The present invention relates to methods for RNA-directed cleaving of a nucleic acid molecule selected from dsDNA, ssDNA, and RNA based on a complex comprising a Cas? nuclease and at least one pre-selected guide RNA designed for binding to at least one target RNA. Further provided is the complex of the present invention bound to a target RNA molecule, as well as respective systems for cleaving of a nucleic acid molecule, and diagnostic and therapeutic uses thereof.

The present invention relates to methods for isolating nucleic acids present in a sample, in particular cell-free DNA (cfDNA) from a blood sample and polymers, substrates and kits for the method. Polymers with characteristics suitable to bind such nucleic acids are provided.

The disclosure relates to the field of biomarkers to diagnose a disease, more particularly to the field of biomarkers to diagnose cancer, and most particularly to colorectal cancer. Specifically, these biomarkers are expressed in monocytes of a subject, particularly circulating monocytes, as can be isolated from peripheral blood. The markers are particularly useful for early detection of cancer.

An automated method for performing an assay of the present disclosure can be performed in a microfluidic device that is a lateral flow device having numerous features to ensure correct operation of the device under gravity, such as vent pockets for enabling the flow of sample fluid from one chamber to the next when the vent pocket is unsealed. Each chamber can have a reagent recess proximal to an inlet end of the chamber. A reagent pellet formed in a reagent recess can be effectively mixed with a sample as the sample flows into the chamber. A flexible circuit with patterned metallic electrical components disposed on a heat stable material can be in direct contact with fluid in the chambers and has resistive heating elements aligned with, for example, a chamber for performing an amplification reaction. A lateral flow detection chamber can include a capillary pool proximal to a sample receiving end of a lateral flow strip, providing effective mixing and dispersion of a sample with detection particles, as well as enhancing, uniformity of particle migration on the detection strip. The microfluidic device can be configured to be hermetically sealed, thereby preventing contamination of a testing environment.

This invention relates to methods and compositions for assessing risk by measuring total and specific cell-free nucleic acids (such as DNA) in a subject. The methods and compositions provided herein can be used to determine risk of a condition, such as transplant rejection.

Systems, methods, and apparatuses for generating and using machine learning models using genetic data. A set of input features for training the machine learning model can be identified and used to train the model based on training samples, e.g., for which one or more labels are known. As examples, the input features can include aligned variables (e.g., derived from sequences aligned to a population level or individual references) and/or non-aligned variables (e.g., sequence content). The features can be classified into different groups based on the underlying genetic data or intermediate values resulting from a processing of the underlying genetic data. Features can be selected from a feature space for creating a feature vector for training a model. The selection and creation of feature vectors can be performed iteratively to train many models as part of a search for optimal features and an optimal model.

A disposable cassette for detecting nucleic acids or performing other assays. The cassette can be inserted into a base station during use. The cassette has numerous features to ensure correct operation of the device under gravity, such as vent pockets for enabling the flow of sample fluid from one chamber to the next when the vent pocket is unsealed. The vent pockets have protrusions to help prevent accidental resealing. The cassette also can have a gasket to ensure free air movement between open vent pockets. A flexible circuit with patterned metallic electrical components disposed on a heat stable material can be in direct contact with fluid in the chambers and has resistive heating elements aligned with the vent pockets and the chambers. The detection chamber, which houses a lateral flow detection strip can have a space below the strip that has sufficient capacity to accommodate an entire volume of the sample fluid entering the detection chamber at a height that enables the fluid to flow up the detection strip by capillary action without flooding or otherwise bypassing regions of the detection strip. The space can also contain detection particles. Recesses in in the cassette channels or chambers can have structures such as ridges or grooves to direct fluid flow to enhance rehydration of lyophilized reagents disposed in the recess. Flow diverters in the chambers can reduce the flow velocity of the sample fluid and increase the effective fluid flow path length, enabling more accurate control of fluid flow in the cassette.

Systems, methods, and apparatuses for generating and using machine learning models using genetic data. A set of input features for training the machine learning model can be identified and used to train the model based on training samples, e.g., for which one or more labels are known. As examples, the input features can include aligned variables (e.g., derived from sequences aligned to a population level or individual references) and/or non-aligned variables (e.g., sequence content). The features can be classified into different groups based on the underlying genetic data or intermediate values resulting from a processing of the underlying genetic data. Features can be selected from a feature space for creating a feature vector for training a model. The selection and creation of feature vectors can be performed iteratively to train many models as part of a search for optimal features and an optimal model.

The present invention relates to methods for isolating nucleic acids present in a sample, in particular cell-free DNA (cfDNA) from a blood sample and polymers, substrates and kits for the method. Polymers with characteristics suitable to bind such nucleic acids are provided.