247 results about "Epigenetic Profile" patented technology

We describe a method for interrogating the content and primary structure of DNA by microarray analyses and to provide comprehensive genetic screening and diagnostics prior to embryo transfer within an IVF setting. We will accomplish this by the following claims: 1) an optimized embryo grading system, 2) a less invasive embryo biopsy with reduced cellular contamination, 3) an optimized DNA amplification protocol for single cells, 4) identify aneuploidy and structural chromosome abnormalities using microarrays, 5) identifying sub-telomeric chromosome rearrangements, 6) a modified DNA fingerprinting protocol, 7) determine imprinting and epigenetic changes in developing embryos, 8) performing genome-wide scans to clarify / diagnose multi-factorial genetic disease and to determine genotype / haplotype patterns that may predict future disease, 9) determining single gene disorders with or without a known DNA mutation, 10) determining mtDNA mutations and / or the combination of mtDNA and genomic (nuclear) DNA aberrations that cause genetic disease.

The present invention relates to chemically modified genomic sequences of genes associated with the immune system, to oligonucleotides and / or PNA-oligomers directed against the sequence, for the detection of the methylation status of genes, associated with the immune system as well as to a method for ascertaining genetic and / or epigentic parametres of genes, associated with the immune system.

The invention relates to methods and products for enhancing and improving recovery of lost memories. In particular the methods are accomplished through the increase of histone acetylation.

The present invention provides RNA-guided endonucleases, which are engineered for expression in eukaryotic cells or embryos, and methods of using the RNA-guided endonuclease for targeted genome modification in eukaryotic cells or embryos. Also provided are fusion proteins, wherein each fusion protein comprises a CRISPR / Cas-like protein or fragment thereof and an effector domain. The effector domain can be a cleavage domain, an epigenetic modification domain, a transcriptional activation domain, or a transcriptional repressor domain. Also provided are methods for using the fusion proteins to modify a chromosomal sequence or regulate expression of a chromosomal sequence.

The present invention provides, inter alia, a method for generating a genome-wide epigenomic map, comprising a correlation between methylation variable CpG positions (MVP) and genomic DNA sample types. MVP are those CpG positions that show a variable quantitative level of methylation between sample types. Particular genomic regions of interest (ROI) provide preferred marker sequences that comprise multiple, and preferably proximate MVP, and that have novel utility for distinguishing sample types. The epigenic maps have broad utility, for example, in identifying sample types, or for distinguishing between and among sample types. In a preferred embodiment the epigenomic map is based on methylation variable regions (MVP) within the major histocompatibility complex (MHC), and has utility, for example, in identifying the cell or tissue source of a genomic DNA sample, or for distinguishing one or more particular cell or tissue types among other cell or tissue types. Analysis of epigenetic characteristics of one, or of a set of nucleic acid sequences, in the context of an inventive epigenomic map, allows for the determination of an origin of the nucleic acids.

The present invention provides methods and materials related to the detection of colorectal neoplasm-specific markers (e.g., markers associated with colorectal cancer, markers associated with adenoma) in or associated with a subject's stool sample. In particular, the present invention provides methods and materials for identifying mammals (e.g., humans) having a colorectal neoplasm by detecting the presence and level of indicators of colorectal neoplasia such as, for example, long DNA (e.g., quantified by Alu PCR) and the presence and level of tumor-associated gene alterations (e.g., mutations in KRAS, APC, melanoma antigen gene, p53, BRAF, BAT26, PIK3CA) or epigenetic alterations (e.g., DNA methylation) (e.g., CpG methylation) (e.g., CpG methylation in coding or regulatory regions of bmp-3, bmp-4, SFRP2, vimentin, septin9, ALX4, EYA4, TFPI2, NDRG4, FOXE1) in DNA from a stool sample obtained from the mammal.

Methods are provided for the identification of compounds that selectively modulate epigenetic changes in gene expression. Compounds, compositions, kits or assays devices, and methods are provided for modulating the expression, endogenous levels or the function of small non-coding RNAs cognate to or transcribed by heterochromatic regions subject to epigenetic regulation (i.e., promoters, enhancers, centromeres, telomeres, origins of DNA replication, imprinted loci, or loci marked by dosage-compensation), and for modulating the formation or function of heterochromatin in cells, tissues or animals.

