Abstract: A Liquid Chromatography Mass Spectrometry system comprises: a chromatograph; a mass spectrometer configured to ionize separated fractions of a sample received from the chromatograph; and a programmable processor operable to repeatedly execute the steps of: (i) causing the mass spectrometer to perform a data-independent analysis of the precursor ion species using a mass analyzer of the mass spectrometer; (ii) calculating one or more degree-of-matching scores that relate to detection of an internal standard; and (iii) if each of the degree-of-matching scores meets a respective degree-of-matching condition, performing a quantitative tandem mass spectrometric analyses of both the internal standard and the analyte; the programmable processor further operable to calculate a quantity of the analyte in the sample by comparison between intensities of one or more mass spectral signals generated by the quantitative tandem mass spectrometric analyses of the analyte and the internal standard.

Abstract: A Liquid Chromatography Mass Spectrometry system comprises: a chromatograph; a mass spectrometer configured to ionize separated fractions of a sample received from the chromatograph; and a programmable processor operable to repeatedly execute the steps of: (i) causing the mass spectrometer to perform a data-independent analysis of the precursor ion species using a mass analyzer of the mass spectrometer; (ii) calculating one or more degree-of-matching scores that relate to detection of an internal standard; and (iii) if each of the degree-of-matching scores meets a respective degree-of-matching condition, performing a quantitative tandem mass spectrometric analyses of both the internal standard and the analyte; the programmable processor further operable to calculate a quantity of the analyte in the sample by comparison between intensities of one or more mass spectral signals generated by the quantitative tandem mass spectrometric analyses of the analyte and the internal standard.

Abstract: A method for determining a quantity of an analyte in a liquid sample, comprises: adding a known quantity of an internal standard comprising an isotopically labeled version of the analyte to the sample; (b) providing a continuous stream of the sample having the internal standard to an inlet of a Liquid Chromatography Mass Spectrometry (LCMS) system; and repeatedly performing the steps of: performing a data-independent analysis of the precursor ion species using a mass analyzer, whereby mass spectra of a plurality of fragment-ion species are acquired; calculating one or more degree-of-matching scores that relate to either a number of ions of the internal standard that overlap between results of the data-independent analysis and tabulated mass spectral data of the internal standard; and performing quantitative tandem mass spectrometric analyses of the internal standard and the analyte if each of the degree-of-matching scores meets a respective degree-of-matching condition.

Abstract: A method for determining a quantity of an analyte in a liquid sample, comprises: adding a known quantity of an internal standard comprising an isotopically labeled version of the analyte to the sample; (b) providing a continuous stream of the sample having the internal standard to an inlet of a Liquid Chromatography Mass Spectrometry (LCMS) system; and repeatedly performing the steps of: performing a data-independent analysis of the precursor ion species using a mass analyzer, whereby mass spectra of a plurality of fragment-ion species are acquired; calculating one or more degree-of-matching scores that relate to either a number of ions of the internal standard that overlap between results of the data-independent analysis and tabulated mass spectral data of the internal standard; and performing quantitative tandem mass spectrometric analyses of the internal standard and the analyte if each of the degree-of-matching scores meets a respective degree-of-matching condition.

Abstract: A variable data dependent acquisition/dynamic exclusion (vDDA/DE) method selects target m/z range utilizing a MS1 precursor topography map over the most recently acquired MS spectrum to identify the precursor m/z values and MS/MS acquisition parameters to improve the selection of the next data-dependent MS/MS acquisition. The topography used to define the next set of DDA scan events is defined by previous tandem MS scan events defined by precursor quadrupole isolation windows as well as all detected compounds contained within the specific tandem MS events. At least some of the parameters used for MS/MS data acquisition are dynamic so as to exhaustively sample the user specified MS mass range with MS/MS information. These parameters include the quadrupole MS isolation width and symmetry around the targeted m/z value. Using this approach, a greater proportion of the precursor m/z space is effectively and efficiently sampled per chromatographic peak width.

Abstract: Methods of isolating nucleic acid and protein molecules from a single formalin-fixed, paraffin-embedded (FFPE) tissue sample section include lysing the cells of the tissue sample section, alkylating, reducing, and enzymatically digesting proteins in the lysate, and separating nucleic acids present in the lysate from the digested proteins. Cell lysis is performed under conditions that permit extraction of DNA, RNA, and proteins that are suitable for genomic and proteomic analysis. In particular, the buffer conditions, reaction time, and temperature of the lysis reaction are such that a suitable amount of DNA, RNA, and proteins are released and in stable condition for separation and proteogenomic analysis. Systems for performing methods include reagents and apparatus for performing steps of the method. Panels for detecting the presence and level of expression of peptides to differentiate between disease states include a plurality of peptides.

