Massachusetts Institute of Technology

Harvard College

University of Massachusetts

Whitehead Institute for Biomedical Research

Illumina Cambridge Limited

The Broad Institute, Inc.

The General Hospital Corporation

Instituto Carlos Slim De La Salud, A.c.

Andreas Gnirke

Alexandre Melnikov

Niall Anthony Gormley

Eric Lander

Job Dekker

Georgia Giannoukos

David Jaffe

Harris Nusbaum

Nynke Van Berkum

Chad Nusbaum

Louise Williams

Erez Lieberman Aiden

Erez Lieberman

Pardis Sabeti

Eric S Lander

Tarjei Mikkelsen

Mark Daly

Hayden Metsky

Andrew Kirby

Brendan Blumenstiel

Matthew Defelice

Christian Matranga

Daniel Aird

Daniel Park

Li Wang

Xiaolan Zhang

The invention relates to a method of preparing and using a library of template polynucleotides suitable for use as templates in solid-phase nucleic acid amplification and sequencing reactions to determine the methylation status of the cytosine bases in the library. In particular, the invention relates to a method of preparing and analysing a library of template polynucleotides suitable for methylation analysis.

Preparation of templates for methylation analysis

The disclosed Hi-C protocol can identify genomic loci that are spatially co-located in vivo. These spatial co-locations may include, but are not limited to, intrachromosomal interactions and/or interchromosomal interactions. Hi-C techniques may be applied to many different scales of interest. For example, on a large scale, Hi-C techniques can be used to identify long-range interactions between distant genomic loci.

HiC: method of identifying regulatory interactions between genomic loci

The invention provides methods for determining the activity of a plurality of nucleic acid regulatory elements. These methods may facilitate, e.g., the systematic reverse engineering, and optimization of mammalian cis-regulatory elements at high resolution and at a large scale. The method may include integration of multiplexed DNA synthesis and sequencing technologies to generate and quantify the transcriptional regulatory activity of e.g., thousands of arbitrary DNA sequences in parallel in cell-based as says (e.g., mammalian cell based assays).

Multiplexed genetic reporter assays and compositions

The present invention provides a combination of genomic and computational technologies to provide rapid, portable sample analysis for sequencing or identifying a target sequence involving generating probes for use in analyzing a sample which may comprise a target sequence.

Sample analysis, presence determination of a target sequence

The invention relates to a kit for preparing a library of template polynucleotides suitable for use as templates in solid-phase nucleic acid amplification and sequencing reactions to determine the methylation status of the cytosine bases in the library. In particular, the invention relates to a kit for preparing a library of template polynucleotides suitable for methylation analysis.

HiC: method of identifying interactions between genomic loci

The present invention features a highly sensitive assay for detecting frameshift mutations for high throughput use. Also provided herein are methods for diagnosing or determining a predisposition for developing medullary cystic kidney disease type 1 (MCKD1) in a subject by detecting a frameshift mutation in the GC-rich variable number of tandem repeats (VNTR) sequence of the mucin 1 gene (MUC-1).

Methods of diagnosing and treating medullary cystic kidney disease

The invention relates to a method of preparing and using a library of template polynucleotides suitable for use as templates in solid-phase nucleic acid amplification and sequencing reactions to determine the methylation status of the cytosine bases in the library. In particular, the invention relates to a method of preparing and analyzing a library of template polynucleotides suitable for methylation analysis.

Methods of identifying interactions between genomic loci

The present invention describes compositions and methods showing that the spatial proximity of intracellular components may be related to their ability to cooperate in intracellular biochemical reactions. In some embodiments, the present invention contemplates a variety of nucleic acid barcoded binding partners capable of determining the spatial proximity of intracellular components as determined by ligation of their respective nucleotide barcodes. As such, an intracellular component contact map may be constructed to fingerprint specific physiological and/or pharmacological intracellular conditions.

Parallel proximity ligation event analysis

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Wellesley, MA, United States of America

Andreas Gnirke