Harvard College

Massachusetts Institute of Technology

Readcoor, LLC

Other

Evan R Daugharthy

George M Church

Richard C Terry

Je-Hyuk Lee

Edward Stuart Boyden

Fei Chen

Benjamin W Pruitt

Shahar Alon

Adam H Marblestone

Asmamaw T Wassie

Chao-ting Wu

Paul Warren Tillberg

Son C Nguyen

Jehyuk Lee

Jonathan Scheiman

Andrew C Payne

Michele A Busby

Daniel Goodwin

Brian M Turczyk

Methods of labelling one or more subcellular components (e.g., an organelle and/or subcellular region) in vivo are provided. Methods of labelling a protein in vivo are provided. Methods of determining a nucleic acid sequence in situ are also provided.

Methods for high-throughput labelling and detection of biological features in situ using microscopy

Methods of selectively sequencing amplicons in a biological sample are provided.

Method of selectively sequencing amplicons in a biological sample

The present disclosure provides methods and systems for analyzing a biological sample from a subject, comprising using probes to identify and determine the location of different genetic sequences.

Methods and systems for spatial mapping of genetic variants

The present disclosure provides methods and systems for generating and using indices in a synthetic three-dimensional (3D) matrix within a biological sample (e.g., a cell or a tissue sample). The present disclosure provides a method for processing or analyzing a nucleic acid molecule having a three-dimensional (3D) spatial position in a cell or cell derivative can comprise: (a) using a transposase to insert a nucleic acid index sequence into the nucleic acid molecule to generate an indexed nucleic acid molecule comprising the nucleic acid index sequence; (b) detecting the nucleic acid index sequence of the indexed nucleic acid molecule to identify the 3D spatial position; (c) subsequent to (b), removing the indexed nucleic acid molecule or derivative thereof from the 3D spatial position; and (d) identifying a sequence of the indexed nucleic acid molecule or derivative thereof removed from the 3D spatial position in (c).

Three-dimensional spatial molecular indexing

The disclosure provides a method for detecting a target analyte in a biological sample including contacting the sample with one or more probe sets each comprising a primary probe and a linker, contacting the sample with an initiator sequence, contacting the sample with a plurality of fluorescent DNA hairpins, wherein the probe binds the target molecule, the linker connects the probe to the initiator sequence, and wherein the initiator sequence nucleates with the cognate hairpin and triggers self-assembly of tethered fluorescent amplification polymers, and detecting the target molecule by measuring fluorescent signal of the sample.

Hybridization chain reaction methods for in situ molecular detection

The present invention relates to a method of identifying a target genomic nucleic acid sequence including hybridizing a set of probes to the target genomic nucleic acid sequence, wherein the set of probes has a unique associated barcode sequence for identification of the target genomic nucleic acid sequence, wherein each probe of the set includes (1) a complementary sequence complementary to a first strand of the target genomic nucleic acid sequence and (2) the associated barcode sequence or a portion of the associated barcode sequence, sequencing the associated barcode sequence from probes hybridized to the target genomic nucleic acid sequence using a fluorescence-based sequencing method, and identifying the target genomic nucleic acid sequence by the sequenced barcode sequence.

Methods for detecting and identifying genomic nucleic acids

Methods of volumetric imaging of a three-dimensional matrix of nucleic acids within a cell is provided. An automated apparatus for sequencing and volumetric imaging of a three-dimensional matrix of nucleic acids is provided.

Method and apparatus for volumetric imaging

The present disclosure provides methods that combine RNA fluorescent in situ sequencing (FISSEQ) with other molecular detection modalities, forming an integrated panomic detection platform. In various embodiments, the present disclosure provides systems and methods to prepare a biological sample to preserve the spatial relationships of biomolecules of interest within the biological sample for FISSEQ detection.

Methods of combining the detection of biomolecules into a single assay using fluorescent in situ sequencing

Methods of making a three-dimensional matrix of nucleic acids within a cell is provided.

Method for generating a three-dimensional nucleic acid containing matrix

The present disclosure provides methods and systems for detecting nucleic acid sequences in a biological sample having a three-dimensional matrix. The present disclosure also provides methods and systems for processing a biological sample for use in nucleic acid sequence detection.

Methods and systems for sample processing or analysis

Method and apparatus for volumetric imaging of a three-dimensional nucleic acid containing matrix

Compositions and methods for analyte detection

The present disclosure provides a number of targeted nucleic acid FISSEQ library construction methods. Targeted FISSEQ can exhibit several benefits, such as enhanced sensitivity and/or shorter assay time in the detection, identification, quantification, and/or determining the nucleotide sequence of the target species, relative to 'random' or 'whole-omic' detection via FISSEQ.

Growing community of inventors

Cambridge, MA, United States of America

Evan R Daugharthy