Matthieu Defrance

Matthieu Defrance
Université Libre de Bruxelles | ULB · Computer Science Department

PhD

About

52
Publications
18,304
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3,869
Citations
Additional affiliations
October 2016 - present
Université Libre de Bruxelles
Position
  • Professor (Associate)
May 2010 - September 2016
Université Libre de Bruxelles
Position
  • PostDoc Position

Publications

Publications (52)
Article
In this study, we evaluated the MethylationEPIC BeadChip (850k) technology for enhancer methylation analysis with respect to RRBS, both high-throughput technologies commonly used to screen large patient cohorts. We developed and applied a new approach to re-annotate the 850k data, which greatly improved the association of probes to enhancers and sh...
Preprint
Background Illumina Infinium DNA Methylation (5mC) profiling arrays are a popular technology for low-cost, high-throughput, genome-scale measurement of 5mC distribution, especially in cancer and other complex diseases. After the success of its HumanMethylation450 array (450k), Illumina released the MethylationEPIC array (850k) featuring, in additio...
Article
Full-text available
Genome-wide association studies (GWASs) identified hundreds of signals associated with type 2 diabetes (T2D). To gain insight into their underlying molecular mechanisms, we have created the translational human pancreatic islet genotype tissue-expression resource (TIGER), aggregating >500 human islet genomic datasets from five cohorts in the Horizon...
Article
Full-text available
Memory CD8+ T cells have the ability to provide lifelong immunity against pathogens. Although memory features generally arise after challenge with a foreign antigen, naïve CD8 single positive (SP) thymocytes may acquire phenotypic and functional characteristics of memory cells in response to cytokines such as interleukin-4. This process is associat...
Article
Full-text available
The Sahara silver ant Cataglyphis bombycina is one of the world’s most thermotolerant animals. Workers forage for heat-stricken arthropods during the hottest part of the day, when temperatures exceed 50 °C. However, the physiological adaptations needed to cope with such harsh conditions remain poorly studied in this desert species. Using transcript...
Article
Full-text available
Cytotoxic CD4 (CD4CTX) T cells are emerging as an important component of anti-viral and anti-tumor immunity but the molecular basis of their development remains poorly understood. In the context of human cytomegalovirus infection, a significant proportion of CD4 T cells displays cytotoxic functions. We observed that the transcriptional program of t...
Data
Phenotype and function of in vivo differentiated perforin +human CD4 T cells. Numerical data corresponding to the graphs of Figure 1 panels b, e, f and g.
Data
Differentiation of CD4CTX T cells within the Th1 lineage. Numerical data corresponding to the graphs of Figure 3 panels c, d and f.
Data
Lists of genes included in the 12 GeneSets obtained from CD4 versus CD8 T cell comparison (Figure 2) and naive CD4 T cell versus CMTh1 cell versus CD4CTX T cell comparison (Figure 4). Genes expressed at higher level by the first listed subset as compared to the subset indicated between brackets were identified using the min/max method. Genes are ra...
Data
Naive CD4 T cells differentiate into CD4CTX in Th1 culture conditions in vitro. Numerical data corresponding to the graphs of Figure 6 panels c, d and e.
Data
(a) Level of methylation at individual CpG sites in memory Th1 cell subsets in vivo. The level of methylation was measured by pyrosequencing in memory Th1 cell subsets of two to nine CMV-seropositive healthy adults. Data are median percentage ± interquartile range and were compared with the Mann-Withney non-parametric test. † CMTh1 versus naive CD4...
Data
Method to analyze the correlation between gene expression and DNA methylation. Gene Set Enrichment Analysis (GSEA) was used to analyze the enrichment of DNA methylation profiles in the GeneSets expressed by T cell subsets. Five Perl scripts were created to prepare the file required for GSEA.
Data
TF controlling the expression of perforin in CD4 T cells. Numerical data corresponding to the graphs of Figure 7 panels b, d, e and g.
Data
The transcriptional program of CD4CTX T cells is enriched in CD8 lineage genes without down regulation of ThPOK. Numerical data corresponding to the graphs of Figure 2 panels d and e. For Figure 2g, raw methylation data of all probes included in the heatmap, including location on the gene, are presented.
Data
Proportion of PRF1 mRNA +cells and co-expression with transcription factors in the Th1 lineage. Single-cell expression values for each indicated genes (column) and each cell (lines).
Data
Transcriptional program underlying the expression of perforin in Th1 cells. Raw methylation data of all the probes included in the heatmap of Figure 5 panels e and f, including location on the gene.
Article
Full-text available
Background: The tumor immune response is increasingly associated with better clinical outcomes in breast and other cancers. However, the evaluation of tumor-infiltrating lymphocytes (TILs) relies on histopathological measurements with limited accuracy and reproducibility. Here, we profiled DNA methylation markers to identify a methylation of TIL (...
