3D genome modeling
Project leaders: Philippe Collas and Jonas Paulsen
3D genome organization of the genom
e influences cell- and time-specific blueprints of gene expression. Some aspects of 3D genome conformation vary between cell types, su
ggesting developmental regulation – that is, regulation in a 4D space where the 4th component is time. 3D genome conformation entails interactions between chromosomes, forming interactions ‘hubs’ called topologically-associating domains (TADs). At the nuclear periphery, chromosomes interact with the nuclear lamina through lamin-associated domains (LADs). These interactions are dynamic during cell differentiation. For a recent review from our lab, see Sekelja et al. 2016 Genome Biol.
We are investigating links between cellular metabolism and changes in spatial genome conformation during differentiation of adipose stem cells in normal and pathological conditions.
Ongoing research:
- Computational methods for 3D and 4D modeling of genome architecture
- Functional relationships between 3D chromatin folding, nuclear envelope-chromatin interactions, epigenetic states and lineage-specific differentiation capacity
Recent achievements:
- Chrom3D genome structures in Virtual Reality (see our short video on Youtube)
- Chrom3D: a computational platform for 3D genome modeling from HiC and lamin-genome contacts (Paulsen et al 2017 Genome Biol 18:21)
- ChIP protocol for nuclear lamins (Oldenburg et al 2016 Meth Mol Biol 1411, 315-324)
- manifold-based optimization to enhance modeling of 3D chromatin structure from sparse HiC data (Paulsen et al 2015, PLoS Comput Biol 11, e1004396)
- EDD: a domain calling algorithm (Enriched Domain Detector; https://github.com/CollasLab/edd) to map LADs and other broad domains of enrichment from ChIP-seq data (Lund et al 2014 Nucl Acids Res 42, e92)