CGM - Department Dynamics & Stability of Genomes
More about the team "Genome analysis"
Group leader: Claude THERMES
Last update: 01-Dec-2009
Current research
The information content of genomic sequences not only results from constraints associated to genetic information (transcription signals, protein coding regions, etc.) but also, among others, from constraints associated to cellular mechanisms like replication or chromatin dynamics. We study how these latter mechanisms affect the writing of genome sequences, in relation with recent high throughput data concerning gene expression, replication timing or chromatin fiber structure. These thematics involve various methodologies related to bioinformatics as well as to physics, and present multidisciplinary features that lead us to maintain constant collaborations with physicists (A. Arneodo, ENS, Lyon).
The study of genome compositional heterogeneity (GC content, strand asymmetries) let us to analyze on genome scale the links between replication, gene expression and gene organization. During evolution, strand asymmetries intrinsic to the mutation-repair processes can lead to nucleotide composition biases. The study of these biases along genome sequences allowed, in prokaryotes the identification of replication origins. However, in eukaryotes this approach was unsuccessful. The study of strand asymmetries in genomes of higher eukaryotes let us us to tackle the unsolved problem of the identification of replication origins. This methodology allows us to examine, at genome scale, the possible relationship between replication, gene expression and gene organization. We collaborate with biologists in order to validate and to study the predicted replication origins (molecular combing, micorarrays, in situ studies) (http://replicor.cgm.cnrs-gif.fr/index.html) (collaboration with O. Hyrien, ENS Paris ; F. Mongelard, ENS, Lyon).
We study long-range correlations in genome sequences between nucleotides as well as between DNA sequence motifs presenting particular bending properties, in order to examine the role of these correlations in chromatin structure. The results show that the correlations observed in the 1-200 bp scale range are a signature of chromatin organization in eukaryotes and contribute to the nucleosome formation and dynamics. At larger scales (> 200 bp) we observe correlations in the three kingdoms, eukaryotes, eubacteria and archaebacteria. We propose that long-range correlations in this scale range (up to thousands base pairs) are related to universal properties of chromatin organization. This type of information would superimpose to genetic information (protein coding regions, control of gene expression) and would present scale invariant properties that we analyze with the "mathematic microscope" of the wavelet transform methodology.
Another of our research interests concerns computer identification and analysis of non protein coding RNA genes (npcRNAs). Recent data show that among this class of genes, which would constitute more than half of human transcripts, an increasing number play important regulatory roles (RNA interference, imprinting, chromatin modification). We are partners of a European project (RIBOREG, http://www.isv.cnrs-gif.fr/mc/riboreg/index.php) dedicated to the detection of npsRNAs in human, mouse and Arabidopsis, and to the analysis of their roles in differentiation and disease. We use ESTs and cDNAs to identify candidate genes presenting sequence or structural features conserved between species. These genes are experimentally analyzed to explore their functions, their mechanisms of action and their impact on differentiation and pathologies (collaboration with M. Crespi, ISV, Gif-sur-Yvette).
Collaborations
Alain Arneodo (ENS, Lyon)
Martin Crespi (ISV, Gif-sur-Yvette)
Richard Lavery (IBPC, Paris)
Olivier Hyrien (ENS, Paris)
Fabien Mongelard (ENS, Lyon)
Sophie Schbath (MIG, Jouy-en-Josas)
Thèses
Maxime Huvet
"Rôle de la réplication dans l'évolution et l'organisation du génome humain" (2008) Thèse de l'Université Denis Diderot, Paris VII
Marie Touchon
"Asymétries compositionnelles chez les eucaryotes" (2005) Thèse de l’Université Paris VII.
Nicolas Charlet-Berguerand
"Etude de la régulation de l'épissage alternatif des pré-messagers RET, GFRa1, cTNT et ClC1" (2003) Thèse de l'Université Paris VII.
Hervé le Hir
"Etude de l'epissage alternatif des ARN pré-messagers du gène RET et du gène de la tyrosine hydroxylase dans les phéochromocytomes" (1998) Thèse de l'Université Paris VII.
