10x Genomics, Inc.

Spatial Transcriptomics Ab

Spatial Transcriptomics Ab and Illumina, Inc.

Illumina Corporation

10x Genomics Sweden Ab

Patrik Ståhl

Joakim Lundeberg

Alex Aravanis

Jonas Frisen

Gordon M Cann

Leila Bazargan

Jonas Frisén

Pelin Sahlén

Fredrik SALMÉN

Sanja Vickovic

In some embodiments described herein are methods performed in situ for analyzing chromatin interaction events in a cell or in cells of a sample such as a non-homogenized tissue sample. The methods can comprise the spatial analysis of chromatin interaction events across cell populations in a biological sample. The methods can further comprise obtaining a biological sample, hybridizing probes to target nucleic acid sequences involved in chromatin interaction events and producing a nucleic acid sequence comprising all or part of the target nucleic acid sequences, amplifying the nucleic acid sequence so produced and detecting the amplified nucleic acid sequence in situ.

In situ analysis of chromatin interaction

A method for spatially tagging nucleic acids of a biological specimen, including steps of (a) providing a solid support comprising different nucleic acid probes that are randomly located on the solid support, wherein the different nucleic acid probes each includes a barcode sequence that differs from the barcode sequence of other randomly located probes on the solid support; (b) performing a nucleic acid detection reaction on the solid support to locate the barcode sequences on the solid support; (c) contacting a biological specimen with the solid support that has the randomly located probes; (d) hybridizing the randomly located probes to target nucleic acids from portions of the biological specimen; and (e) modifying the randomly located probes that are hybridized to the target nucleic acids, thereby producing modified probes that include the barcode sequences and a target specific modification, thereby spatially tagging the nucleic acids of the biological specimen.

Spatially distinguished, multiplex nucleic acid analysis of biological specimens

The present invention relates to methods and products for the localized or spatial detection of nucleic acid in a tissue sample and in particular to a method for localized detection of nucleic acid in a tissue sample comprising: (a) providing an array comprising a substrate on which multiple species of capture probes are directly or indirectly immobilized such that each species occupies a distinct position on the array and is oriented to have a free 3' end to enable said probe to function as a primer for a primer extension or ligation reaction, wherein each species of said capture probe comprises a nucleic acid molecule with 5&#x2032; to 3&#x2032;: (i) a positional domain that corresponds to the position of the capture probe on the array, and (ii) a capture domain; (b) contacting said array with a tissue sample such that the position of a capture probe on the array may be correlated with a position in the tissue sample and allowing nucleic acid of the tissue sample to hybridize to the capture domain in said capture probes; (c) generating DNA molecules from the captured nucleic acid molecules using said capture probes as extension or ligation primers, wherein said extended or ligated DNA molecules are tagged by virtue of the positional domain; (d) optionally generating a complementary strand of said tagged DNA and/or optionally amplifying said tagged DNA; (e) releasing at least part of the tagged DNA molecules and/or their complements or amplicons from the surface of the array, wherein said part includes the positional domain or a complement thereof; and (f) directly or indirectly analyzing the sequence of the released DNA molecules.

Method and product for localized or spatial detection of nucleic acid in a tissue sample

Growing community of inventors

Stockholm, Sweden

Patrik Ståhl