Abstract: In some embodiments, a mass spectrometry tag may comprise a linker region, a mass balance region, and a reporter region. The mass spectrometry tag may be configured to fragment in a mass spectrometer via an energy dependent process to produce multiple reporter molecules. For example, the reporter region of the tag may be configured to produce at least two reporter molecules via fragmentation. In some embodiments, one or more regions of the tag may comprise at least one heavy isotope. In some such embodiments, the ability to fragment into multiple reporter molecules as well as the placement and/or number of heavy isotope(s) allows the mass spectrometry tag to be distinguished from other similar mass spectrometry tags. In some such embodiments, the ability to distinguish between tags having the same or substantially similar total mass to charge ratio and reporter region mass may allow the system to have a greater multiplexing capacity than conventional systems.

Abstract: In some embodiments, a mass spectrometry tag may comprise a linker region, a mass balance region, and a reporter region. The mass spectrometry tag may be configured to fragment in a mass spectrometer via an energy dependent process to produce multiple reporter molecules. For example, the reporter region of the tag may be configured to produce at least two reporter molecules via fragmentation. In some embodiments, one or more regions of the tag may comprise at least one heavy isotope. In some such embodiments, the ability to fragment into multiple reporter molecules as well as the placement and/or number of heavy isotope(s) allows the mass spectrometry tag to be distinguished from other similar mass spectrometry tags. In some such embodiments, the ability to distinguish between tags having the same or substantially similar total mass to charge ratio and reporter region mass may allow the system to have a greater multiplexing capacity than conventional systems.

Abstract: The method for increasing contractility in patients with systolic heart failure involves screening for candidate small molecules which block the interaction between Rad and the plasma membrane and/or block the interaction between Rad and the CaV1.2/CaV?2 complex, or between Rad and CaV?2, in order to increase cardiac contractility. A method for preventing calcium overload and arrhythmias in heart disease involves preventing the dissociation of Rad and the CaV1.2/CaV?2 complex, or between Rad and CaV?2, during beta-adrenergic system activation. Additionally, a method of screening for drugs that block interaction between an RGK GTPase protein and a ?-subunit of the calcium channel is provided. A suitable technique, such as fluorescence resonance energy transfer (FRET), may be used to assess blocking of the interaction between the RGK GTPase protein and the ?-subunit of the calcium channel for the treatment of heart disease, pain, diabetes, skeletal muscle disorders and/or central nervous system (CNS) disorders.

Abstract: In some embodiments, a mass spectrometry tag may comprise a linker region, a mass balance region, and a reporter region. The mass spectrometry tag may be configured to fragment in a mass spectrometer via an energy dependent process to produce multiple reporter molecules. For example, the reporter region of the tag may be configured to produce at least two reporter molecules via fragmentation. In some embodiments, one or more regions of the tag may comprise at least one heavy isotope. In some such embodiments, the ability to fragment into multiple reporter molecules as well as the placement and/or number of heavy isotope(s) allows the mass spectrometry tag to be distinguished from other similar mass spectrometry tags. In some such embodiments, the ability to distinguish between tags having the same or substantially similar total mass to charge ratio and reporter region mass may allow the system to have a greater multiplexing capacity than conventional systems.

Abstract: In some embodiments, a mass spectrometry tag may comprise a linker region, a mass balance region, and a reporter region. The mass spectrometry tag may be configured to fragment in a mass spectrometer via an energy dependent process to produce multiple reporter molecules. For example, the reporter region of the tag may be configured to produce at least two reporter molecules via fragmentation. In some embodiments, one or more regions of the tag may comprise at least one heavy isotope. In some such embodiments, the ability to fragment into multiple reporter molecules as well as the placement and/or number of heavy isotope(s) allows the mass spectrometry tag to be distinguished from other similar mass spectrometry tags. In some such embodiments, the ability to distinguish between tags having the same or substantially similar total mass to charge ratio and reporter region mass may allow the system to have a greater multiplexing capacity than conventional systems.

