This disclosure provides methods and kits useful in analysis of mixed nucleic acid populations, including for multiplex genotyping of a mixed nucleic acid sample and for detecting differences in copy number of a target polynucleotide and/or a target chromosome (e.g., microdeletions, duplications and aneuploidies). The disclosure also provides methods and systems useful in the diagnosis of genetic abnormalities in a mixed nucleic acid population taken non-invasively from an organism, such as a sample of blood, plasma, serum, urine stool or saliva. The disclosed methods and systems find use in multiple applications, including prenatal testing and cancer diagnostics. The method is based on the hybridisation of amplified fragments obtained from the sample, e.g. using molecular inversion probes (MIP) to an oligonucleotide array and the detection of the alleles based on different signals from the different alleles of the SNP.

This disclosure provides methods and kits useful in analysis of mixed nucleic acid populations, including for multiplex genotyping of a mixed nucleic acid sample and for detecting differences in copy number of a target polynucleotide and/or a target chromosome (e.g., microdeletions, duplications and aneuploidies). The disclosure also provides methods and systems useful in the diagnosis of genetic abnormalities in a mixed nucleic acid population taken non-invasively from an organism, such as a sample of blood, plasma, serum, urine stool or saliva. The disclosed methods and systems find use in multiple applications, including prenatal testing and cancer diagnostics. The method is based on the hybridisation of amplified fragments obtained from the sample, e.g. using molecular inversion probes (MIP) to an oligonucleotide array and the detection of the alleles based on different signals from the different alleles of the SNP.

Methods for determining a location of a feature on an array include: (a) providing a first array with a first plurality of features immobilized on a first substrate; (b) providing a second array with a second plurality of features immobilized on a second substrate; (c) aligning the first array with the second array; (d) hybridizing a first barcoded oligonucleotide of the first array to a second barcoded oligonucleotide of the second array, thereby producing a combined nucleic acid that includes first and second spatial barcodes; (e) determining all or a portion of the sequence of the combined nucleic acid; and (f) identifying the second barcoded oligonucleotide associated with the first barcoded oligonucleotide in the combined nucleic acid, and determining the location of a second feature in the second array.

Methods for determining a location of a feature on an array include: (a) providing a first array with a first plurality of features immobilized on a first substrate; (b) providing a second array with a second plurality of features immobilized on a second substrate; (c) aligning the first array with the second array; (d) hybridizing a first barcoded oligonucleotide of the first array to a second barcoded oligonucleotide of the second array, thereby producing a combined nucleic acid that includes first and second spatial barcodes; (e) determining all or a portion of the sequence of the combined nucleic acid; and (f) identifying the second barcoded oligonucleotide associated with the first barcoded oligonucleotide in the combined nucleic acid, and determining the location of a second feature in the second array.

Presently described are compositions and methods for performing genome-wide enrichment of DNA microsatellites (e.g., homopolymers) containing deletions and facilitating their detection via sequencing or other downstream methodologies. Additionally, disclosed herein are compositions and methods for selecting the genomic fraction containing poly-adenine/poly-thymidine homopolymer repeats and other A:T-rich sequences of low melting temperature from the genome, so that very little sequencing is required to detect the enriched homo-polymer deletions.

Presently described are compositions and methods for performing genome-wide enrichment of DNA microsatellites (e.g., homopolymers) containing deletions and facilitating their detection via sequencing or other downstream methodologies. Additionally, disclosed herein are compositions and methods for selecting the genomic fraction containing poly-adenine/poly-thymidine homopolymer repeats and other A:T-rich sequences of low melting temperature from the genome, so that very little sequencing is required to detect the enriched homo-polymer deletions.

Methods for the rapid detection of the presence of variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that contain mutations in the Spike (S) protein gene in a biological or non-biological sample are described. The methods can include performing an amplifying step, a hybridizing step, and a detecting step. Furthermore, primers and probes targeting SARS-CoV-2 variants containing S gene mutations and kits are provided that are designed for the detection of SARS-CoV-2 variants containing S gene mutations.

Methods for the rapid detection of the presence of variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that contain mutations in the Spike (S) protein gene in a biological or non-biological sample are described. The methods can include performing an amplifying step, a hybridizing step, and a detecting step. Furthermore, primers and probes targeting SARS-CoV-2 variants containing S gene mutations and kits are provided that are designed for the detection of SARS-CoV-2 variants containing S gene mutations.

The invention generally relates to droplet based digital PCR and methods for analyzing a target nucleic acid using the same. In certain embodiments, methods of the invention involve forming sample droplets containing, on average, a single target nucleic acid, amplifying the target in the droplets, excluding droplets containing amplicon from the target and amplicon from a variant of the target, and analyzing target amplicons.

The invention generally relates to droplet based digital PCR and methods for analyzing a target nucleic acid using the same. In certain embodiments, methods of the invention involve forming sample droplets containing, on average, a single target nucleic acid, amplifying the target in the droplets, excluding droplets containing amplicon from the target and amplicon from a variant of the target, and analyzing target amplicons.