Students
- Philippe Alexandre, Master2 (2008)
- Pauline Pardieu, Master Student (2007)
- Emna Marrakchi, Master Student (2005-2007)
- Samuel Plessis-Fraissard EPITA (2003)
- Solen Deudé DESS (2002-2003)
- Pierre Kubiak (2002)
- Elodie Guillaume DESS (2001-2002)
- Ludovic Cottret (2000-2001)
Engineers
- Lauranne Duquenne (2007-2008)
- Antoine Lucas (2006)
- Vincent Lefort CDD (2003)
- Ludovic Cottret (2002)
Publications
2009
- Vaillant, C., Palmeira, L., Chevereau, G., Audit, B., d'Aubenton-Carafa, Y., Thermes, C. and Arneodo, A. (2009) A novel strategy of transcription regulation by intra-genic nucleosome ordering.
Genome Res, Epub ahead of print.
- Chevereau, G., Palmeira, L., Thermes, C., Arneodo, A. and Vaillant, C. (2009) Thermodynamics of nucleosome ordering by genomic confinement.
Phys Rev Letters, 103 (18) 188103.
- Audit, B., Zaghloul, L., Vaillant, C., Chevereau, G., d'Aubenton-Carafa, Y., Thermes, C. and Arneodo, A. (2009)
Open chromatin encoded in DNA sequence is the signature of 'master' replication origins in human cells.
Nucleic Acids Res, 37 (18) 6064-75.
- Guérin, A., d'Aubenton-Carafa, Y., Marrakchi, E., Da Silva, C., Wincker, P., Mazan, S., Rétaux, S. (2009) Neurodevelopment genes in lampreys reveal trends for forebrain evolution in craniates.
PLoS ONE, 4 (4) e5374.
- Neil, H. , Malabat, C., d’Aubenton-Carafa, Y., Xu, Z. Steinmetz, L.M. and Jacquier, A. (2009) Widespread bidirectional promoters are the major source of cryptic transcripts in yeast.
Nature, 457 (7232) 1038-42.
- Ben Amor, B., Wirth, S., Merchan, F., Laporte, P., d'Aubenton-Carafa, Y., Hirsch, J., Maizel, A., Mallory, A., Lucas, A., Deragon, J.-M., Vaucheret, H., Thermes, C. and Crespi, M. (2009) Novel long non-protein coding RNAs involved in Arabidopsis differentiation and stress responses.
Genome Res, 19 (1) 57-69.
2008
- Miele, V., Vaillant, C., d'Aubenton-Carafa, Y., Thermes, C. and Grange, T. (2008) DNA physical properties determine nucleosome occupancy from yeast to fly.
Nucleic Acids Res, 36 (11) 3746-56.
- Arneodo, A., Audit, B., Faivre-Moskalenko, C., Moukhtar, J., Vaillant, C., Argoul, F., d'Aubenton Carafa, Y. and Thermes, C. (2008) "From DNA sequence to chromatin organization: the fundamental role of genomic long-range correlations".
in Bulletin de l’Académie Royale de Belgique, Classe des Sciences, Académie Royale de Belgique, TomeXXVIII, n° 2049, 107p.
2007
Audit, B., Nicolay, S., Huvet, M., Touchon, M., d'Aubenton-Carafa, Y., Thermes, C. and Arneodo, A. (2007) DNA replication timing data corroborate in silico human replication origin predictions.
Physical Review Letters, 99 (24) 248102.
Huvet, M., Nicolay, S., Touchon, M., Audit, B., d'Aubenton-Carafa, Y., Arneodo, A. and Thermes, C. (2007) Human gene organization driven by the coordination of replication and transcription.
Genome Res, 17 (9) 1278-1285.
Nicolay, S., Brodie of Brodie, E.B., Touchon, M., Audit, B., d'Aubenton-Carafa, Y., Thermes, C. and Arneodo, A. (2007) Bifractality of human DNA strand-asymmetry profiles results from transcription.
Physical Review E, 75 (3-1) 032902.
Arneodo, A., d'Aubenton Carafa, Y., Audit, B., Brodie of Brodie, E.B., Nicolay, S., Saint-Jean, P., Thermes, C., Touchon, M. and Vaillant, C. (2007)
DNA in chromatin: from genome wide sequence analysis to the modeling of replication in mammals
Adv Chem Phys 135 203-225
Arneodo, A., Audit, B., Brodie of Brodie, E.-B., Nicolay, S., St Jean, P., d'Aubenton-Carafa, Y., Thermes, C. and Touchon, M. (2007) DNA in Chromatin: from genome-wide sequence analysis to the modeling of replication in mammals.
in Special Volume in Memory of Ilya Prigogine: Advances in Chemical Physics 135, S.-A. Rice (Ed.), John Wiley & Sons,
Arneodo, A., Audit, B., Brodie of Brodie, E.-B., Nicolay, S., Touchon, M., d'Aubenton Carafa, Y., Huvet, M.. and Thermes, C. (2007) Fractals and Wavelets: what can we learn on transcription and replication from wavelet-based multifractal analysis of DNA sequences?
in Encyclopedia of Complexity and System Science sous presse.
