[BBC] [Gtpb] Clarification about the CSDM training course

Thu Nov 14 18:47:01 CET 2013

Dear All

It may be useful to provide further explanations about the content of  
the upcoming CSDM13 - Chromosome structure determination using  
modelling and Hi-C data - training course. I spoke with several people  
that questioned me about its usefulness in evolution studies, for  
example. The following text is an attempt to correct this.

    IMPORTANT DATES for this Course
    Deadline for applications: November 20th 2013
    Notification of acceptance within 72 hours of application (working  
days count)
    Course date: November 27th to November 29th 2013

Thank you

Pedro Fernandes
-- 
Pedro Fernandes
GTPB Coordinator
Instituto Gulbenkian de Ciência
Apartado 14
2781-901 OEIRAS
PORTUGAL
Tel +351 21 4407912
http://gtpb.igc.gulbenkian.pt

CSDM13 training Course
Chromosome structure determination using modelling and Hi-C data

In the analysis of patterns and processes occurred during the  
evolution of our genome, the detection of evolutionary forces acting  
in protein coding genes has already proved its relevance in the  
context of human health and disease [1]&#8288;. The tools generally  
used in this field are based in the concepts and methods of  
evolutionary genomics, phylogenetic analysis, and bioinformatics on  
the complete genomes of different mammalian species [2]&#8288;. The  
main outcome from this kind of analysis is the classification of  
specific features of our genomes into categories,  according to the  
impact of these differences on changes to evolution.

In the context of epigenetics, the relation with disease has been  
extensively studied, at the level of DNA methylation, histone  
modification and even chromatin remodeling [3]&#8288;. Under this last  
category some work has been done, more specifically on chromatin  
structure, that is able to highlight structural variations directly  
linked to human disease [4,5]&#8288;. Overall it is now widely  
accepted that the complete elucidation of chromatin three-dimensional  
structure is the next frontier in epigenetic studies; and some of its  
possible applications to human health are promising, as markers for  
gene expression state [6]&#8288;, in the understanding of the cancer  
process 7&#8288;, in the maintenance of cellular memories or in the  
modulation of phenotypes [8]&#8288;.

However, in the context of epigenetics the relation between selective  
pressure and the potential impact of observing epigenetic variation,  
although it has been reported [9,10&#8288;], has not yet been modeled  
or measured. The chromatin interaction map, that somehow summarizes  
the epigenetic state of a given genomic region [11]&#8288;, stands as  
a outstanding candidate to study how evolution may shape our  
epigenomic landscape, and, at present, potentially the only candidate  
to offer significant clues about the real role of the non-genic 95% of  
our genomes.

The CSDM13 course content

In this course we aim to share our experience in analyzing and  
inferring the structure of chromatin (how it folds in  
three-dimensions) [12–15]&#8288;. Using available Hi-C data,course  
participants will be asked to find topologically associating  
domains10&#8288;, infer evolutionary conservation (or cell  
specificity), calculate the physical distances between a gene and its  
promoter, infer chromatin accessibility of specific regions, etc.

Some computational skills are recommended for this course. However,  
the tools presented in this course are designed to be used by non  
computer-scientists. We will provide a basic introduction to the linux  
operating system and the Python programming language, aiming at  
quickly creating a working environment where every participant is  
guaranteed to engage. With this, we will minimize the danger of  
leaving anyone behind because of  healthy differences in background  
literacy about computing.

1. Thomas, P. D. & Kejariwal, A. Coding single-nucleotide  
polymorphisms associated with complex vs. Mendelian disease:  
evolutionary evidence for differences in molecular effects. Proc.  
Natl. Acad. Sci. U. S. A. 101, 15398 (2004).
2. Sánchez, R. et al. Phylemon 2.0: a suite of web-tools for molecular  
evolution, phylogenetics, phylogenomics and hypotheses testing.  
Nucleic Acids Res. 39, W470–4 (2011).
3. Portela, A. & Esteller, M. Epigenetic modifications and human  
disease. Nat. Biotechnol. 28, 1057–68 (2010).
4. Vavouri, T. & Lehner, B. Chromatin organization in sperm may be the  
major functional consequence of base composition variation in the  
human genome. PLoS Genet. 7, e1002036 (2011).
5. Engreitz, J. M., Agarwala, V. & Mirny, L. a. Three-dimensional  
genome architecture influences partner selection for chromosomal  
translocations in human disease. PLoS One 7, e44196 (2012).
6. Crutchley, J. L., Wang, X. Q. D., Ferraiuolo, M. a & Dostie, J.  
Chromatin conformation signatures: ideal human disease biomarkers?  
Biomark. Med. 4, 611–29 (2010).
7. Göndör, A. Nuclear architecture and chromatin structure on the path  
to cancer. Semin. Cancer Biol. 23, 63–4 (2013).
8. Göndör, A. Dynamic chromatin loops bridge health and disease in the  
nuclear landscape. Semin. Cancer Biol. 23, 90–8 (2013).
9. Nagase, H. & Ghosh, S. Epigenetics: differential DNA methylation in  
mammalian somatic tissues. FEBS J. 275, 1617–23 (2008).
10. Dixon, J. R. et al. Topological domains in mammalian genomes  
identified by analysis of chromatin interactions. Nature 485, 376–80  
(2012).
11. Tanay, A. & Cavalli, G. Chromosomal domains: epigenetic contexts  
and functional implications of genomic compartmentalization. Curr.  
Opin. Genet. Dev. 23, 197–203 (2013).
12. Dekker, J., Marti-Renom, M. a & Mirny, L. a. Exploring the  
three-dimensional organization of genomes: interpreting chromatin  
interaction data. Nat. Rev. Genet. 14, 390–403 (2013).
13. Baù, D. et al. The three-dimensional folding of the &#945;-globin  
gene domain reveals formation of chromatin globules. Nat. Struct. Mol.  
Biol. 18, 107–14 (2011).
14. Umbarger, M. a et al. The three-dimensional architecture of a  
bacterial genome and its alteration by genetic perturbation. Mol. Cell  
44, 252–64 (2011).
15. Baù, D. & Marti-Renom, M. a. Structure determination of genomic  
domains by satisfaction of spatial restraints. Chromosome Res. 19,  
25–35 (2011).

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