively termed as “AD diagnosis markers”) in the body fluid sample of an individual, carnosine synthesis activities in the plasma, and dopamine synthesis activities in the plasma. Also provided are methods of simultaneously determining the levels of at least two free amino acids or dipeptides in the biological fluid sample of an individual.

Abstract: The present disclosure provides methods an compositions for the detection of plant exposure to plant pathogens. The methods relate to determining the identity of peptides isolated from the surface of plant starch granules.

Abstract: A method (100) for analyzing chemicals includes fractionating a complex sample into at least two sample portions that each includes potions of two polypeptides though in different concentration ratios, digesting and performing LC/MS on each of the sample portions (110, and associating precursor ions observed via LC/MS with their corresponding polypeptide in response to LC/MS provided intensity data (170). A set of precursor ions that has substantially similar intensity ratios in both sample portions is determined to be associated with the same polypeptide.

Abstract: Described herein are high-throughput methods of monitoring D-serine levels in plasma. The assay involves the use of strong cation solid phase extraction (SPE) to isolate D-serine from plasma, followed by quantitation of D-serine using the D-amino acid oxidase- (DAAO-) catalyzed reaction. Also described are methods of screening for compounds that act as DAAO inhibitors.

Abstract: A clickable cross-linker compound provides an easily scanned reporter ion for effective and efficient cross-linking and identification of intermolecular and intramolecular interactions of proteins and peptides.

Abstract: This invention relates to methods and compositions for detection and treatment of neurodegenerative diseases. In particular, the invention relates to polypeptides that can protect against neuron degeneration, nucleic acid molecules that encode such polypeptides, and antibodies that recognize said polypeptides.

Abstract: The present invention pertains to the field of toxicological assessments for risk stratification of chemical compounds. Specifically, it relates to a method for diagnosing increased peroxisomal proliferation. It also relates to a method of determining whether a compound is capable of inducing such peroxisomal proliferation in a subject and to a method of identifying a drug for treating increased peroxisomal proliferation. Furthermore, the present invention relates to a data collection comprising characteristic values of at least five metabolites, a data storage medium comprising said data collection, and a system and a device for diagnosing increased peroxisomal proliferation. Finally, the present invention pertains to the use of a group of metabolites or means for the determination thereof for the manufacture of a diagnostic device or composition for diagnosing increased peroxisomal proliferation in a subject.

Abstract: Reagents comprising MS active, fluorescent molecules with an activated functionality for reaction with amines useful in tagging biomolecules such as N-glycans and uses thereof are taught and described.

Abstract: The present invention relates to the use of fish skin as novel industrial source of collagen. Advantageously, said skin is obtained after the filleting or cutting of the fresh fish and frozen immediately after filleting/cutting, thus guaranteeing a very good quality of the base material, both from the bacteriological standpoint and from the standpoint of the native property of the protein.

Abstract: The present invention generally relates methods for analyzing agricultural and/or environmental samples using liquid bridges. In certain embodiments, the invention provides a method for analyzing an agricultural sample for a desired trait including obtaining a gene or gene product from an agricultural sample, in which the gene or gene product is in a first fluid; providing a liquid bridge for mixing the gene or gene product with at least one reagent to form a mixed droplet that is wrapped in an immiscible second fluid; and analyzing the mixed droplet to detect a desired trait of the agricultural sample.