Abstract: In some embodiments, a mass spectrometry tag may comprise a linker region, a mass balance region, and a reporter region. The mass spectrometry tag may be configured to fragment in a mass spectrometer via an energy dependent process to produce multiple reporter molecules. For example, the reporter region of the tag may be configured to produce at least two reporter molecules via fragmentation. In some embodiments, one or more regions of the tag may comprise at least one heavy isotope. In some such embodiments, the ability to fragment into multiple reporter molecules as well as the placement and/or number of heavy isotope(s) allows the mass spectrometry tag to be distinguished from other similar mass spectrometry tags. In some such embodiments, the ability to distinguish between tags having the same or substantially similar total mass to charge ratio and reporter region mass may allow the system to have a greater multiplexing capacity than conventional systems.

Abstract: The invention relates to methods of identifying compounds that modulate mTORC1 activity in a cell by modulating the activity of CASTOR1, as well as to the use of such identified compounds in the modulation of mTORC1 and the treatment of diseases and conditions characterized by aberrant mTORC1 activity.

Abstract: Described herein is a kit of materials prepared for assays that involve determining relative abundance and/or absolute abundance of various targeted peptides. The kit may comprise trigger versions of target peptides with masses offset from the respective target peptides by predetermined and known amounts. The trigger peptides may be present in amounts that may be readily detected via a mass spectrometry analysis. When mixed with samples that are analyzed, detection of the trigger peptides indicates where in the mass-spectrometer output the target peptide may be found. The kit may include a predetermined amount of synthetic versions of one or more of the target peptides. A measured relative abundance of this synthetic peptide relative to that of the target peptides yields an absolute quantitative value of the target peptide. Also disclosed is a method of preparing a plurality of samples to be submitted for mass spectrometer analysis in parallel.

Abstract: In some embodiments, a mass spectrometry tag may comprise a linker region, a mass balance region, and a reporter region. The mass spectrometry tag may be configured to fragment in a mass spectrometer via an energy dependent process to produce multiple reporter molecules. For example, the reporter region of the tag may be configured to produce at least two reporter molecules via fragmentation. In some embodiments, one or more regions of the tag may comprise at least one heavy isotope. In some such embodiments, the ability to fragment into multiple reporter molecules as well as the placement and/or number of heavy isotope(s) allows the mass spectrometry tag to be distinguished from other similar mass spectrometry tags. In some such embodiments, the ability to distinguish between tags having the same or substantially similar total mass to charge ratio and reporter region mass may allow the system to have a greater multiplexing capacity than conventional systems.

Abstract: Described herein is a kit of materials prepared for assays that involve determining relative abundance and/or absolute abundance of various targeted peptides. The kit may comprise trigger versions of target peptides with masses offset from the respective target peptides by predetermined and known amounts. The trigger peptides may be present in amounts that may be readily detected via a mass spectrometry analysis. When mixed with samples that are analyzed, detection of the trigger peptides indicates where in the mass-spectrometer output the target peptide may be found. The kit may include a predetermined amount of synthetic versions of one or more of the target peptides. A measured relative abundance of this synthetic peptide relative to that of the target peptides yields an absolute quantitative value of the target peptide. Also disclosed is a method of preparing a plurality of samples to be submitted for mass spectrometer analysis in parallel.

Abstract: A mass-spectrometry-based method and substrates are provided herein for large scale kinome activity profiling directly from crude lysates using 90 chemically synthesized peptide substrates with amino acid sequences derived from known phosphoproteins. Quantification of peptide phosphorylation rates was achieved via the use of stable isotope labeled synthetic peptides. A method and substrates for obtaining 90 simultaneous activity measurements in a single-reaction format were developed and validated. The kinome activity profiling strategy was successfully applied with lysates of: cells manipulated by combination of mitogen stimulation, pharmacological perturbation and siRNA-directed kinase knockdown; seven different breast cancer cell lines treated with gefitinib; and each of normal and cancerous tissue samples from renal cell carcinoma patients.