Abstract: A variable data dependent acquisition/dynamic exclusion (vDDA/DE) method selects target m/z range utilizing a MS1 precursor topography map over the most recently acquired MS spectrum to identify the precursor m/z values and MS/MS acquisition parameters to improve the selection of the next data-dependent MS/MS acquisition. The topography used to define the next set of DDA scan events is defined by previous tandem MS scan events defined by precursor quadrupole isolation windows as well as all detected compounds contained within the specific tandem MS events. At least some of the parameters used for MS/MS data acquisition are dynamic so as to exhaustively sample the user specified MS mass range with MS/MS information. These parameters include the quadrupole MS isolation width and symmetry around the targeted m/z value. Using this approach, a greater proportion of the precursor m/z space is effectively and efficiently sampled per chromatographic peak width.

Abstract: Methods and systems for rapid prediction and/or confirmation of antimicrobial susceptibility of a microorganism using top-down mass spectrometry, ion-ion chemistry, and a database with susceptibility, pathogenicity and antimicrobial resistance markers for sample characterization.

Abstract: Methods are described for monitoring the amounts of PTH variants in a biological sample by digesting the sample to produce surrogate peptides specific to the targeted PTH variants, and detecting and quantifying the surrogate peptides by selective reaction monitoring (SRM) mass spectrometry, using a set of precursor-to-product ion transitions optimized for sensitivity and selectivity. The PTH variants, or a portion thereof, may be concentrated in the sample by means of immunoaffinity capture or other suitable technique. The mass spectrometric method described herein enables the concurrent measurement of peptides representative of a plurality of targeted PTH variants in a single assay.

Abstract: Methods are described for monitoring the amounts of PTH variants in a biological sample by digesting the sample to produce surrogate peptides specific to the targeted PTH variants, and detecting and quantifying the surrogate peptides by selective reaction monitoring (SRM) mass spectrometry, using a set of precursor-to-product ion transitions optimized for sensitivity and selectivity. The PTH variants, or a portion thereof, may be concentrated in the sample by means of immunoaffinity capture or other suitable technique. The mass spectrometric method described herein enables the concurrent measurement of peptides representative of a plurality of targeted PTH variants in a single assay.

Abstract: Immunogenic Escherichia coli O157:H7 (0157) proteins expressed during infection of a mammal, are described. In particular, 0157 proteins expressed specifically in vivo during human and cattle infection were identified. These proteins, mapped to the backbone, O-islands (OIs) and pO157. Because these-proteins are expressed during infection, and might help pathogens adapt to and counter hostile in vivo environments, those proteins identified in this study are useful as targets for drug and vaccine development. Also, such proteins are useful as markers of 0157 infection in stool specimens. Also described are methods of identifying immunogenic proteins.

Abstract: Methods are disclosed for rapidly and reliably differentiating between ischemic and hemorrhagic stroke events in a human patient. The methods include obtaining a biological sample, such as blood serum, and analyzing the sample or a derivative thereof by mass spectrometry to measure the amount of one or more targeted proteins differentially present and ischemic and hemorrhagic stroke patients. The analysis may include proteolytic digestion of the biological sample and selective reaction monitoring (SRM) tandem mass spectrometry of the digested sample to determine the amounts of surrogate peptides corresponding to the targeted proteins.

Abstract: Methods are described for monitoring the amounts of PTH variants in a biological sample by digesting the sample to produce surrogate peptides specific to the targeted PTH variants, and detecting and quantifying the surrogate peptides by selective reaction monitoring (SRM) mass spectrometry, using a set of precursor-to-product ion transitions optimized for sensitivity and selectivity. The PTH variants, or a portion thereof, may be concentrated in the sample by means of immunoaffinity capture or other suitable technique. The mass spectrometric method described herein enables the concurrent measurement of peptides representative of a plurality of targeted PTH variants in a single assay.

Abstract: The present invention relates to the identification and use of protein expression profiles with clinical relevance to osteoarthritis (OA). In particular, the invention provides the identity of marker proteins whose expression is correlated with OA and OA progression. Methods and kits are described for using these protein expression profiles in the study and/or diagnosis of OA, in the determination of the degree of advancement of OA, and in the selection and/or monitoring of treatment regimens. The invention also relates to the screening of drugs that modulate expression of these proteins or nucleic acid molecules encoding these proteins, in particular for the development of disease-modifying OA agents.

Abstract: The present invention relates to biomarkers in maternal serum samples and methods for predicting whether a fetus has Trisomy 21 during the first trimester of pregnancy based on the differential expression of a combination, or subcombination, of the same.

Abstract: A highly specific and sensitive technique for exploring cell physiology is disclosed. The method includes laser capture microdissection (LCM) for selecting small clusters of cells of interest from sections of tissue and matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) for characterizing simultaneously a broad variety of biological molecules present in the small cluster of cells.