Provided herein, in some embodiments, are compositions and methods for producing a molecular expression map of a biological sample using Deterministic Barcoding in Tissue for spatial omics sequencing (DBiT-seq).

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

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

Disclosed is a method for capturing the spatial molecular profiling of a biological mass formed from biological material, comprising the steps of: a) providing a transected biological mass, for example a tumour, the transection exposing at least a portion of the mass; b) providing a solid support of an area at least equalling the area of said portion of the mass; c) transferring biological material from the portion of the mass to the support to provide on the support a two dimensional imprint of the biological material present at the portion of the mass; and d) performing a biological assay of the transferred biological material from different predetermined locations of the imprint in order to determine the spatial molecular profile of the portion of the mass.

Disclosed is a method for capturing the spatial molecular profiling of a biological mass formed from biological material, comprising the steps of: a) providing a transected biological mass, for example a tumour, the transection exposing at least a portion of the mass; b) providing a solid support of an area at least equalling the area of said portion of the mass; c) transferring biological material from the portion of the mass to the support to provide on the support a two dimensional imprint of the biological material present at the portion of the mass; and d) performing a biological assay of the transferred biological material from different predetermined locations of the imprint in order to determine the spatial molecular profile of the portion of the mass.

The present disclosure relates to a method of sequencing nascent RNA in a cell. In some embodiments, the nascent RNA is conjugated to DNA using copper-catalyzed azide-alkyne cycloaddition (CuAAC). Methods of the present disclosure can be used to generate genomic libraries of a cell and measure gene expression and enhancer and/or super-enhancer activity.

The present disclosure relates to a method of sequencing nascent RNA in a cell. In some embodiments, the nascent RNA is conjugated to DNA using copper-catalyzed azide-alkyne cycloaddition (CuAAC). Methods of the present disclosure can be used to generate genomic libraries of a cell and measure gene expression and enhancer and/or super-enhancer activity.

Provided herein are methods for preparing biological samples for spatial proteomic analysis, methods of determining a location of a protein analyte in a biological sample, and methods of determining a location of a protein analyte and a nucleic acid analyte in a biological sample.

Provided herein are methods for preparing biological samples for spatial proteomic analysis, methods of determining a location of a protein analyte in a biological sample, and methods of determining a location of a protein analyte and a nucleic acid analyte in a biological sample.

Provided herein, in some embodiments, are methods and compositions for highly multiplexed in situ signal amplification via hairpin-mediated concatemerization.