Some embodiments of the present invention relate to the enrichment of non-host nucleic acids in a mixture of host and non-host nucleic acids. Some embodiments include methods for detecting pathogenic organisms from a nucleic acid sample comprising host nucleic acids and nucleic acids indicative of the pathogenic organism.

Provided herein are methods for preparing a sequencing library that includes nucleic acids from a plurality of single cells. In one embodiment, the methods include linear amplification of the nucleic acids. In one embodiment, the sequencing library includes whole genome nucleic acids from the plurality of single cells. In one embodiment, the nucleic acids include three index sequences. Also provided herein are compositions, such as compositions that include the nucleic acids having three index sequences.

Provided herein are methods for preparing a sequencing library that includes nucleic acids from a plurality of single cells. In one embodiment, the methods include linear amplification of the nucleic acids. In one embodiment, the sequencing library includes whole genome nucleic acids from the plurality of single cells. In one embodiment, the nucleic acids include three index sequences. Also provided herein are compositions, such as compositions that include the nucleic acids having three index sequences.

Embodiments disclosed herein are directed to microfluidic devices that allow for scalable on-chip screening of combinatorial libraries and methods of use thereof. Droplets comprising individual molecular species to be screened are loaded onto the microfluidic device. The droplets are labeled by methods known in the art, including but not limited to barcoding, such that the molecular species in each droplet can be uniquely identified. The device randomly sorts the droplets into individual microwells of an array of microwells designed to hold a certain number of individual droplets in order to derive combinations of the various molecular species. The paired droplets are then merged in parallel to form merged droplets in each microwell, thereby avoiding issues associated with single stream merging. Each microwell is then scanned, e.g., using microscopy, such as high content imaging microscopy, to detect the optical labels, thereby identifying the combination of molecular species in each microwell.

A method of selecting nucleic acid samples including particular desired alleles from a plurality of nucleic acid samples including the steps of performing a first reaction in a plurality of pools containing the samples to produce reaction products including a source tag identifying said each pool; pooling the pools to provide pooled pools; for each of the desired alleles to be identified, performing a second reaction using said reaction products to produce allele-specific second reaction products comprising a marker tag and a derived source tag; identifying said allele-specific second reaction products, and further identifying nucleic acid samples with the desired alleles. A source tag sharing number d may be determined for each of the alleles. Alleles may also be binned together.

A method of selecting nucleic acid samples including particular desired alleles from a plurality of nucleic acid samples including the steps of performing a first reaction in a plurality of pools containing the samples to produce reaction products including a source tag identifying said each pool; pooling the pools to provide pooled pools; for each of the desired alleles to be identified, performing a second reaction using said reaction products to produce allele-specific second reaction products comprising a marker tag and a derived source tag; identifying said allele-specific second reaction products, and further identifying nucleic acid samples with the desired alleles. A source tag sharing number d may be determined for each of the alleles. Alleles may also be binned together.

Disclosed is a method for obtaining a bifunctional complex comprising a display molecule part and a coding part, wherein a nascent bifunctional complex comprising a chemical reaction site and a priming site for enzymatic addition of a tag is reacted at the chemical reaction site with one or more reactants, and provided with respective tag(s) identifying the reactant(s) at the priming site is using one or more enzymes.

Disclosed is a method for obtaining a bifunctional complex comprising a display molecule part and a coding part, wherein a nascent bifunctional complex comprising a chemical reaction site and a priming site for enzymatic addition of a tag is reacted at the chemical reaction site with one or more reactants, and provided with respective tag(s) identifying the reactant(s) at the priming site is using one or more enzymes.

A method of selecting nucleic acid samples including particular desired alleles from a plurality of nucleic acid samples including the steps of performing a first reaction in a plurality of pools containing the samples to produce reaction products including a source tag identifying said each pool; pooling the pools to provide pooled pools; for each of the desired alleles to be identified, performing a second reaction using said reaction products to produce allele-specific second reaction products comprising a marker tag and a derived source tag; identifying said allele-specific second reaction products, and further identifying nucleic acid samples with the desired alleles. A source tag sharing number d may be determined for each of the alleles. Alleles may also be binned together.

A method of selecting nucleic acid samples including particular desired alleles from a plurality of nucleic acid samples including the steps of performing a first reaction in a plurality of pools containing the samples to produce reaction products including a source tag identifying said each pool; pooling the pools to provide pooled pools; for each of the desired alleles to be identified, performing a second reaction using said reaction products to produce allele-specific second reaction products comprising a marker tag and a derived source tag; identifying said allele-specific second reaction products, and further identifying nucleic acid samples with the desired alleles. A source tag sharing number d may be determined for each of the alleles. Alleles may also be binned together.