Chromatin spatial structure

Ulianov et al. Genome Biology 2016

Methods to study chromatin structure

Microscopy:

Microscopy with fluorescing marks:
(FISH)

For 2 marks:

For multiple marks:

Chromatin conformation capture

3C: Dekker et al. Science 2002

Hi-C

Viewpoint

High-throughput chromosomes conformation capture:

DNA interactome map:

Lieberman-Aiden et al. Science 2009

Chromatin spatial structure

Adopted from Imakaev et al. Nature Methods 2012

Chromosome territories

Bonev et al. Nature Reviews 2016

TADs

Bonev et al. Nature Reviews 2016

Compartments of chromatin

Bonev et al. Nature Reviews 2016

Loops of chromatin

Bonev et al. Nature Reviews 2016

The importance of TADs and loops

Lupiáñez et al., Cell, 2015

TADs

Filippova et al. Algorithms for Molecular Biology 2014

TADs are hierarchical, there is no single solution for the TAD calling problem:

• Armatus is one of the programs trying to solve this problem.
• Armatus is based on a dynamic programming algorithm that has an adjustable parameter.

TADs callers comparison

Forcato et al. Nature Methods 2017

Functional annotation problem

Example of association of complex datasets:

Stackup plot

Stackup plot

Plotting the profiles of enrichment around TAD boundaries (ChIP-Seq):

Functional annotation of the boundaries

Task: 

1. Download bigwig-файл for the factor you like from ENCODE. Good candidates are CTCF, Chriz, Su(Hw) and the one below.
   Use the link for selection and download:

Get the resulting link:
https://www.encodeproject.org/files/ENCFF637XEP/@@download/ENCFF637XEP.bigWig

Download the annotation:

! wget https://www.encodeproject.org/files/ENCFF637XEP/@@download/ENCFF637XEP.bigWig

Import the package: 

 import bbi

Create the stack: 

stackup = bbi.stackup('ENCFF637XEP.bigWig',TADs_clustering.ch,TADs_clustering.bgn-20000,TADs_clustering.bgn+20000, bins=20)

Plot the stack: 

import seaborn as sns
sns.heatmap(stackup, cmap='RdBu_r')

and enrichment:  

plt.plot(stackup.sum(axis=0))

Функциональная аннотация границ

Самостоятельные задачки: 

1. Скачать bigwig-файл для понравившегося фактора с ENCODE. Хорошие кандидаты: CTCF, Chriz, Su(Hw) и ниже.
   Воспользуйтесь ссылкой для выбора и скачивания

Получите итоговую ссылку. Она должна иметь вид: https://www.encodeproject.org/files/ENCFF637XEP/@@download/ENCFF637XEP.bigWig

Скачаем аннотацию: 

! wget https://www.encodeproject.org/files/ENCFF637XEP/@@download/ENCFF637XEP.bigWig

Импортируем библиотеку: 

 import bbi

Построим стек: 

stackup = bbi.stackup('ENCFF637XEP.bigWig',TADs_clustering.ch,TADs_clustering.bgn-20000,TADs_clustering.bgn+20000, bins=20)

Нарисуем стек: 

import seaborn as sns
sns.heatmap(stackup, cmap='RdBu_r')

и обогащение:  

plt.plot(stackup.sum(axis=0))

Theory of epigenetic coding

Chromatin in development

Chromatin as a graph