Provided herein are methods and composition for processing samples that contain nucleic acids, or cells containing nucleic acids, of a microbiome, using amounts of primers within a range of mole values and rounds of polymerase chain reaction (PCR) within a range of numbers of rounds.

This disclosure provides for devices, methods, and systems for performing a non-invasive prenatal testing (NIPT) digital assay upon generating at least a large number of counts per chromosome for a set of chromosomes present in a sample, where performing the NIPT digital assay can include: distributing nucleic acids of the sample and materials for an amplification reaction across a plurality of partitions; amplifying the nucleic acids with the materials, within the plurality of partitions; and generating counts per chromosome upon detecting signals from the plurality of partitions. The inventions enable processing of samples for NIPT digital analyses and/or other digital analyses involving other loci of interest, with unprecedented partitioning, reaction, readout, and analytical performance.

Methods and devices for cell-free sorting and cloning of nucleic acid libraries are provided herein.

Methods and devices for cell-free sorting and cloning of nucleic acid libraries are provided herein.

This disclosure provides, among other things, a reagent system for nucleic acid analysis. In some embodiments, the system may comprise a plurality of oligonucleotide sets each set comprising at least (a) a competitor oligonucleotide that hybridizes to a target sequence and varies in concentration from mixture to mixture and (b) a detector oligonucleotide that also hybridizes to the target sequence and contains a barcode that indicates the concentration of the competitor oligonucleotide in the oligonucleotide set. The reagent system may be used to analyze a nucleic acid sample.

This disclosure provides, among other things, a reagent system for nucleic acid analysis. In some embodiments, the system may comprise a plurality of oligonucleotide sets each set comprising at least (a) a competitor oligonucleotide that hybridizes to a target sequence and varies in concentration from mixture to mixture and (b) a detector oligonucleotide that also hybridizes to the target sequence and contains a barcode that indicates the concentration of the competitor oligonucleotide in the oligonucleotide set. The reagent system may be used to analyze a nucleic acid sample.

Embodiments relate to the preparation of nucleic acid libraries. Some embodiments relate to the preparation of normalized nucleic acid libraries, such as libraries in which the amounts of amplified nucleic acids are substantially the same for different amounts of input nucleic acids. Some embodiments relate to preparation of indexed nucleic acid libraries with certain adaptors.

Embodiments relate to the preparation of nucleic acid libraries. Some embodiments relate to the preparation of normalized nucleic acid libraries, such as libraries in which the amounts of amplified nucleic acids are substantially the same for different amounts of input nucleic acids. Some embodiments relate to preparation of indexed nucleic acid libraries with certain adaptors.

The present disclosure provides a method for enriching for multiple genomic regions using a first bait set that selectively hybridizes to a first set of genomic regions of a nucleic acid sample and a second bait set that selectively hybridizes to a second set of genomic regions of the nucleic acid sample. These bait set panels can selectively enrich for one or more nucleosome-associated regions of a genome, said nucleosome-associated regions comprising genomic regions having one or more genomic base positions with differential nucleosomal occupancy, wherein the differential nucleosomal occupancy is characteristic of a cell or tissue type of origin or disease state.

The present disclosure provides a method for enriching for multiple genomic regions using a first bait set that selectively hybridizes to a first set of genomic regions of a nucleic acid sample and a second bait set that selectively hybridizes to a second set of genomic regions of the nucleic acid sample. These bait set panels can selectively enrich for one or more nucleosome-associated regions of a genome, said nucleosome-associated regions comprising genomic regions having one or more genomic base positions with differential nucleosomal occupancy, wherein the differential nucleosomal occupancy is characteristic of a cell or tissue type of origin or disease state.