[BBC] [Gtpb] Clarification about the CSDM training course
Pedro Fernandes
pfern at igc.gulbenkian.pt
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]⁠. 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]⁠. 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]⁠. 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]⁠. 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]⁠, in the understanding of the cancer
process 7⁠, in the maintenance of cellular memories or in the
modulation of phenotypes [8]⁠.
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], has not yet been modeled
or measured. The chromatin interaction map, that somehow summarizes
the epigenetic state of a given genomic region [11]⁠, 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) [1215]⁠. Using available Hi-C data,course
participants will be asked to find topologically associating
domains10⁠, 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, W4704 (2011).
3. Portela, A. & Esteller, M. Epigenetic modifications and human
disease. Nat. Biotechnol. 28, 105768 (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, 61129 (2010).
7. Göndör, A. Nuclear architecture and chromatin structure on the path
to cancer. Semin. Cancer Biol. 23, 634 (2013).
8. Göndör, A. Dynamic chromatin loops bridge health and disease in the
nuclear landscape. Semin. Cancer Biol. 23, 908 (2013).
9. Nagase, H. & Ghosh, S. Epigenetics: differential DNA methylation in
mammalian somatic tissues. FEBS J. 275, 161723 (2008).
10. Dixon, J. R. et al. Topological domains in mammalian genomes
identified by analysis of chromatin interactions. Nature 485, 37680
(2012).
11. Tanay, A. & Cavalli, G. Chromosomal domains: epigenetic contexts
and functional implications of genomic compartmentalization. Curr.
Opin. Genet. Dev. 23, 197203 (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, 390403 (2013).
13. Baù, D. et al. The three-dimensional folding of the α-globin
gene domain reveals formation of chromatin globules. Nat. Struct. Mol.
Biol. 18, 10714 (2011).
14. Umbarger, M. a et al. The three-dimensional architecture of a
bacterial genome and its alteration by genetic perturbation. Mol. Cell
44, 25264 (2011).
15. Baù, D. & Marti-Renom, M. a. Structure determination of genomic
domains by satisfaction of spatial restraints. Chromosome Res. 19,
2535 (2011).
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