Abstract: The present disclosure relates to compositions and methods for assessing relative DNA levels (e.g., levels of genomic DNA, mtDNA, viral DNA, bacterial DNA, etc.) in a spatially-defined manner across a tissue sample, specifically providing DNA sequence identity and relative abundance information at high-resolution across multiple locations assessed across the tissue sample.

Abstract: Embodiments disclosed herein provide methods of using somatic mutations in mitochondrial genomes to retrospectively infer cell lineages in native contexts and to serve as genetic barcodes to measure clonal dynamics in complex cellular populations. Further, somatic mutations in mitochondrial DNA (mtDNA) are tracked by single cell genomic approaches for simultaneous analysis of single cell lineage and state. Applicants further show that mitochondrial mutations can be readily detected with contemporary single cell transcriptomic and epigenomic technologies to concomitantly capture gene expression profiles and chromatin accessibility, respectively.

Abstract: Methods for labeling and imaging the accessible genome using a transposase are disclosed. In some embodiments, a bifunctional transposase complex or transposome is used to insert adaptors comprising chemical tags selectively at accessible sites in the genome where active regulatory DNA is located. Various chemical tags can be used for labeling DNA at insertion sites, including, for example, fluorescent dyes for fluorescence imaging, metal particles for electron microscopy or magnetic manipulation of DNA, isotopic labels, or biotin or other ligands, haptens, substrates, or inhibitors that are recognized by streptavidin, antibodies, enzymes, or receptors. Labeling DNA in this manner can be used to provide spatial information regarding the positioning of regulatory DNA in the genome and makes possible the imaging and sorting of cells based on the status of their regulatory DNA.

Abstract: Certain embodiments provide a method for capturing a genomic fragment. The method may comprise: obtaining a substrate comprising a first population of surface-bound oligonucleotides and a second population of surface-bound oligonucleotides; hybridizing a first member of the first population of surface-bound oligonucleotides to a selection oligonucleotide comprising a region that hybridizes with the first member and a region that contains a genomic sequence; extending the first member of the first population of surface-bound oligonucleotides to produce a support-bound selection primer that comprises a sequence that is complementary to the genomic sequence; hybridizing the support-bound selection primer to a nucleic acid fragment comprising the genomic sequence; extending the support-bound selection primer to produce an extension product that contains a sequence that flanks the genomic sequence, e.g., in a genome; and amplifying the extension product on the substrate.

Abstract: Certain embodiments provide a method for capturing a genomic fragment. The method may comprise: obtaining a substrate comprising a first population of surface-bound oligonucleotides and a second population of surface-bound oligonucleotides; hybridizing a first member of the first population of surface-bound oligonucleotides to a selection oligonucleotide comprising a region that hybridizes with the first member and a region that contains a genomic sequence; extending the first member of the first population of surface-bound oligonucleotides to produce a support-bound selection primer that comprises a sequence that is complementary to the genomic sequence; hybridizing the support-bound selection primer to a nucleic acid fragment comprising the genomic sequence; extending the support-bound selection primer to produce an extension product that contains a sequence that flanks the genomic sequence, e.g., in a genome; and amplifying the extension product on the substrate.