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Methods and products for detecting in vitro the presence of damage on DNA or the presence of a biological response to damage on DNA at the molecular level. Molecular Combing or other nucleic acid stretching methods are employed together with compounds reacting with DNA, probes binding DNA, or nucleic acid monomers, especially labeled nucleic acid monomers.


Patent
Institute Pasteur Paris and Genomic Vision | Date: 2017-02-22

The present invention relates to a method of detection of the presence of at least one domain of interest on a macromolecule to test, wherein said method comprises the following steps:a) determining beforehand at least two target regions on the domain of interest, designing and obtaining corresponding labeled probes of each target region, named set of probe of the domain of interest, the position of these probes one compared to the others being chosen and forming the specific signature of said domain of interest on the macromolecule to test;b) after spreading of the macromolecule to test on which the probes obtained in step a) are bound, detection of the position one compared to the others of the probes bound on the linearized macromolecule, the detection of the signature of a domain of interest indicating the presence of said domain of interest on the macromolecule to test, and conversely the absence of detection of signature or part of signature of a domain of interest indicating the absence of said domain or part of said domain of interest on the macromolecule to test.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-10-2014 | Award Amount: 6.03M | Year: 2015

Cytogenetic diagnostic approaches provide information on the single-chromosome level but suffer from low resolution and throughput. In contrast, next generation sequencing (NGS) based diagnostics provides single base resolution and high throughput but suffer from short reads that prevent analysis of large genomic aberrations as well as being prone to PCR-amplification bias and erasure of epigenetic information. This proposal aims to bridge the gap between these domains by analyzing long individual DNA molecules without PCR-amplification via utilization of emerging optical DNA mapping technologies. We specifically address three types of challenges to current genomic based diagnostics: 1. Loss of relevant information such as DNA damage lesions, rare mutations or epigenetic markers following PCR amplification. 2. Limitations in resolving long-range variations in genomic layout and correlating them with single point mutations, preventing large scale screens. 3. Limitations imposed by the sample such as low sample amounts (micro biopsy, circulating tumor DNA) or inhomogeneous/highly variable samples (bacterial cultures). We will develop a robust toolbox for integrated genetic and epigenetic profiling of single DNA molecules that will include automated sample preparation of native unamplified DNA as well as the hardware and software platforms and analysis tools for readout, extraction and quantification of medically relevant genomic information. This technology will be used to develop a set of specific, proof of principle diagnostic assays based on optical barcoding of individual DNA molecules. These assays will address: -Bacterial infections and antibiotic resistance -Diagnosis/prognosis tools for hematological malignancies -Spinal Muscular Atrophy -Early diagnosis of colorectal and lung cancer. Ultimately our project will provide reagents, prototype DNA barcoding devices and data analysis software ready for large scale validation and early stage commercialization.


Methods for detecting the amplifications of sequences in the BRCA1 locus, which sequences have ends consisting of or are framed with sequence stretches present at least twice in the BRCA1 locus, and which amplification results in at least two or at least three, especially three, tandem copies of the amplified sequence; methods for determining a predisposition to diseases or disorders associated with these amplifications, including predisposition to ovarian cancer or breast cancer and methods for detecting amplifications with similar features in other loci and/or for predicting breakpoints of such amplifications.


Methods for detecting the amplifications of sequences in the BRCA1 locus, which sequences have ends consisting of or are framed with sequence stretches present at least twice in the BRCA1 locus, and which amplification results in at least two or at least three, especially three, tandem copies of the amplified sequence; methods for determining a predisposition to diseases or disorders associated with these amplifications, including predisposition to ovarian cancer or breast cancer and methods for detecting amplifications with similar features in other loci.


A method for detection, visualization and/or comparison of polynucleotide sequences of interest using specially designed sets of long and short probes that enhance resolution and simplify visualization and detection. Probe compositions useful for practicing this method and procedures for identifying useful probes and probe combinations. These methods are useful for the detection of genomic rearrangements, especially those associated with various diseases, disorders and conditions including cancer or for assessment of genomic rearrangements associated with therapy. The probe compositions may be used in kits for detection of genetic rearrangements or in companion diagnostic products or kits, such as kits for the diagnosis or assessment of predisposition to cancer such as colorectal cancer.


A method for detecting in vitro the presence of a genome of a DNA virus or a viral derived DNA in an infected eukaryotic cell, tissue or biological fluid using Molecular Combing or other nucleic acid stretching methods together with probes, especially nucleic acid probes, having a special design. A method for monitoring in vitro the effects of anti-viral treatment by following the presence of genomic viral or viral derived DNA polynucleotides in a virus-infected cell, tissue or biological fluid. Detection of an infectious form of a virus using Molecular Combing and DNA hybridization. A kit comprising probes used to carry out these methods and a composition comprising the probes.


Methods and products for detecting in vitro the presence of damage on DNA or the presence of a biological response to damage on DNA at the molecular level. Molecular Combing or other nucleic acid stretching methods are employed together with compounds reacting with DNA, probes binding DNA, or nucleic acid monomers, especially labeled nucleic acid monomers.


Methods and products for detecting in vitro the presence of damage on DNA or the presence of a biological response to damage on DNA at the molecular level. Molecular Combing or other nucleic acid stretching methods are employed together with compounds reacting with DNA, probes binding DNA, or nucleic acid monomers, especially labeled nucleic acid monomers.


Patent
Genomic Vision | Date: 2016-03-30

A method for easily, rapidly and accurately detecting rearrangements of HPV DNA in a host cell, tissue or biological fluid obtained from a subject or patient using Molecular Combing and/or DNA stretching in combination with specially designed probes for the infectious viral or pathogenic DNA sequence.

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