US Patent 7,400,980. Methods of detecting DNA variation in sequence data
Inventors: Chan Sheng Liu, Fei Gao
Describes a method for detecting DNA variation. First, trace data of a sample DNA sequence is aligned to trace data of a reference DNA sequence. After that, the trace data of the bases of both the reference DNA sequence and the aligned sample DNA sequence for a particular frame number are put into a non-linear mathematical function of an anti-correlation calculation scheme for all the frame numbers. Minimal values are produced at a particular frame number when no variation is present. Values above the minimal values indicate a variation as compared to the reference DNA sequence.
US Patent 7,399,852. Kits and reaction mixtures containing modified probe molecules
Inventors: Michael Becker, Mehrdad Majlessi, Steven Brentano
The invention concerns oligonucleotides containing one or more modified nucleotides that increase the binding affinity of the oligonucleotides to target nucleic acids with a complementary sequence. The modified oligonucleotides hybridize to the target sequence at a faster rate than unmodified oligonucleotides with an identical sequence. They include oligonucleotides containing at least one 2'-O-methylribofuranosyl moiety joined to a nitrogenous base. Oligonucleotides can be modified to preferentially bind RNA targets. The invention also concerns methods of using the modified oligonucleotides and kits containing them.
US Patent 7,399,846. Libraries of oligomers labeled with different tags
Inventors: Ed Southern, Mikhail Shchepinov, John Housby, Alan Hamilton, John Elder
Assignee: Oxford Gene Technology IP
Describes a method of making a set of labelled compounds that uses a preferably particulate support. It comprises dividing the support into lots, performing a different chemical reaction on each lot of the support, e.g. to couple a chemical moiety to it, tagging a fraction of each lot with a different label, and combining the lots. The steps are repeated several times, preferably to build up oligomers carrying labels that identify the nature and position of a monomer unit, and which are releasable from the support. Preferred labels, which can be released by cleavage to provide charged groups for analysis by mass spectrometry, are groups of the trityl (trimethylphenyl) family. The patent also claims libraries of the labels and their use in assays and nucleic acid analysis methods.
US Patent 7,399,844. Method and reagents for analyzing the nucleotide sequence of nucleic acids
Inventors: Jeffrey Sampson, Joel Myerson, Anna Tsalenko, Nicholas Sampas, Peter Webb, Zohar Yakhini
Assignee: Agilent Technologies
Discloses methods and reagents for more sensitive, more accurate and higher throughput analyses of target nucleic acid sequences. These may be generically applied to any target nucleic acid sequence and do not require a priori information about the presence, location, or identity of mutations in the target. The reagents of the invention are mixtures of oligonucleotide precursors with a high level of coverage and mass number complexity. They also have tags that can be analyzed by mass spectrometry which are covalently linked to the precursors through cleavable bonds. The patent also describes a method for analyzing a target nucleic acid sequence using the mixtures of oligonucleotide precursors, and chemical or enzymatic assays to alter the mass of the oligonucleotide precursors prior to mass spectral analysis. The enzymatic assay may be a polymerase extension assay or a ligation-based assay. Kits for carrying out the methods of the invention are also disclosed.
US Patent 7,393,665. Methods and compositions for tagging and identifying polynucleotides
Inventor: Sydney Brenner
Assignee: Population Genetics Technologies
Provides methods and compositions for attaching oligonucleotide tags to polynucleotides for carrying out analytical assays in parallel and for decoding the oligonucleotide tags of polynucleotides selected in such assays. Words, or subunits, of oligonucleotide tags index submixtures in successively more complex sets of submixtures that a polynucleotide goes through while successive words are added to a growing tag. By identifying each word of an oligonucleotide tag, a series of submixtures is identified, including the first submixture that contains only a single polynucleotide, thereby providing the identity of the selected polynucleotide. The analysis of the words of an oligonucleotide tag can be carried out in parallel, e.g. by specific hybridization of the oligonucleotide tag to its tag complement on an addressable array; or such analysis can be carried out serially, for example by successive specific hybridizations of labeled word complements.
US Patent 7,393,640. Terminal-phosphate-labeled nucleotides with new linkers
Inventors: Shiv Kumar, Mark McDougall, Anup Sood, John Nelson, Carl Fuller, John Macklin, Paul Mitsis
Assignee: GE Healthcare Bio-Sciences
Describes methods of using terminal-phosphate-labeled nucleotides in the presence of a manganese salt to enhance their substrate properties towards various enzymes. It includes methods of detecting a nucleic acid in a sample, based on the use of terminal-phosphate-labeled nucleotides as substrates for nucleic acid polymerases, in the presence of a manganese salt. Further provided are manganese complexes of terminal-phosphate-labeled nucleotides as well as terminal-phosphate-labeled nucleotides with new linkers with enhanced substrate properties.