Abstract: The present disclosure relates to methods and compositions for enhanced assessment of exogenous polynucleotide and/or polypeptide-mediated transcriptional perturbations at high throughput and single cell/droplet levels of resolution. In embodiments, nucleic acid fusions of exogenous polynucleotide(s) and associated target transcript(s) are produced within individually sequestered or discretely identifiable cells/lysates and analyzed for exogenous polynucleotide mediated perturbations across a vast population of droplets/cells within individual reactions. Kits for performance of the methods are also provided.

Abstract: The present disclosure relates to compositions and methods for nucleic acid sequencing, and specifically, at least in certain aspects, provides methods and compositions for enhancing the efficacy, throughput and/or yield of known long-range sequencing platforms, by providing chimeric arrays of input sequences. Such arrays of component nucleic acid sequence elements can be prepared via methods that minimize introduction of bias. The application of the current methods to obtain isoform sequencing information, e.g., from patient samples is specifically also provided, as are methods for mitochondrial lineage tracing that employ the instant chimeric amplicon sequencing processes. Methods and systems for array nucleic acid sequence processing and interpretation are also provided.

Abstract: The present disclosure relates to compositions and methods for single-cell nucleic acid sequencing, and specifically provides for pre-amplifying target nucleic acids in a manner that allows for more proportionate detection of all target nucleic acids, including low prevalence/abundance RNAs, from individual cells. The disclosure also provides for application of a series of barcoding steps to associate cell-specific identifiers (IDs) to the targeted nucleotide sequences, and ultimately provides for increased throughput capacity and greater accuracy of single-cell nucleic acid sequencing. Certain aspects of the present disclosure also provide for improved quantitative detection of nucleic acid sequence barcodes, which in embodiments allows for highly sensitive quantitative detection of barcoded antibody levels and/or highly sensitive quantitative detection of barcoded antibody-bound protein levels (e.g.

Abstract: Disclosed herein are methods and platforms related to modulating expression of a gene of interest within a select population of cells comprising: providing a population of cells; providing a vehicle, plasmid, vector or recombinant virus, or equivalent thereof, capable of stably expressing a guide nucleic acid comprising randomized barcodes, thereby producing a population of barcoded cells; allowing said barcoded cell to divide, thereby forming a barcoded progeny of cells; saving an aliquot of cells; identifying the barcode in a lineage of interest from the barcoded progeny of cells; reconstituting the aliquot of saved cells, and transforming the reconstituted aliquot of cells with a transcriptional element comprising a transcriptional effector, the barcode of the lineage of interest, and a gene of interest; utilizing the transcriptional effector to modify expression of the gene of interest within the lineage of interest.