Sequenom, Inc.

Genetrace Systems, Inc.

Sri International

Thermo Finnigan LLC

Surromed, Inc.

Ppd Biomarker Discovery Sciences, LLC

Biogen Idec Ma Inc.

Caprion Proteomics Usa, LLC

Christopher Hank Becker

Joseph Albert Monforte

Thomas Andrew Shaler

Daniel J Pollart

Yuping Tan

Hua Lin

Scott M Norton

Curtis A Hastings

Jia Li

John M Butler

Sidney E Buttrill

Aaron B Kantor

Joanna M Hunter

James R Ladine

Steven E Young

Jun Deng

Markus Anderle

Keith T Gillen

Chia-Hui Paul Shieh

Sushmita Mimi Roy

Weixun Wang

Haihong Zhou

Praveen Kumar

Susan Goelz

Releasable tag reagents for use in the detection and analysis of target molecules, particular in mass spectrometric analyzes are provided. Also provided are methods of detection that employ releasable tag reagents.

Releasable nonvolatile mass-label molecules

Releasable tag reagents for use in the detection and analysis of target molecules, particular in mass spectrometric analyses are provided. Also provided are methods of detection that employ releasable tag reagents.

Methods and reagents for obtaining simplified mixtures of peptides from a sample containing a number of peptides are disclosed. The simplified sample can be easier to analyze than the original peptide sample yet it is representative of all or nearly all of the proteins present in the mixed protein sample from which the original and more complex peptide sample was derived. The methods entail the use of tagging moieties that include an amino-acid-specific reactive group (R). The tagging moieties 'tag' peptides or proteins at specific amino acids (e.g., by reacting with an amino acid to form a covalent bond), ultimately allowing the isolation of peptides that contain those specific amino acids. Other methods entail the used of a reactive moiety (R) that comprises a reagent that selectively interacts with selected proteins, either covalently or noncovalently. For example, Rcan be a natural ligand for a receptor that is to be tagged or a protein that interacts with a second protein that is to be tagged. It can be an enzymatic substrate or other element of molecular recognition such as an antibody, ATP, GTP, NAD, NADP, NADH, NADPH, ubiquitin, or structural analogs thereof.

Methods and kits useful for the simplification of complex peptide mixtures

Relative quantitative information about components of chemical or biological samples can be obtained from mass spectra by normalizing the spectra to yield peak intensity values that accurately reflect concentrations of the responsible species. A normalization factor is computed from peak intensities of those inherent components whose concentration remains constant across a series of samples. Relative concentrations of a component occurring in different samples can be estimated from the normalized peak intensities. Unlike conventional methods, internal standards or additional reagents are not required. The methods are particularly useful for differential phenotyping in proteomics and metabolomics research, in which molecules varying in concentration across samples are identified. These identified species may serve as biological markers for disease or response to therapy.

Mass spectrometric quantification of chemical mixture components

The present invention provides modified oligonucleotide primers designed to incorporate a cleavable moiety so that a 3' portion of the primer (linked to an extension product) can be released from an upstream 5&#x2032; portion of the primer. Upon selective cleavage of the cleavable site, primer extension products that contain about five or fewer base pairs of the primer sequence are released, to provide more useful sizing and sequence information per fragment than extension products containing the entire primer.

Primers useful for sizing nucleic acids

The present invention is related to the fields of genetic mapping and genetic identity detection, including forensic identification and paternity testing. This invention is more specifically directed to the use of mass spectrometry to detect length variation in DNA nucleotide sequence repeats (including variants of common alleles), such as microsatellites and short tandem repeats, and to DNA sequences provided as primers for the analysis of DNA tandem nucleotide repeat polymorphisms at specific loci on specific chromosomes.

DNA typing by mass spectrometry with polymorphic DNA repeat markers

Using nonvolatile, releasable, mass-labels, the present invention provides for the synthesis and use of mass-labeled compounds to specifically interact with biomolecular targets. Following binding of the mass-labeled compounds to the target molecule, the unique mass-label can be analyzed using mass spectrometry to identify and characterize the target molecule. In one embodiment of the invention, a mass-labeled oligonucleotide probe is used to identify a specific gene sequence. A myriad of mass-labeled compounds may be produced for use in a wide variety of interactions such as oligonucleotide-oligonucleotide hybridization, polynucleotide-polynucleotide interactions, enzyme-substrate or substrate analog/intermediate interactions, polypeptide-nucleic acid interactions, protein-ligand interactions, receptor-ligand interactions, polypeptide-metal interactions, nucleic acid-metal interactions or antigen-antibody interactions. Also contemplated are combinatorial processes for creating large libraries of compounds permitting rapid screening for a wide variety of targets.

Releasable nonvolatile mass label molecules

This invention relates to methods for screening nucleic acids for polymorphisms by analyzing amplified target nucleic acids using mass spectrometric techniques and to procedures for improving mass resolution and mass accuracy of these methods of detecting polymorphisms.

Methods of preparing nucleic acids for mass spectrometric analysis

This invention relates to methods for screening nucleic acids for mutations by analyzing nonrandomly fragmented nucleic acids using mass spectrometric techniques and to procedures for improving mass resolution and mass accuracy of these methods of detecting mutations.

Methods of screening nucleic acids using volatile salts in mass spectrometry

A sample preparation method is disclosed for volatilization and mass spectrometric analysis of nonvolatile high molecular weight molecules. Photoabsorbing molecules having significant sublimation rates at room temperature under vacuum, and preferably containing hydroxy functionalities, are disclosed for use as matrices in matrix-assisted laser desorption/ionization mass spectrometry. The samples are typically cooled in the mass spectrometer to temperatures significantly below room temperature.

Volatile matrices for matrix-assisted laser desorption/ionization mass spectrometry

Volatile matrices for matrix-assisted laser desorption/ionization mass

This invention relates to methods for screening nucleic acids for mutations by analyzing nonrandomly fragmented nucleic acids using mass spectrometric techniques and to procedures for improving mass resolution and mass accuracy of these methods of detecting

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Palo Alto, CA, United States of America

Christopher Hank Becker