Abstract: The invention concerns a method for the identification of cytosine methylation patterns in genomic DNA samples, wherein a) a genomic DNA sample is chemically treated such that cytosine and 5-methylcytosine react differently and a different base pairing behavior of the two products results in the duplex; b) parts of the thus-treated DNA sample are enzymatically amplified; c) the amplified parts of the thus-treated DNA sample bind to a surface; d) a set of probes of different nucleobase sequences, each of which contains the dinucleotide sequence 5?-CpG-3? at least once, is hybridized to the immobilized DNA sample; e) the non-hybridized probes are separated; f) the hybridized probes are analyzed in a mass spectrometer, wherein the position of the probes on the sample holder permits a classification of the hybridizing DNA sample; g) Assignment of the peak pattern obtained from the mass spectra to the methylation pattern and comparison of the new data with a database.

Abstract: Described is a method for methylation detection in a DNA sample. An isolated genomic DNA sample is treated in a manner capable of distinguishing methylated from unmethylated cytosine bases. The pretreated DNA is amplified using at least one oligonucleotide primer, a polymerase and a set of nucleotides of which at least one is labeled with a first type of label. A sequence-specific oligonucleotide probe, marked with a second type of label, hybridizes to the amplification product and a FRET reaction occurs if a labeled oligonucleotide is present in close proximity in the amplification product. The method determines the level of methylation of a sample by measuring the extent of fluorescence resonance energy transfer (FRET) between the donor and acceptor fluorophore.

Abstract: The present invention relates to methods for detecting free floating nucleic acids, as present in not cellular bound nucleic acids in bodily fluids like plasma or serum fractions of human or animal blood or in any other tissue samples derived from the human or animal body in order to diagnose a cell proliferative disease. Specifically the invention relates to the detection of increased levels of nucleic acids in bodily fluids. Furthermore the invention allows to determine the source of the enriched DNA by measuring the ratio of DNA originating from a certain organ versus total DNA from other organs in a given bodily fluid sample by specifying the DNA's methylation pattern. This can be done with or without increasing the DNA concentration of a given biological sample. In a preferred embodiment a further analysis of this methylation pattern allows for the detection of the presence of tumourous or otherwise proliferative disease in said organ.

Abstract: An oligomer array with PNA (peptide nucleic acid) and/or DNA oligomers on a surface is described, which comprises oligomers of between 6 and 20 monomers or nucleobases each, whereby each of these contains at least one sequence of the general formula DDCGDD or of the general formula DDTGDD or of the general formula HHCGHH or of the general formula HHCAHH, wherein H indicates one of the bases: adenine (A), cytosine (C), or thymine (T) and D represents one of the bases: adenine (A), guanine (G) or thymine (T), and wherein the site of the oligomers on the surface is correlated with the sequence of the oligomers. The oligomer arrays according to the invention are used for the detection of cytosine methylations in genomic DNA.

Abstract: The present invention describes a method for the analysis of methylation patterns comprising the following steps: a) isolation of genomic nucleic acids from a biological sample, b) amplification of one or more target nucleic acids of said genomic nucleic acids in a manner whereby the methylation patterns of said genomic nucleic acids are maintained in the amplificate nucleic acid, c) performing mass spectrometry on said amplified nucleic acid or fragments thereof to obtain mass spectra; d) evaluating the obtained mass spectra and e) determining the methylation pattern and/or methylation status of the sample. The disclosed invention provides novel methods for the analysis of cytosine methylation patterns within genomic DNA samples. Said method comprises a methylation retaining enzymatic amplification of a test nucleic acid sample, followed by mass spectrometric analysis of the amplificate nucleic acids.

Abstract: The invention outlines a method for the methylation pattern retaining amplification of nucleic acid molecules. Furthermore the invention describes several devices for use in the methylation pattern retaining amplification of nucleic acid molecules.

Abstract: A sample holder is described, which is loaded with metal or glass slides. This arrangement serves for the analysis of DNA arrays in the MALDI-TOF mass spectrometer.

