9 results about "Nucleic acid methylation" patented technology

The present disclosure provides methods and systems for screening or detecting colorectal cancer or subsequent colorectal disease progression, which can be applied to cell-free nucleic acids, such as cell-free DNA. The methods can train a machine learning model using detection of methylation signals within single sequencing reads in identified genomic regions as input features, and generate a classifier suitable for stratifying a population of individuals. The methods can include extracting DNA from a cell-free sample obtained from a subject, transforming the DNA for methylation sequencing, generating sequencing reads, and detecting colon proliferative cell disorder related signals in the sequencing information, and training a machine learning model to provide a discriminator capable of distinguishing between groups such as healthy, cancer, etc. in a population of subjects, or distinguishing between disease subtypes or stages. The methods can be used, for example, to predict, prognosticate, and / or monitor response to treatment, tumor burden, recurrence, or progression of colorectal cancer.

Methods and systems provided herein address current limitations of bisulfite-based methylation sequencing by improving the quality and accuracy of nucleic acid methylation sequencing and uses thereof for detection of disease. Methods that include minimally-destructive conversion methods for methylation sequencing as well as specialized UMI adapters provide for improved quality of sequencing libraries and sequencing information. Greater accuracy and more complete methylation-state information permits higher quality feature generation for use in machine learning models and classifier generation.

The present disclosure provides methods and systems for detecting colorectal cancer by nucleic acid methylation analysis. In particular, the present disclosure provides methods and systems for screening or detecting colorectal cancer or subsequent colorectal disease progression, which can be applied to cell-free nucleic acids, such as cell-free DNA. The method may train a machine learning model using detection of methylation signals within a single sequencing read in an identified genomic region as an input feature and generate a classifier suitable for layering a population of individuals. The method may include extracting DNA from a cell-free sample obtained from a subject, transforming the DNA for methylation sequencing, generating a sequencing read, and detecting a colonic proliferative cell disorder related signal in sequencing information, and training a machine learning model to provide a discriminator, the discriminator is capable of differentiating groups, such as health, cancer, or differentiating disease subtypes or stages, in a population of subjects. The methods are useful, for example, in predicting, prognosing, and / or monitoring response to treatment, tumor load, recurrence, or progression of colorectal cancer.

The present disclosure is concerned with modified proteins, methods, compositions, and kits for mapping of methylation status of nucleic acids, including 5-methylcytosine and 5-hydroxymethyl cytosine (5hmC). The proteins selectively act on certain modified cytosines of target nucleic acids and include one or more substitution mutations that enhance the selectivity of the proteins for certain modified cytosines, enhance the stability of the proteins, or enhance both selectivity and stability. Also provided are compositions and kits that include one or more of the proteins and methods for using one or more of the proteins.

Disclosed herein are compositions for preparing a target nucleic acid molecule comprising one or more 5-formylcytosine bases or adducts of 5-formylcytosine. Also disclosed herein are methods of efficiently synthesizing a nucleic acid molecule comprising one or more 5-formylcytosine bases from a target nucleic acid molecule comprising one or more 5-hydroxymethylcytosine bases. The disclosure also provides methods of detecting epigenetic modifications in a target nucleic acid molecule, such as those characterized by the methylation of cytosine at position 5 (e.g., 5-methylcytosine, 5-hydroxymethylcytosine).

This disclosure provides compositions for use in the preparation of target nucleic acid molecules, comprising one or more 5-formylcytosine bases or adducts of 5-formylcytosine. Also disclosed herein is a method for efficiently synthesizing nucleic acid molecules comprising one or more 5-formylcytosine bases from target nucleic acid molecules comprising one or more 5-hydroxymethylcytosine bases. This disclosure also provides a method for detecting epigenetic modifications in target nucleic acid molecules, such as epigenetic modifications characterized by methylation of cytosine at position 5 (e.g., 5-methylcytosine; 5-hydroxymethylcytosine).

A method for discriminating a cancer state is provided. A first dataset is obtained for a plurality of subjects having a first cancer state. Each subject has a plurality of nucleic acid methylation fragments with methylation patterns comprising CpG site methylation states. An autoencoder including an encoder and decoder is trained by evaluating the error in the autoencoder reconstruction of the methylation pattern and nucleic acid sequence of each nucleic acid methylation fragment in the first dataset. A second dataset is obtained for a plurality of subjects having a second cancer state. A plurality of features is identified by inputting the methylation pattern and nucleic acid sequence of each nucleic acid methylation fragment in the second dataset into the trained autoencoder and computing a score determined by the autoencoder reconstruction of the methylation pattern. The plurality of features is used to train a supervised model that discriminates a cancer state.

The present invention relates to a method for diagnosing, monitoring the effect of a treatment, monitoring the progression of a disease, or screening for a compound for treating a cerebral creatine deficiency syndrome, said method comprising the steps of measuring the level of nucleic acid methylation in a biological sample, and comparing the measured level with a control nucleic acid methylation level. The present invention also relates to folate and derivatives thereof for use in the treatment of a cerebral creatine deficiency syndrome.

The present application relates to a composition for determining the presence or absence of methylation of a nucleic acid and a method for determining the presence or absence of methylation of a nucleic acid.