Bioinformatique et biologie des systèmes du cancer

Publications de l’équipe

Année de publication : 2006

Nicolas Robine, Norio Uematsu, Franck Amiot, Xavier Gidrol, Emmanuel Barillot, Alain Nicolas, Valérie Borde (2006 Dec 26)

Genome-wide redistribution of meiotic double-strand breaks in Saccharomyces cerevisiae.

Molecular and cellular biology : 1868-80 En savoir plus
Résumé

Meiotic recombination is initiated by the formation of programmed DNA double-strand breaks (DSBs) catalyzed by the Spo11 protein. DSBs are not randomly distributed along chromosomes. To better understand factors that control the distribution of DSBs in budding yeast, we have examined the genome-wide binding and cleavage properties of the Gal4 DNA binding domain (Gal4BD)-Spo11 fusion protein. We found that Gal4BD-Spo11 cleaves only a subset of its binding sites, indicating that the association of Spo11 with chromatin is not sufficient for DSB formation. In centromere-associated regions, the centromere itself prevents DSB cleavage by tethered Gal4BD-Spo11 since its displacement restores targeted DSB formation. In addition, we observed that new DSBs introduced by Gal4BD-Spo11 inhibit surrounding DSB formation over long distances (up to 60 kb), keeping constant the number of DSBs per chromosomal region. Together, these results demonstrate that the targeting of Spo11 to new chromosomal locations leads to both local stimulation and genome-wide redistribution of recombination initiation and that some chromosomal regions are inherently cold regardless of the presence of Spo11.

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Stéphane Liva, Philippe Hupé, Pierre Neuvial, Isabel Brito, Eric Viara, Philippe La Rosa, Emmanuel Barillot (2006 Jul 18)

CAPweb: a bioinformatics CGH array Analysis Platform.

Nucleic acids research : W477-81 En savoir plus
Résumé

Assessing variations in DNA copy number is crucial for understanding constitutional or somatic diseases, particularly cancers. The recently developed array-CGH (comparative genomic hybridization) technology allows this to be investigated at the genomic level. We report the availability of a web tool for analysing array-CGH data. CAPweb (CGH array Analysis Platform on the Web) is intended as a user-friendly tool enabling biologists to completely analyse CGH arrays from the raw data to the visualization and biological interpretation. The user typically performs the following bioinformatics steps of a CGH array project within CAPweb: the secure upload of the results of CGH array image analysis and of the array annotation (genomic position of the probes); first level analysis of each array, including automatic normalization of the data (for correcting experimental biases), breakpoint detection and status assignment (gain, loss or normal); validation or deletion of the analysis based on a summary report and quality criteria; visualization and biological analysis of the genomic profiles and results through a user-friendly interface. CAPweb is accessible at http://bioinfo.curie.fr/CAPweb.

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Philippe La Rosa, Eric Viara, Philippe Hupé, Gaëlle Pierron, Stéphane Liva, Pierre Neuvial, Isabel Brito, Séverine Lair, Nicolas Servant, Nicolas Robine, Elodie Manié, Caroline Brennetot, Isabelle Janoueix-Lerosey, Virginie Raynal, Nadège Gruel, Céline Rouveirol, Nicolas Stransky, Marc-Henri Stern, Olivier Delattre, Alain Aurias, François Radvanyi, Emmanuel Barillot (2006 Jul 6)

VAMP: visualization and analysis of array-CGH, transcriptome and other molecular profiles.

Bioinformatics (Oxford, England) : 2066-73 En savoir plus
Résumé

Microarray-based CGH (Comparative Genomic Hybridization), transcriptome arrays and other large-scale genomic technologies are now routinely used to generate a vast amount of genomic profiles. Exploratory analysis of this data is crucial in helping to understand the data and to help form biological hypotheses. This step requires visualization of the data in a meaningful way to visualize the results and to perform first level analyses.

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Pierre Neuvial, Philippe Hupé, Isabel Brito, Stéphane Liva, Elodie Manié, Caroline Brennetot, François Radvanyi, Alain Aurias, Emmanuel Barillot (2006 May 24)

Spatial normalization of array-CGH data.

BMC bioinformatics : 264 En savoir plus
Résumé

Array-based comparative genomic hybridization (array-CGH) is a recently developed technique for analyzing changes in DNA copy number. As in all microarray analyses, normalization is required to correct for experimental artifacts while preserving the true biological signal. We investigated various sources of systematic variation in array-CGH data and identified two distinct types of spatial effect of no biological relevance as the predominant experimental artifacts: continuous spatial gradients and local spatial bias. Local spatial bias affects a large proportion of arrays, and has not previously been considered in array-CGH experiments.

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Année de publication : 2005

Adil Elfilali, Séverine Lair, Catia Verbeke, Philippe La Rosa, François Radvanyi, Emmanuel Barillot (2005 Dec 31)

ITTACA: a new database for integrated tumor transcriptome array and clinical data analysis.