Abstract: Systems, methods and computer program products for guiding selection of a therapeutic treatment regimen or a preventive therapeutic treatment regimen are disclosed. The method comprises (A) providing to a computing device comprising a first knowledge base comprising information about a plurality of different methylation statuses at selected sites of the DNA in cells with a known disease or medical condition and/or healthy cells, a second knowledge base comprising a plurality of expert rules for evaluating and selecting a type of disease or medical condition based on the methylation status at selected sites of the DNA of a patient, (B) generating in said computing device a ranked listing of diseases or medical conditions based on the information about the methylation status at selected sites of the DNA of the patient, the first knowledge base and the second knowledge base.

Abstract: A device and a method for the photolithographic exposure of biological substances is described, which comprises at least one light source, a bundle of optical fibers and a control unit, whereby each of the optical fibers can be controlled by light independently from one another and/or light can be coupled to each fiber independently. The device is particularly suitable for the exposure of DNA, PNA or peptide chips.

Abstract: The present invention provides for molecular GSTP1 markers that have novel utility for the analysis of methylation patterns within the promoter region and exons 1 and 2 of the GSTP1 gene, and are further useful in methods to effectively distinguish among benign hyperplasia of the prostate and different grades of prostate cancer. Additionally, the subject molecular GSTP1 markers have novel utility for the precise localization of the zone of origin to provide sensitive, accurate and non-invasive methods for the diagnosis and/or prognosis of prostate cell proliferative disorders. The present invention has novel utility for the detection and differentiation of a cell proliferative disorder of the peripheral zone of the prostate.

Abstract: A method for selecting epigenetic features includes receiving an epigenetic feature data set for a plurality of epigenetic features of interest. The epigenetic feature data set is grouped in disjunct classes of interest. Epigenetic features of interest and/or combinations of epigenetic features of interest are selected that are relevant for epigenetically-based prediction based on corresponding epigenetic feature data. A new set of epigenetic features of interest is defined based on the relevant epigenetic features of interest and/or combinations of epigenetic features of interest.

Abstract: The present invention provides a novel method for the systematic identification of differentially methylated CpG dinucleotides positions within genomic DNA sequences for use as reliable diagnostic, prognostic and/or staging markers. Particular embodiments comprise genome-wide identification of differentially methylated CpG dinucleotide sequences, further identification of neighboring differentially methylated CpG dinucleotide sequences, and confirmation of the diagnostic utility of selected differentially methylated CpG dinucleotide among a larger set of diseased and normal biological samples. The method, and kits for implementation thereof, are useful in applied assays for the diagnosis, prognosis and/or staging of conditions characterized by differential methylation.

Abstract: The present invention provides methods for identification of methylated, and/or potentially methylatable CpG dinucleotides in genomic DNA sequences, and methods for isolating genomic DNA sequences comprising methylated CpG dinucleotide sequences. The present invention further provides methods for comparison of the methylation status of specific CpG dinucleotides, and patterns thereof between normal and diseased genomic DNA sequences, along with methods for determining all potentially methylatable CpG dinucleotides in a genomic DNA sample. Specifically, the present invention discloses a novel use of 5-methylcytosine DNA glycosylase (5-MCDG) in combination with art-recognized DNA base excision repair (BER) enzymes, and in particular embodiments, in combination with DNA methyltransferase to specifically label methylated CpG dinucleotide sequences in genomic DNA sequences.

Abstract: This invention concerns systems for collecting and storing epigenetic and phenotypic information about samples in order to measure and analyse tissue samples and/or cell lines, where the epigenetic parameter is DNA methylation and the phenotypic parameters describe an individual. The method includes parameters such as the diagnosis of diseases and/or drug resistance, wherein the correlation of the epigenetic with the phenotypic parameters is done substantially without human intervention.

Abstract: Method for characterizing, classifying and differentiating tissues and cell types, for predicting the behavior of tissues and groups of cells, and for identifying genes with changed expression. The method involves obtaining genomic DNA from a tissue sample, the genomic DNA subsequently being subjected to shearing, cleaved by means of a restriction endonuclease or not treated by either one of these methods. The base cytosine, but not 5-methylcytosine, from the thus-obtained genomic DNA is then converted into uracil by treatment with a bisulfite solution. Fractions of the thus-treated genomic DNA are then amplified using either very short or degenerated oligonucleotides or oligonuclcotides which are complementary to adaptor oligonucleotides that have been ligated to the ends of the cleaved DNA.