Article
Full-text available
The forkhead box P1 (FOXP1) transcription factor has been shown to regulate the generation and maintenance of quiescent naïve murine T cells. In humans, FOXP1 expression has been correlated with overall survival in patients with peripheral T-cell lymphoma (PTCL), although its regulatory role in T-cell function is currently unknown. We found that FO...
Article
Full-text available
Evidence is emerging that long noncoding RNAs (lncRNAs) may play a role in cancer development, but this role is not yet clear. We performed a genome-wide transcriptional survey to explore the lncRNA landscape across 995 breast tissue samples. We identified 215 lncRNAs whose genes are aberrantly expressed in breast tumors, as compared to normal samp...
Article
Full-text available
Hydroxymethylcytosine, well described in DNA, occurs also in RNA. Here, we show that hydroxymethylcytosine preferentially marks polyadenylated RNAs and is deposited by Tet in Drosophila. We map the transcriptome-wide hydroxymethylation landscape, revealing hydroxymethylcytosine in the transcripts of many genes, notably in coding sequences, and iden...
Article
Full-text available
The TET enzymes convert methylcytosine to the newly discovered base hydroxymethylcytosine. While recent reports suggest that TETs may play a role in response to oxidative stress, this role remains uncertain, and results lack in vivo models. Here we show a global decrease of hydroxymethylcytosine in cells treated with buthionine sulfoximine, and in...
Article
Sox9 is a transcription factor expressed in most solid tumors. However, the molecular mechanisms underlying Sox9 function during tumorigenesis remain unclear. Here, using a genetic mouse model of basal cell carcinoma (BCC), the most frequent cancer in humans, we show that Sox9 is expressed from the earliest step of tumor formation in a Wnt/β-cateni...
Article
Full-text available
RSAT (Regulatory Sequence Analysis Tools) is a modular software suite for the analysis of cis-regulatory elements in genome sequences. Its main applications are (i) motif discovery, appropriate to genome-wide data sets like ChIP-seq, (ii) transcription factor binding motif analysis (quality assessment, comparisons and clustering), (iii) comparative...
Article
Full-text available
The discovery of cytosine hydroxymethylation (5hmC) as a mechanism that potentially controls DNA methylation changes typical of neoplasia prompted us to investigate its behaviour in colon cancer. 5hmC is globally reduced in proliferating cells such as colon tumours and the gut crypt progenitors, from which tumours can arise. Here, we show that colo...
Article
Full-text available
DNA methylation and histone modifications are key epigenetic regulators of gene expression, and tight connections are known between the two. DNA methyltransferases are upregulated in several tumors and aberrant DNA methylation profiles are a cancer hallmark. On the other hand, histone demethylases are upregulated in cancer cells. Previous work on E...
Article
Full-text available
DNA methylation is a central epigenetic modification that is established by de novo DNA methyltransferases. The mechanisms underlying the generation of genomic methylation patterns are still poorly understood. Using mass spectrometry and a phosphospecific Dnmt3a antibody, we demonstrate that CK2 phosphorylates endogenous Dnmt3a at two key residues...
Article
Full-text available
j.celrep.2014.06.048 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). SUMMARY DNA methylation is a central epigenetic modifi-cation that is established by de novo DNA methyl-transferases. The mechanisms underlying the gene-ration of genomic methylation patterns are still poorly unders...
Article
Full-text available
In a recent intervention study, the daily supplementation with 200 mg monomeric and oligomeric flavanols (MOF) from grape seeds for 8 weeks revealed a vascular health benefit in male smokers. The objective of the present study was to determine the impact of MOF consumption on the gene expression profile of leukocytes and to assess changes in DNA me...
Article
Full-text available
Infinium HumanMethylation450 beadarray is a popular technology to explore DNA methylomes in health and disease, and there is a current explosion in the use of this technique. Despite experience acquired from gene expression microarrays, analyzing Infinium Methylation arrays appeared more complex than initially thought and several difficulties have...
Article
ChIP-seq is increasingly used to characterize transcription factor binding and chromatin marks at a genomic scale. Various tools are now available to extract binding motifs from peak data sets. However, most approaches are only available as command-line programs, or via a website but with size restrictions. We present peak-motifs, a computational p...
Article
Full-text available
TET proteins convert 5-methylcytosine to 5-hydroxymethylcytosine, an emerging dynamic epigenetic state of DNA that can influence transcription. Evidence has linked TET1 function to epigenetic repression complexes, yet mechanistic information, especially for the TET2 and TET3 proteins, remains limited. Here, we show a direct interaction of TET2 and...
Article
