A method for generating region-specific amplification templates of a biological sample includes adding first oligonucleotide constructs and second oligonucleotide constructs to the biological sample. Each first or second oligonucleotide construct comprises a first or a second photoremovable cage molecule. The method further includes synthesising a complementary first strand from a template bound to target binding regions of each first oligonucleotide construct or each second oligonucleotide construct, scanning a first region of interest of the biological sample with a first focused light beam and a second region of interest of the biological sample with a second focused light beam to form uncaged first oligonucleotide constructs in the first region of interest and uncaged second oligonucleotide constructs in the second region of interest, synthesising a complementary second strand to form first amplification templates originating from the first region of interest and second amplification templates originating from the second region of interest.

A method for generating region-specific amplification templates of a biological sample includes adding first oligonucleotide constructs and second oligonucleotide constructs to the biological sample. Each first or second oligonucleotide construct comprises a first or a second photoremovable cage molecule. The method further includes synthesising a complementary first strand from a template bound to target binding regions of each first oligonucleotide construct or each second oligonucleotide construct, scanning a first region of interest of the biological sample with a first focused light beam and a second region of interest of the biological sample with a second focused light beam to form uncaged first oligonucleotide constructs in the first region of interest and uncaged second oligonucleotide constructs in the second region of interest, synthesising a complementary second strand to form first amplification templates originating from the first region of interest and second amplification templates originating from the second region of interest.

The present disclosure provides, inter alia, methods and compositions (e.g., conjugates) for imaging, at high spatial resolution, targets of interest.

The present disclosure provides, inter alia, methods and compositions (e.g., conjugates) for imaging, at high spatial resolution, targets of interest.

Provided herein is a method for analyzing genomic DNA In some embodiments, the method may comprise labeling a genomic sample by adding a capture tag to the ends of the DNA molecules in the sample and labeling molecules that comprise hydroxymethylcytosine with a first fluorophore, immobilizing the labeled DNA molecules on a support, and imaging individual molecules of hydroxymethylated genomic DNA on the support.

Provided herein is a method for analyzing genomic DNA In some embodiments, the method may comprise labeling a genomic sample by adding a capture tag to the ends of the DNA molecules in the sample and labeling molecules that comprise hydroxymethylcytosine with a first fluorophore, immobilizing the labeled DNA molecules on a support, and imaging individual molecules of hydroxymethylated genomic DNA on the support.

Disclosed herein are compositions and methods for detecting RNA binding sites and RNA interacting partners involving the use of a modified capture oligonucleotide having a dual toehold design.

Disclosed herein are compositions and methods for detecting RNA binding sites and RNA interacting partners involving the use of a modified capture oligonucleotide having a dual toehold design.

The disclosure provides methods for processing nucleic acid populations containing different forms (e.g., RNA and DNA, single-stranded or double-stranded) and/or extents of modification (e.g., cytosine methylation, association with proteins). These methods accommodate multiple forms and/or modifications of nucleic acid in a sample, such that sequence information can be obtained for multiple forms. The methods also preserve the identity of multiple forms or modified states through processing and analysis, such that analysis of sequence can be combined with epigenetic analysis.

The disclosure provides methods for processing nucleic acid populations containing different forms (e.g., RNA and DNA, single-stranded or double-stranded) and/or extents of modification (e.g., cytosine methylation, association with proteins). These methods accommodate multiple forms and/or modifications of nucleic acid in a sample, such that sequence information can be obtained for multiple forms. The methods also preserve the identity of multiple forms or modified states through processing and analysis, such that analysis of sequence can be combined with epigenetic analysis.