Abstract: 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.

Abstract: The present invention is related to a method for recovering two or more genes, or gene products, or cDNAs, encoding for an immunoreceptor having two or more subunits, which two or more genes, or gene products, are comprised in a given source cell. The invention is further related to a method of creating a library of expressor cells, in which library each cell is capable of expressing two or more genes, or gene products, encoding for the subunits of the immunoreceptor. The invention is further related to a method of screening a library of expressor cells as created according to the above method, for one cell that expresses an immunoreceptor that has specificity for a given target molecule.

Abstract: The disclosed methods and kits are useful in processing and analyzing a multiplicity of samples in molecular biology workflows where there is an increased chance for sample cross-contamination or misidentification. Some embodiments of the methods and kits utilize at least one spike in control and at least one barcode per sample.

Abstract: Methods and compositions are described for single cell resolution, quantitative proteomic analysis using high throughput sequencing.

Abstract: Disclosed herein include systems, methods, compositions, and kits for associating single cell sequencing data with phenotypic data and/or agent exposure. In some embodiments, cell indexing oligonucleotides comprising cell indexing sequences are associated with cells. In some embodiments, synthetic particles are associated with stochastic labels comprising cell indexing sequences. Sequential hybridizing and imaging of probes annealing to a cell indexing sequence can generate a spatial index. The spatial index can be employed to identify of the partition from which a sequenced nucleic acid target molecule originated.

Abstract: In one aspect, the present invention relates to a method for obtaining structural information about an encoded molecule. The encoded molecule may be produced by a reaction of a plurality of chemical entities and may be capable of being connected to an identifier oligonucleotide containing codons informative of the identity of the chemical entities which have participated in the formation of the encoded molecule. In a certain embodiment, primers are designed complementary to the codons appearing on the identifier oligonucleotide, and the presence, absence or relative abundance of a codon is evaluated by mixing a primer with the identifier oligonucleotide in the presence of a polymerase and substrate (deoxy)ribonucleotide triphosphates measuring the extension reaction. In another aspect, the invention provides a method for selecting compounds which binds to a target.

Abstract: Methods of evaluating or providing a clonal profile of a subject interval, e.g., a subgenomic interval, or an expressed subgenomic interval (or of a cell containing the same), in a subject, are disclosed.

Abstract: Methods of double-stranded nucleic acid sequence determination and assembly that are able to identify insertions, deletions, repeat region sizes and genomic rearrangements, for example, are disclosed herein, which can use relatively large labeled nucleic acid fragments to analyze the structure of even larger genetic regions. In some embodiments these methods involve the use of certain parameters which unexpectedly improve overall method performance. In some embodiments these methods involve sample labeling that does not result in the formation of single-stranded nucleic acid fragment labeling intermediaries.

Abstract: The present disclosure provides methods for selectively tagging 5-methylcytosine in a DNA sample and using this approach for genome-wide profiling of 5-methylcytosine in a low input DNA sample such as circulating cell-free DNA.

Abstract: The present invention provides ribosomal RNA origami nanostructures and in particular nanostructures comprising RNA staples, composition comprising such origami nanostructures as well as methods for manufacturing such origami structures.

Abstract: Methods, devices, and systems for performing digital assays are provided. In certain aspects, the methods, devices, and systems can be used for the amplification and detection of nucleic acids. In certain aspects, the methods, devices, and systems can be used for the recognition, detection, and sizing of droplets in a volume. Also provided are compositions and kits suitable for use with the methods and devices of the present disclosure.

Abstract: Provided herein are methods, compositions, and kits for assays, many of which involve amplification reactions such as digital PCR or droplet digital PCR. The assays may be used for such applications as sequencing, copy number variation analysis, and others. In some cases, the assays involve subdividing a sample into multiple partitions (e.g., droplets) and merging the partitions with other partitions that comprise adaptors with barcodes.

Abstract: A microfluidic lab-on-a-chip system for DNA gene assembly that utilizes a DNA symbol library and a DNA linker library. The lab-on-a-chip has a fluidic platform with a plurality of arrays operably connected to a voltage source and a controller for the voltage source, a set of first inlets operably connected to the fluidic platform, each first inlet for one DNA symbol from a DNA symbol library, a set of second inlets operably connected to the fluidic platform, each second inlet for one DNA linker from a DNA linker library, and a mixing area operably connected to the fluidic platform and to the plurality of first inlets and the plurality of second inlets.

Abstract: This invention generally relates to methods and systems for dispensing a droplet, in particular a picolitre volume droplet containing one or more entities.

Abstract: Provided herein are compositions and methods for detecting the binding of a peptide to an MHC molecule, and the binding of a peptide:MHC complex to a TCR. In preferred embodiments, the compositions and methods are in a highly-multiplexed way. The compositions and methods disclosed herein can be used to provide direct information on which peptides are bound to an MHC molecule. Also provided is a method for simultaneously detecting a large number of peptides for binding to an MHC molecule and/or a T cell. A method for detecting competitive binding of a large number of peptides to an MHC molecule and/or a T cell is also disclosed. Also provided herein is a method for simultaneously detecting a large number of specific TCRs. The compositions and methods of the present invention are useful for vaccine design, research and monitoring of autoimmune and infectious disease, immunogenicity testing of therapeutics, and tissue typing.

Abstract: This disclosure relates to new assay methods for analysis of circulating tumor cells (CTCs) in blood samples for detection, e.g., early detection, and/or monitoring of disease, e.g., cancer. The methods provide ultra-high sensitivity and specificity, and include the use of microfluidic isolation of CTCs and digital detection of RNA derived from the CTCs.

Abstract: System, including methods and apparatus, for spacing droplets from each other and for detection of spaced droplets.

Abstract: The present invention is directed to methods, compositions and systems for analyzing sequence information while retaining structural and molecular context of that sequence information.

Abstract: The invention relates to a device (1) for generating droplets (30) comprising a plurality of channels (20), wherein each channel (20) extends from an inlet (201) along a respective longitudinal axis (L) to an outlet (202), wherein said device (1) comprises a plurality of layers (10) of a substrate material arranged in a stack (100), wherein each layer (10) comprises a first side (101) and a second side (102) facing away from each other, and wherein said first side (101) of each layer (10) comprises a plurality of grooves (103), wherein said channels (20) are formed by said grooves (103) of said first side (101) of a respective layer (10) of said stack (100) and said second side (102) of a respective adjacent layer (10) of said stack (100). The invention further relates to a method for generating droplets (30) and a fabrication method of the device (1).

Abstract: The disclosed embodiments concern methods, apparatus, systems and computer program products for determining sequences of interest using unique molecular index (UMI) sequences that are uniquely associable with individual polynucleotide fragments, including sequences with low allele frequencies and long sequence length. In some implementations, the UMIs include both physical UMIs and virtual UMIs. In some implementations, the unique molecular index sequences include non-random sequences. System, apparatus, and computer program products are also provided for determining a sequence of interest implementing the methods disclosed.