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.

Cancer therapies that combine epigenetic modulating agent(s) with immune modulating agent(s), which were remarkably identified to provide an improved treatment regimen over single agent therapy, are disclosed. In particular embodiments, the invention provides for improved treatment of NSCLC in patients via administration of exemplary immune modulating agents anti-PD-1 antibody or anti-PD-L1 antibody, which were observed to show enhanced activity in combination with the exemplary epigenetic modulating agent 5-deoxyazacytidine. Further, expression markers of responsive neoplastic cells are also disclosed.

Engineered transcriptional activator-like effectors (TALEs) are versatile tools for genome manipulation with applications in research and clinical contexts. One current drawback of TALEs is that the 5′ nucleotide of the target is specific for thymine (T). TALE domains with alternative 5′ nucleotide specificities could expand the scope of DNA target sequences that can be bound by TALEs. Another drawback of TALEs is their tendency to bind and cleave off-target sequence, which hampers their clinical application and renders applications requiring high-fidelity binding unfeasible. This disclosure provides methods and strategies for the continuous evolution of proteins comprising DNA-binding domains, e.g., TALE domains. In some aspects, this disclosure provides methods and strategies for evolving such proteins under positive selection for a desired DNA-binding activity and / or under negative selection against one or more undesired (e.g., off-target) DNA-binding activities. Some aspects of this disclosure provide engineered TALE domains and TALEs comprising such engineered domains, e.g., TALE nucleases (TALENs), TALE transcriptional activators, TALE transcriptional repressors, and TALE epigenetic modification enzymes, with altered 5′ nucleotide specificities of target sequences. Engineered TALEs that target ATM with greater specificity are also provided.

A method of detecting a predisposition to, or the incidence of colorectal cancer in a faecal sample comprises, in a first step (a), detecting the presence of blood in the faecal sample, wherein detection of the presence of blood is indicative of a predisposition to, or the incidence of colorectal cancer. The method additionally comprises, in second step (b), detecting an epi-genetic modification in the DNA contained within the faecal sample, wherein detection of the epigenetic modification is indicative of a predisposition to, or the incidence of colorectal cancer. Based upon a positive result obtained in either (a) or (b) or in both (a) and (b) a predisposition to, or the incidence of colorectal cancer is detected. Related methods and kits involve detecting an epigenetic modification in a number of specific genes.

Engineered transcriptional activator-like effectors (TALEs) are versatile tools for genome manipulation with applications in research and clinical contexts. One current drawback of TALEs is that the 5′ nucleotide of the target is specific for thymine (T). TALE domains with alternative 5′ nucleotide specificities could expand the scope of DNA target sequences that can be bound by TALEs. This disclosure provides methods and strategies for the continuous evolution of proteins comprising DNA-binding domains, e.g., TALE domains. In some aspects, this disclosure provides methods and strategies for evolving such proteins under positive selection for a desired DNA-binding activity and / or under negative selection against one or more undesired (e.g., off-target) DNA-binding activities. Some aspects of this disclosure provide engineered TALE domains and TALEs comprising such engineered domains, e.g., TALE nucleases (TALENs), TALE transcriptional activators, TALE transcriptional repressors, and TALE epigenetic modification enzymes, with altered 5′ nucleotide specificities of target sequences. Engineered TALEs that target ATM with greater specificity are also provided.

The present invention relates to the field of cancer. More specifically, the present invention provides methods and compositions useful for assessing prostate cancer. In a specific embodiment, present inventors have developed and applied a new technology and associated computation methods enabling simultaneous genome-scale analysis of genetic (copy number) and epigenetic (total methylation (TM) and allele-specific methylation (ASM) alternation, This method, called MBD-SNP, features affinity enrichment or methylated genomic DNA fragments using a methyl-binding domain polypeptide.

A method of detecting a predisposition to, or the incidence of, colorectal cancer in a fecal sample comprises, in a first step (a), detecting the presence of blood in the fecal sample, wherein detection of the presence of blood is indicative of a predisposition to, or the incidence of, colorectal cancer. The method additionally comprises, in second step (b), detecting an epigenetic modification in the DNA contained within the fecal sample, wherein detection of the epigenetic modification is indicative of a predisposition to, or the incidence of, colorectal cancer. Based upon a positive result obtained in either (a) or (b) or in both (a) and (b) a predisposition to, or the incidence of, colorectal cancer is detected. Related methods and kits involve detecting an epigenetic modification in a number of specific genes.