Nucleic acids research : D613-6 En savoir plus
Résumé

Transcriptome microarrays have become one of the tools of choice for investigating the genes involved in tumorigenesis and tumor progression, as well as finding new biomarkers and gene expression signatures for the diagnosis and prognosis of cancer. Here, we describe a new database for Integrated Tumor Transcriptome Array and Clinical data Analysis (ITTACA). ITTACA centralizes public datasets containing both gene expression and clinical data. ITTACA currently focuses on the types of cancer that are of particular interest to research teams at Institut Curie: breast carcinoma, bladder carcinoma and uveal melanoma. A web interface allows users to carry out different class comparison analyses, including the comparison of expression distribution profiles, tests for differential expression and patient survival analyses. ITTACA is complementary to other databases, such as GEO and SMD, because it offers a better integration of clinical data and different functionalities. It also offers more options for class comparison analyses when compared with similar projects such as Oncomine. For example, users can define their own patient groups according to clinical data or gene expression levels. This added flexibility and the user-friendly web interface makes ITTACA especially useful for comparing personal results with the results in the existing literature. ITTACA is accessible online at http://bioinfo.curie.fr/ittaca.

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Eugene Novikov, Emmanuel Barillot (2005 Dec 24)

A robust algorithm for ratio estimation in two-color microarray experiments.

Journal of bioinformatics and computational biology : 1411-28 En savoir plus
Résumé

The reliability of the algorithms for ratio estimation in two-color microarray image analysis is very important, as these ratios build up the primary source of information for the subsequent analytical procedures (normalization, clustering, classification, etc). Although various algorithms already exist, there is still a need to develop procedures having higher levels of accuracy and robustness. We present a statistical procedure for the detection and removal of aberrant pixels in two-color microarray images. It is based on a linear regression approach, assuming reasonably high level of correlation between the two color channels. This procedure ensures more robust ratio estimation for the spots in both linear regression and traditional segmentation algorithms. The developed algorithms have been evaluated using simulated artificial images and experimental images of different designs. A demonstration version of the software can be downloaded from http://bioinfo.curie.fr/projects/maia/.

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Eugene Novikov, Emmanuel Barillot (2005 Dec 13)

An algorithm for automatic evaluation of the spot quality in two-color DNA microarray experiments.

BMC bioinformatics : 293 En savoir plus
Résumé

Although DNA microarray technologies are very powerful for the simultaneous quantitative characterization of thousands of genes, the quality of the obtained experimental data is often far from ideal. The measured microarrays images represent a regular collection of spots, and the intensity of light at each spot is proportional to the DNA copy number or to the expression level of the gene whose DNA clone is spotted. Spot quality control is an essential part of microarray image analysis, which must be carried out at the level of individual spot identification. The problem is difficult to formalize due to the diversity of instrumental and biological factors that can influence the result.

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Isabelle Janoueix-Lerosey, Philippe Hupé, Zofia Maciorowski, Philippe La Rosa, Gudrun Schleiermacher, Gaëlle Pierron, Stéphane Liva, Emmanuel Barillot, Olivier Delattre (2005 Nov 19)

Preferential occurrence of chromosome breakpoints within early replicating regions in neuroblastoma.

Cell cycle (Georgetown, Tex.) : 1842-6 En savoir plus
Résumé

Neuroblastoma (NB) is a frequent paediatric extra cranial solid tumor characterized by the occurrence of unbalanced chromosome translocations, frequently, but not exclusively, involving chromosomes 1 and 17. We have used a 1 Mb resolution BAC array to further refine the mapping of breakpoints in NB cell lines. Replication timing profiles were evaluated in 7 NB cell lines, using DNAs from G1 and S phases flow sorted nuclei hybridised on the same array. Strikingly, these replication timing profiles were highly similar between the different NB cell lines. Furthermore, a significant level of similarity was also observed between NB cell lines and lymphoblastoid cells. A segmentation analysis using the Adaptative Weights Smoothing procedure was performed to determine regions of coordinate replication. More than 50% of the breakpoints mapped to early replicating regions, which account for 23.7% of the total genome. The breakpoints frequency per 10(8) bases was therefore 10.84 for early replicating regions, whereas it was only 2.94 for late replicating regions, these difference being highly significant (p < 10(-4)). This strong association was also observed when chromosomes 1 and 17, the two most frequent translocation partners in NB were excluded from the statistical analysis. These results unambiguously establish a link between unbalanced translocations, whose most likely mechanism of occurrence relies on break-induced replication, and early replication of the genome.

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Année de publication : 2004

Philippe Hupé, Nicolas Stransky, Jean-Paul Thiery, François Radvanyi, Emmanuel Barillot (2004 Sep 24)

Analysis of array CGH data: from signal ratio to gain and loss of DNA regions.

Bioinformatics (Oxford, England) : 3413-22 En savoir plus
Résumé

Genomic DNA regions are frequently lost or gained during tumor progression. Array Comparative Genomic Hybridization (array CGH) technology makes it possible to assess these changes in DNA in cancers, by comparison with a normal reference. The identification of systematically deleted or amplified genomic regions in a set of tumors enables biologists to identify genes involved in cancer progression because tumor suppressor genes are thought to be located in lost genomic regions and oncogenes, in gained regions. Array CGH profiles should also improve the classification of tumors. The achievement of these goals requires a methodology for detecting the breakpoints delimiting altered regions in genomic patterns and assigning a status (normal, gained or lost) to each chromosomal region.

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