US 2019/0295684 A1Published application

Method and apparatus for analysis of chromatin interaction data

AssigneeThe Regents of the University of Michigan

InventorsAri Allyn-Feuer, Brian D. Athey, Gerald A. Higgins, Alex Ade

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Abstract

To analyze spatial organization of chromatin a computing device may compile genomic element contacts or reads into variable size bins using a binary search tree. The bins may be selected to each represent a different cutsite increment or functional element within a genome, such as a gene, TAD, chromatin state segment, loop domain, chromatin domain, etc. Two sets of bins are selected to generate a squared genome matrix of bin pairs, where each set represent an axis of the matrix. Then a normalization method is applied to the interaction frequencies for the bin pairs having variable size and/or shape to generate normalized interaction frequencies for each bin pair. The normalized interaction frequencies may be used to identify bin pairs having enriched and depleted contacts for a variety of analyses, including the detection of target genes of genomic variants, as well as genome wide analysis of contacts.

Claims20

Dependent claims

A computer-implemented method for analyzing spatial and temporal organization of chromatin, the method executed by one or more processors programmed to perform the method, the method comprising:

obtaining, at one or more processors, a set of pairwise contacts of genomic elements;
segmenting, by the one or more processors, genomic elements into a plurality of bins, wherein bin sizes for the plurality of bins are non-uniform;
identifying, by the one or more processors, a first set of the plurality of bins and a second set of the plurality of bins;
generating, by the one or more processors, a matrix of n×m bin pairs, wherein n corresponds to the first set of the plurality of bins and m corresponds to the second set of the plurality of bins;
identifying, by the one or more processors, a subset of pairwise contacts within each of the bin pairs;
determining, by the one or more processors, an interaction frequency for each of the bin pairs;
normalizing, by the one or more processors, each of the interaction frequencies to generate a normalized interaction frequency for each bin pair;
and
providing, by the one or more processors, a mapping of chromatin interactions for display on a user interface, including indications of the bin pairs and respective indications of normalized interaction frequencies.

6 more elements

A computing device for analyzing spatial and temporal organization of chromatin, the computing device comprising:

a communication network,
one or more processors;
and
a non-transitory computer-readable memory coupled to the one or more processors and storing thereon instructions that, when executed by the one or more processors, cause the computing device to:
obtain a set of pairwise contacts of genomic elements;
segment genomic elements into a plurality of bins, wherein bin sizes for the plurality of bins are non-uniform;
identify a first set of the plurality of bins and a second set of the plurality of bins;
generate a matrix of n×m bin pairs, wherein n corresponds to the first set of the plurality of bins and m corresponds to the second set of the plurality of bins;
identify a subset of pairwise contacts within each of the bin pairs;
determine an interaction frequency for each of the bin pairs;
normalize each of the interaction frequencies to generate a normalized interaction frequency for each bin pair;
and
provide, via the communication network, a mapping of chromatin interactions for display on a user interface, including indications of the bin pairs and respective indications of normalized interaction frequencies.

10 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/359,385Filed 20 Mar 2019
Priority: 22 Mar 2018
Published: 26 Sep 2019
Term ends: Not estimatedThe source records don’t support an estimate.

Classification5 codes

G16B 15/00
Ict specially adapted for analysing two-dimensional [2d] or three-dimensional [3d] molecular structures
G16B 45/00
Ict specially adapted for bioinformatics-related data visualisation
G16B 20/00
Ict specially adapted for functional genomics or proteomics
G16B 40/00
Ict specially adapted for biostatistics