Dh Technologies Development Pte. Ltd.

Eth Zurich

Eidgenossische Technische Hochschule Zurich

Biognosys Ag

Oliver Rinner

Rudolf Aebersold

Lukas Reiter

Stephen Alexander Tate

Ronald Francis Bonner

Pedro Jose Navarro Alvarez

Ludovic Gillet

Paola Picotti

Claudia Escher

Reto Ossola

Johan Malmstroem

Ruedi Aebersold

Systems and methods are disclosed for analyzing a sample using overlapping precursor isolation windows. A mass analyzer of a tandem mass spectrometer is instructed to select and fragment at least two overlapping precursor isolation windows across a precursor ion mass range of a sample using a processor. The tandem mass spectrometer includes a mass analyzer that allows overlapping precursor isolation windows across the mass range of the sample.

Data independent acquisition of product ion spectra and reference spectra library matching

A method of the analysis of compounds with mass spectrometry and to instruments, substances, and methods for polypeptide analysis, in particular in targeted proteomics applications and based on indexed retention times as peptide specific property. The method of chemical analysis comprises the steps of: a) providing a first sample comprising peptides; b) performing LC-MS and determining the empirical retention time values of the peptides; c) translating the empirical retention time values into the indexed retention time scale and associating a reference indexed retention time value; d) providing a second complex sample comprising peptides; e) performing LC-MS and determining the empirical retention time values; f) translating the empirical retention time values of the peptides into the indexed retention time scale by numerically adapting the transformation function; and g) determining the predicted empirical retention time value of the peptides by using the numerically adapted transformation function determined in step f).

Methods and systems for experimental set-up and data analysis in targeted proteomics applications

Systems and methods are disclosed for quantitating detectable compounds of a sample. Sample product ion spectra are received for each mass selection window for each time step. The received sample product ion spectra are searched for the presence of known compounds of interest with known product ion spectra by retrieving the known product ion spectra from a library, retrieving the sample product ion spectra corresponding to the precursor mass selection window expected to contain a precursor ion corresponding to the known product ion spectra, generating product ion traces in time for the sample product ion spectra for the known product ion spectra, calculating a score for the product ion traces and product ion spectra that represents how well known product ions and sample product ions match, and calculating a quantitative value for the known compound from the product ion traces when the score exceeds a threshold value.

Systems and methods are disclosed for identifying detectable compounds of a sample. Sample product ion spectra are received for each mass selection window of precursor mass selection windows for each time step. The received sample product ion spectra are searched for the presence of known compounds of interest with known product ion spectra by retrieving a known product ion spectrum from a library, retrieving the sample product ion spectra corresponding to the precursor mass selection window expected to contain a precursor ion corresponding to the known product ion spectrum, generating product ion traces in time for the retrieved sample product ion spectra, calculating a score for the product ion traces and the retrieved sample product ion spectra that represents how well the retrieved sample product ion spectra and the known product ion spectrum match, and confirming the identity of a precursor ion using the score.

Systems and methods are used to store an electronic record of all product ion spectra of all detectable compounds of a sample. A plurality of product ion scans are performed on a tandem mass spectrometer one or more times in a single sample analysis across a mass range using a plurality of mass selection windows. All sample product ion spectra of all detectable compounds for each mass selection window are produced. All sample product ion spectra for each mass selection window are received from the tandem mass spectrometer using a processor. All sample product ion spectra for each mass selection window are stored as an electronic record of all detectable compounds of the sample using the processor. The electronic record is used to characterize compounds known at the time the electronic record is stored or to characterize compounds that became known after the electronic record was stored.

The invention relates to a method for the determination of an MRM or SRM assay for a protein of interest, a peptide of interest, or a group of proteins/peptides of interest or a whole proteome. It essentially includes the following steps: (1) a list of proteins of interest is selected and for each member at least one or a list of candidate proteotypic peptides is derived (2) this at least one peptide is synthesized/generated essentially without subsequent purification; (3) this at least one unpurified peptide is analyzed by selected reaction monitoring (SRM) preferably coupled to liquid chromatography (LC-SRM) or analogous techniques; (4) validation and/or optimisation of the corresponding assay of the at least one peptide with determination of the SRM coordinates for a peptide/protein of interest and/or of a regulator of interest is achieved. A protein sample of interest is enzymatically digested and can then be analyzed in SRM mode or time-constrained SRM mode, using elution times to trigger acquisition of the set of selected SRM traces, thus drastically increasing the throughput. The analysis allows to detect and quantify the set of peptides/proteins of interest. The method additionally relates to a tagging strategy to achieve absolute quantification of the peptides/proteins of interest at low-budget and high-throughput.

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Zurich, Switzerland

Oliver Rinner