The Broad Institute, Inc.

Baylor College of Medicine

Harvard College

Massachusetts Institute of Technology

Elena Stamenova

Eric Lander

Erez Lieberman Aiden

Eric S Lander

Mitchell Guttman

Suhas Rao

Olga Dudchenko

Christopher Lui

Aviva Aiden

Arina Omer

Maxim Massenkoff

Sanjit Singh Batra

Sarah Nyquist

Per Aspera Adastra

Neva Durand

Erez Lieberman-Aiden

Anthony Tzen

Melanie Pham

Embodiments provide a method for sequencing and assembling long DNA genomes comprising generating a 3D contact map of chromatin loop structures in a target genome, the 3D contact map of chromatin loop structures defining spatial proximity relationships between genomic loci in the genome, and deriving a linear genomic nucleic acid sequence from the 3D map of chromatin loop structures.

Linear genome assembly from three dimensional genome structure

Disclosed are methods for detecting spatial proximity relationships between nucleic acid sequences in a cell. The methods include: providing a sample of one or more cells comprising nucleic acids; fragmenting the nucleic acids present in the cells, wherein the fragmented nucleic acids have ends capable of joining to other fragmented nucleic acids; joining ends of fragmented nucleic acids to other ends fragmented nucleic acid to create at least one nucleic acid concatemer having at least one junction between the joined fragmented nucleic acids, and wherein the at least one nucleic acid concatemer encodes the information about the proximity of the DNA sequences in the cell; and determining the sequence at least one junction of the at least one nucleic acid concatemer, thereby detecting spatial proximity relationships between nucleic acid sequences in a cell.

Methods of determining multiple interactions between nucleic acids in a cell

Disclosed is an in situ method for detecting spatial proximity relationships between nucleic acid sequences, such as DNA, in a cell. The method includes: providing a sample of one or more cells comprising nucleic acids; fragmenting the nucleic acids present in the cells that leaves 5' overhanging ends; filling in the overhanging ends with at least one labeled nucleotide; joining the filled in end of the fragmented nucleic acids that are in close physical proximity to create one or more end joined nucleic acid fragments having a junction; isolating the one or more end joined nucleic acid fragments using the labeled nucleotide; and determining the sequence at the junction of the one or more end joined nucleic acid fragments.

Method for in situ determination of nucleic acid proximity

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Reading, MA, United States of America

Elena Stamenova