Arneodo, A., Audit, B., Faivre-Moskalenko, C., Moukhtar, J., Vaillant, C., Argoul, F., d'Aubenton Carafa, Y. and Thermes, C. (2007) From DNA sequence to chromatin organization: the fundamental role of genomic long-range correlations.
in Bulletin de l’Académie Royale de Belgique, Classe des Sciences sous presse.
Arneodo, A., Vaillant, C., Audit, B., d'Aubenton Carafa, Y. and Thermes, C. (2007) What Can We Learn from the Analysis of Scale Invariance and Long-range Correlation Properties of DNA Sequences Using Wavelet Techniques?
in Modern Mathematical Models, Methods and Algorithms for Real World Systems, A.-H. Siddiqi, I.-S. Duff and O. Christensen (Ed.), Anamaya, New Delhi. sous presse
2006
Arneodo, A., d’Aubenton-Carafa, Y., Audit, B., Brodie of Brodie, E. B., Nicolay, S., Saint-Jean, P., Thermes, C., Touchon, M. and Vaillant, C. (2006)
Large-scale analysis of the human genome : from DNA sequence analysis to the modelling of replication in higher eucaryotes.
14 th EUSIPCO. Florence, Italy.
Hirsch, J., Lefort, V., Vankersschaver, M., Boualem, A., Thermes, C., d'Aubenton Carafa, Y. and Crespi, M. (2006)
Characterization of 43 non-protein coding mRNA genes in Arabidopsis reveals the miR162a primary transcript.
Plant Phys., 140 1192-1204.
Vaillant, C., Audit, B., Thermes, C. and Arneodo, A. (2006)
Formation and positioning of nucleosomes: effect of sequence dependent long-range correlated structural disorder.
Eur. Phys. J. E ,19, 263-277.
Guédon, Y., d'Aubenton Carafa, Y. and Thermes, C. (2006)
Constructing lumped processes from Markov chains with an application to DNA sequence analysis.
J. Appl. Math. , 52 , 343-372.
2005
Touchon, M., Nicolay, S., Audit, B., Brodie of Brodie, E.B., d'Aubenton-Carafa, Y., Arneodo, A. and Thermes, C. (2005)
Replication-associated strand asymmetries in mammalian genomes: Toward detection of replication origins.
Proc. Natl. Acad. Sci. USA , 102, 9836-9841.
Brodie of Brodie, E.B., Nicolay, S., Touchon, M., Audit, B., d'Aubenton-Carafa, Y., Thermes, C. and Arneodo, A. (2005)
From DNA Sequence Analysis to Modeling Replication in the Human Genome.
Phys. Rev. Lett. , 94, 248103.
2004
Touchon, M., Arneodo, A., d'Aubenton-Carafa, Y. & Thermes, C. (2004)
Transcription-coupled and splicing-coupled strand asymmetries in eukaryotic genomes.
Nucleic Acids Res. 32: 4969-4978.
Nicolay S, Argoul, F, Touchon, M, d'Aubenton-Carafa, Y, Thermes C & Arneodo A (2004)
Low frequency rhythms in human DNA sequences: a key to the organization of gene location and orientation?
Phys. Rev. Lett. 93: 108101.
Nicolay S, Brodie of Brodie EB, Touchon M, d'Aubenton Carafa Y, Thermes C & Arneodo A (2004)
From scale invariance to deterministic chaos in DNA sequences: towards a deterministic description of gene organization in the human genome.
Physica A 342: 270-280.
Audit, B., Vaillant, C., Arneodo, A., d'Aubenton-Carafa, Y. and Thermes, C. (2004)
Wavelet analysis of DNA bending profiles reveals structural constraints on the evolution of genomic sequences.
J. Biol. Phys. 30: 33-81.
Charlet-Berguerand, N., Le Hir, H., Incoronato, M., Di Porzio, U., Yu, Y., Jing, S., De Franciscis, V. and Thermes, C (2004). Expression of GFRalpha1 receptor splicing variants with different biochemical properties is modulated during kidney development.