Methods are provided for treating patients with epigenetic diseases, especially those associated with aberrant DNA methylation such as hematological disorders and cancer. By administering a DNA methylation inhibitor to the patients following unique dosing regimens, the disease can be efficaciously treated with reduced toxic side effects.

The present invention provides methods and materials related to the detection of colorectal neoplasia (CRN) associated with inflammatory bowel disease (IBD). The present invention provides markers specific for colorectal neoplasia associated with inflammatory bowel disease in or associated with a subject's stool sample. In particular, the present invention provides methods and materials for identifying mammals (e.g., humans) having colorectal neoplasia associated with inflammatory bowel disease by detecting the presence and level of indicators of colorectal neoplasia such as, for example, epigenetic alterations (e.g., DNA methylation) (e.g., CpG methylation) (e.g., CpG methylation in coding or regulatory regions of BMP3, NDRG4, vimentin, EYA4) in DNA from a stool sample obtained from the mammal.

Engineered transcriptional activator-like effectors (TALEs) are versatile tools for genome manipulation with applications in research and clinical contexts. One current drawback of TALEs is that the 5′ nucleotide of the target is specific for thymine (T). TALE domains with alternative 5′ nucleotide specificities could expand the scope of DNA target sequences that can be bound by TALEs. This disclosure provides methods and strategies for the continuous evolution of proteins comprising DNA-binding domains, e.g., TALE domains. In some aspects, this disclosure provides methods and strategies for evolving such proteins under positive selection for a desired DNA-binding activity and / or under negative selection against one or more undesired (e.g., off-target) DNA-binding activities. Some aspects of this disclosure provide engineered TALE domains and TALEs comprising such engineered domains, e.g., TALE nucleases (TALENs), TALE transcriptional activators, TALE transcriptional repressors, and TALE epigenetic modification enzymes, with altered 5′ nucleotide specificities of target sequences. Engineered TALEs that target ATM with greater specificity are also provided.

The present invention concerns the chemically modified genomic sequences of genes associated with angiogenesis, oligonucleotides and / or PNA oligomers directed against the sequence for the detection of the cytosine methylation state of genes associated with angiogenesis as well as a method for determining genetic and / or epigenetic parameters of genes associated with angiogenesis.

The present invention relates to chemically modified genomic sequences, to oligonucleotides and / or PNA-oligomers for detecting the cytosine methylation state of genomic DNA, as well as to a method for ascertaining genetic and / or epigenetic parameters of genes for use in characterisation, classification, differentiation, diagnosis and therapy of prostate lesions.

The invention features methods of diagnosing cancer in a mammal (e.g., a human) by detecting a biomarker selected from a satellite II ribonucleic acid (RNA) molecule, a cancer-associated polycomb group (CAP) body, a cancer-associated satellite transcript (CAST) body, and UbH2A. Also featured is a method for identifying an agent for treating cancer in a mammal by contacting a cancer cell having a biomarker selected from a CAP body, a CAST body, and a satellite II RNA molecule with a test agent and determining whether the test agent reduces the level of the biomarker in the cancer cell. Other inventions featured are a method for determining whether a chemotherapeutic agent increases epigenetic imbalance of a cell and a method for detecting epigenetic imbalance by determining a copy number of a satellite II DNA locus at chromosome 1q12 in a cell.

The present disclosure provides genetically engineered cell lines comprising chromosomally integrated synthetic sequences having predetermined epigenetic modifications, wherein a predetermined epigenetic modification is correlated with a known diagnosis, prognosis or level of sensitivity to a disease treatment. Also provided are kits comprising said epigenetically modified synthetic nucleic acids or cells comprising said epigenetically modified synthetic nucleic acids that can be used as reference standards for predicting responsiveness to therapeutic treatments, diagnosing diseases, or predicting disease prognosis.

The present invention relates to the chemically modified genomic sequences of genes associated with cell cycle, to oligonucleotides and / or PNA-oligomers for detecting the cytosine methylation state of genes associated with cell cycle which are directed against the sequence, as well as to a method for ascertaining genetic and / or epigenetic parameters of genes associated with cell cycle.