Abstract: The invention relates to methods of identifying compounds that modulate mTORC1 activity in a cell by modulating the activity of CASTOR1, as well as to the use of such identified compounds in the modulation of mTORC1 and the treatment of diseases and conditions characterized by aberrant mTORC1 activity.

Abstract: Embodiments are directed to a method, a computer readable medium encoded with instructions that, when executed, perform a method, and a system for performing mass spectrometry analysis. Molecules of different samples may be labeled with a chemical tag, allowing a multiplexed analysis of multiple samples. The labeled molecules may be fragmented, each fragmented molecule creating at least two separate ions. The relative abundance of each of the heavier ions, which may comprise the original molecule from the sample, may be measured. A relative abundance of the labeled molecules in each of the samples may be determined from the measured relative abundances of the heavier ions.

Abstract: Provided herein are compositions and methods for the treatment of HCMV infection in a subject.

Abstract: In some embodiments, a mass spectrometry tag may comprise a linker region, a mass balance region, and a reporter region. The mass spectrometry tag may be configured to fragment in a mass spectrometer via an energy dependent process to produce multiple reporter molecules. For example, the reporter region of the tag may be configured to produce at least two reporter molecules via fragmentation. In some embodiments, one or more regions of the tag may comprise at least one heavy isotope. In some such embodiments, the ability to fragment into multiple reporter molecules as well as the placement and/or number of heavy isotope(s) allows the mass spectrometry tag to be distinguished from other similar mass spectrometry tags. In some such embodiments, the ability to distinguish between tags having the same or substantially similar total mass to charge ratio and reporter region mass may allow the system to have a greater multiplexing capacity than conventional systems.

Abstract: A mass-spectrometry-based method and substrates are provided herein for large scale kinome activity profiling directly from crude lysates using 90 chemically synthesized peptide substrates with amino acid sequences derived from known phosphoproteins. Quantification of peptide phosphorylation rates was achieved via the use of stable isotope labeled synthetic peptides. Half of these peptides immediately or rapidly showed robust and site-specific phosphorylation after incubation with serum-starved HEK293 cell lysate. A method and substrates for obtaining 90 simultaneous activity measurements in a single-reaction format were developed and validated. Activating kinase pathways through insulin or EGF stimulation reproducibly altered the phosphorylation rates of peptides derived from known pathway protein substrates.

Abstract: Provided herein are compositions and methods for the treatment of HCMV infection in a subject.

Abstract: A method of performing a mass spectrometry analysis includes labeling each of a plurality of samples with a corresponding chemical tag; forming a first plurality of ions from molecules in the samples; selecting a subset of the first plurality of ions, the subset being selected by isolating ions of the first plurality of ions in a plurality of ranges of mass-to-charge; forming a second plurality of ions by fragmenting ions in the subset; and measuring information indicative of a quantity of each of the plurality of chemical tags present in each of the plurality of samples.

Abstract: A mass spectrometry technique for isolating a plurality of isolated ions from a plurality of injected ions using a dynamic isolation waveform to create at least one isolation notch. Isolating the plurality of isolated ions may include collecting at least a first target ion, but not a second target ion, using the at least one isolation notch for a first period of time; changing at least one property of the at least one isolation notch; and collecting at least the first target ion and the second target ion using the at least one isolation notch for a second period of time.

Abstract: Embodiments are directed to a method, a computer readable medium encoded with instructions that, when executed, perform a method, and a system for performing mass spectrometry analysis. Molecules of different samples may be labeled with a chemical tag, allowing a multiplexed analysis of multiple samples. The labeled molecules may be fragmented, each fragmented molecule creating at least two separate ions. The relative abundance of each of the heavier ions, which may comprise the original molecule from the sample, may be measured. A relative abundance of the labeled molecules in each of the samples may be determined from the measured relative abundances of the heavier ions.