s: Thirty-Fifth Annual CTRC‐AACR San Antonio Breast Cancer Symposium‐‐ Dec 4‐8, 2012; San Antonio, TX Background: A significant proportion of breast cancer (BC) patients (pts) develop multiple synchronous unilateral breast tumors, also referred to as multifocal BC (MBC), which represent a diagnostic and therapeutic challenge. Here, we aimed first...
Article
Full-text available
This protocol explains how to use the online integrated pipeline 'peak-motifs' (http://rsat.ulb.ac.be/rsat/) to predict motifs and binding sites in full-size peak sets obtained by chromatin immunoprecipitation-sequencing (ChIP-seq) or related technologies. The workflow combines four time- and memory-efficient motif discovery algorithms to extract s...
Article
Full-text available
http://rsat.ulb.ac.be/rsat/ ChIP-seq has become a method of choice to study binding preferences of transcription factors, and localization of epigenetic regulatory marks at a genomic scale. There is a crucial need for specialized software tools to make sense of these data. While various programs have been developed to perform read mapping and peak...
Article
Full-text available
In addition to genetic predisposition, environmental and lifestyle factors contribute to the pathogenesis of type 2 diabetes (T2D). Epigenetic changes may provide the link for translating environmental exposures into pathological mechanisms. In this study, we performed the first comprehensive DNA methylation profiling in pancreatic islets from T2D...
Article
Full-text available
ChIP-seq is increasingly used to characterize transcription factor binding and chromatin marks at a genomic scale. Various tools are now available to extract binding motifs from peak data sets. However, most approaches are only available as command-line programs, or via a website but with size restrictions. We present peak-motifs, a computational p...
Article
Full-text available
Breast cancer is a molecularly, biologically and clinically heterogeneous group of disorders. Understanding this diversity is essential to improving diagnosis and optimizing treatment. Both genetic and acquired epigenetic abnormalities participate in cancer, but the involvement of the epigenome in breast cancer and its contribution to the complexit...
Article
Full-text available
Studies of DNA methylomes hold enormous promise for biomedicine but are hampered by the technological challenges of analyzing many samples cost-effectively. Recently, a major extension of the previous Infinium HumanMethylation27 BeadChip® (Illumina, Inc. CA, USA), called Infinium HumanMethylation450 (Infinium Methylation 450K; Illumina, Inc. CA, US...
Article
Background: Understanding the diversity of breast cancer is essential to improving diagnosis and optimising treatment. Both genetic and acquired epigenetic abnormalities participate in cancer, but information is scant on the involvement of the epigenome in breast cancer and its contribution to the complexity of the disease. Our goal was to explore...
Article
Full-text available
RSAT (Regulatory Sequence Analysis Tools) comprises a wide collection of modular tools for the detection of cis-regulatory elements in genome sequences. Thirteen new programs have been added to the 30 described in the 2008 NAR Web Software Issue, including an automated sequence retrieval from EnsEMBL (retrieve-ensembl-seq), two novel motif discover...
Article
Discovering cis-regulatory elements in genome sequence remains a challenging issue. Several methods rely on the optimization of some target scoring function. The information content (IC) or relative entropy of the motif has proven to be a good estimator of transcription factor DNA binding affinity. However, these information-based metrics are usual...
Article
Full-text available
The regulatory sequence analysis tools (RSAT, http://rsat.ulb.ac.be/rsat/) is a software suite that integrates a wide collection of modular tools for the detection of cis-regulatory elements in genome sequences. The suite includes programs for sequence retrieval, pattern discovery, phylogenetic footprint detection, pattern matching, genome scanning...
Article
Full-text available
This protocol shows how to detect putative cis-regulatory elements and regions enriched in such elements with the regulatory sequence analysis tools (RSAT) web server (http://rsat.ulb.ac.be/rsat/). The approach applies to known transcription factors, whose binding specificity is represented by position-specific scoring matrices, using the program m...
Article
Full-text available
This protocol explains how to discover functional signals in genomic sequences by detecting over- or under-represented oligonucleotides (words) or spaced pairs thereof (dyads) with the Regulatory Sequence Analysis Tools (http://rsat.ulb.ac.be/rsat/). Two typical applications are presented: (i) predicting transcription factor-binding motifs in promo...
Article
Full-text available
Identifying cis-regulatory elements is crucial to understanding gene expression, which highlights the importance of the computational detection of overrepresented transcription factor binding sites (TFBSs) in coexpressed or coregulated genes. However, this is a challenging problem, especially when considering higher eukaryotic organisms. We have de...

Projects

Projects (2)
Project
This project aims to investigate how desert ants have evolved their extreme degree of thermophily through transcriptomic and functional analyses.