Cell Signal 16: 1425-1434.
2003
Touchon, M., Nicolay, S., Arneodo, A., d'Aubenton-Carafa, Y. & Thermes, C. (2003)
Transcription-coupled TA and GC strand asymmetries in the human genome.
FEBS Lett. 555: 579-582.
Vaillant, C., Audit, B., Thermes, C. and Arneodo, A. (2003)
Influence of the sequence on elastic properties of long DNA chains.
Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 67: 032901.
Arneodo, A., Audit, B., Vaillant, C., d'Aubenton-Carafa, Y. and Thermes, C. (2003)
Extracting structural and dynamical informations from wavelet-based analysis of DNA sequences.
In J-P. Gazeau, R. K., J-P. Antoine, S. Metens and J-Y. Thibon (ed.), GROUP 24: Physical and Mathematical Aspects of Symmetries. IOPP Publishing, Bristol.
Crespi, M., Campalans, A., Thermes, C. & Kondorosi, A. (2003)
New Perspectives on Noncoding or Short ORF-Encoding RNAs.
In Plant Noncoding RNAs: Molecular Biology and Molecular Medicine, pp. 193-202.
Raux E., Leech HK., Beck ., Schubert HL., Santander PJ., Roessner CA., Scott A.I., Martens J.H., Jahn D., Thermes C et al. (2003).
Identification and functional analysis of enzymes required for precorrin-2 dehydrogenation and metal ion insertion in the biosynthesis of sirohaem and cobalamin in Bacillus megaterium.
Biochem. J. 370: 505-516.
2002
Audit, B., Vaillant, C., Arneodo, A., d'Aubenton-Carafa, Y. and Thermes, C. (2002)
Long-range correlations between DNA bending sites: relation to the structure and dynamics of nucleosomes.
J. Mol. Biol. 316: 903-918.
Vermat, T., Vandenbrouck, Y., Viari, A. and d'Aubenton Carafa, Y. (2002)
Prediction, distribution and evolution of intrinsic transcription terminators in bacterial genomes.
In Nicolas J and Thermes C (eds.), JOBIM Proceedings, pp. 137-142.
Le Hir, H., Charlet-Berguerand, N., de Franciscis, V. & Thermes, C. (2002)
5'-End RET splicing: absence of variants in normal tissues and intron retention in pheochromocytomas.
Oncology 63: 84-91.
Previous publications (1998-2001)
Audit, B., Thermes, C., d'Aubenton-Carafa, Y., Vaillant, C., Muzy, J.F. and Arneodo, A. (2001) Long-range corrélations in genomic DNA : a signature of nucleosomal DNA. Phys. Rev. Let. 86, 2471-2474.
Le Hir, H., Charlet-Berguerand, N., Gimenez-Roqueplo, A.P., Mannelli, M., Plouin, P.F., de Franciscis, V. and Thermes, C. (2000). Relative expression of the RET9 and RET51 isoforms in human pheochromocytomas. Oncology 58, 311-318.
Le Hir, H., Colucci-D'Amato, GL., Charlet-Berguerand, N., Plouin, PF., Bertagna, X., de Franciscis, V. and Thermes, C. (2000). High levels of tyrosine phosphorylated proto-Ret in sporadic pheochromocytomas. Canc. Res. 1365-1370.
Menaa, F., Charlet, N. and Thermes, C. (2000) Etude de l'épissage alternatif des transcrits du co-récepteur du GDNF. L'année Gérontologique 14, 121-123.
Vignal, L., Lisacek, F., Quinqueton, J., d'Aubenton-Carafa, Y. and Thermes, C. (1999). A multi agent system simulating splice site recogntion. Comp. Chem. 23, 219-231.
Charrier, B., Foucher, F., Kondorosi, E., d'Aubenton-Carafa, Y., Thermes, C., Kondorosi, A. and Ratet, P. (1999). Bigfoot: a new family of MITE elements characterized from the Medicago genius. The Plant J. 18, 431-441.
Arneodo, A., d'Aubenton-Carafa, Y., Audit, B., Bacry, E., Muzy, J.F., and Thermes, C. (1998) What can we learn with wavelets about DNA sequences ? Physica A 249, 439-448.
Arneodo, A., d'Aubenton-Carafa, Y., Audit, B., Bacry, E., Muzy, J.F., and Thermes, C. (1998). Nucleotide composition effects on the long-range correlations in human genes. Eur. Phys. J. B 1, 259-263.
