TimelessFlex - A flexible framework for investigating chromatin state trajectories

by Henriette Miko (henriette.miko@mdc-berlin.de), Ohler lab at BIMSB/MDC, 2020

Framework description

TimelessFlex is a flexible framework for investigating chromatin state trajectories during linear and branched tissue differentiation. This framework adapts and extends Timeless, a Bayesian network for co-clustering of multiple histone modifications at promoter and enhancer feature regions. TimelessFlex is flexible depending on the available genomic data. The basic required data is ChIP-seq for histone modifications with at least three time points and a set of regions of interest.

The framework consists of three parts:

1. Regions definition:
   • combine ATAC-seq peaks over multiple time points into one set of open chromatin regions
   • define promoters and enhancers from open chromatin regions
   • if Hi-C data is available, assign promoters and enhancers to Hi-C interaction pairs
   • define feature regions around promoters and enhancer
2. Clustering:
   • compute histone mark signals over feature regions
   • cluster histone mark signals with Bayesian network
3. Validation and interpretation:
   • validate clusters with genomic data not used in clustering
   • functional analyses of clusters

Implementation details

This framework is written in R and bash and it makes use of multiple publicly available bioinformatics software. The clustering is performed in MATLAB with the Bayes Net Toolbox (BNT).

Repository structure

Code for data from mouse hematopoiesis

All code for processing and analyzing data from mouse hematopoiesis at 6 time points (CMP, MEP, EryA, GMP, Granu, Mono) can be found in mouse_hematopoiesis.

Code for data from human pancreatic differentiation

All code for processing and analyzing data from human pancreatic differentiation at 5 time points D0, D2, D5, D7 and D10 can be found in human_pancreatic_differentiation.

Code for Miko et al. paper

All relevant code for Miko, H. et al., "Inferring time series chromatin states for promoter-enhancer pairs based on Hi-C data", BMC Genomics (2021) can be found in Miko_et_al_paper. This code is basically a subset of mouse_hematopoiesis and human_pancreatic_differentiation.