Dr Touati Benoukraf’s research focus is the role of non-coding segments of the genome in order to identify novel regulatory elements such as enhancers or silencers with the aim of understanding their function in human physiology and pathology. More specifically, he uses epigenetic marks and transcription factor binding site datasets derived from high-throughput sequencing technologies to annotate and predict the function of these uncharacterized loci. This information allows the investigation of genomic and epigenomic aberrations in cancers beyond genes and the delineation of novel disease-related signaling pathways. Dr Benoukraf has developed several open source software applications to manage large epigenetic datasets and one of his contributions in this field was to describe the association between histone post-translational modifications and enhancer activities which enables the prediction of enhancer states from in vivo epigenetic data.
Deep sequencing is enabling new insights into mechanisms of gene regulation including the involvement of intergenic elements. 97% of human DNA is non-coding, and significant portions of this comprise cis-regulatory elements such as enhancers, silencers or insulators which are involved in the spacial-temporal gene regulation. Recent whole genome sequencing as well genome-wide association studies have shown that alterations of these non-coding elements can modify specific signaling pathways and consequently lead to disease. However, in contrast to coding genes, there is no comprehensive record of such regions, making the investigation of regulatory elements alterations challenging. We are developing informatics solutions for integrating in-house and published high-throughput sequencing data (genome and epigenome) in order to decipher and annotate these unexplored segments of DNA. This will allow us to build a framework for the investigation of cancers genomic aberrations moving forward from coding genes, and identify non-coding alterations involved in tumorigenesis.
- Suh HC*, Benoukraf T*, Shyamsunder P*, Yin T*, Cao Q, Said J, Lee S, Lim R, Yang H, Salotti J, Johnson PF, Madan V, Koeffler HP. LPS independent activation of the pro-inflammatory receptor Trem1 by C/EBPε in granulocytes. Sci Rep. 2017 Apr 25;7:46440.
- Tirado-Magallanes R, Rebbani K, Lim R, Pradhan S, Benoukraf T. Whole genome DNA methylation: beyond genes silencing. Oncotarget. 2017 Jan 17;8(3):5629-5637.
- Adusumalli S, Mohd Omar MF, Soong R, Benoukraf T. Methodological aspects of whole-genome bisulfite sequencing analysis. Brief Bioinform. 2015 May;16(3):369-79.
- Bard-Chapeau EA, Nguyen AT, Rust AG, Sayadi A, Lee P, Chua BQ,New LS, de Jong J, Ward JM, Chin CK, Chew V, Toh HC, Abastado JP, Benoukraf T, Soong R, Bard FA, Dupuy AJ, Johnson RL, Radda GK, Chan EC, Wessels LF, Adams DJ, Jenkins NA, Copeland NG.Transposon mutagenesis identifies genes driving hepatocellular carcinoma in a chronic hepatitis B mouse model. Nature Genetics. 2014 Jan;4(1):24-32.
- Di Ruscio A, Ebralidze AK, Benoukraf T, Amabile G, Goff LA, Terragni J, Figueroa ME, De Figueiredo Pontes LL, Alberich-Jorda M, Zhang P, Wu M, D’Alo F,Melnick A, Leone G, Ebralidze KK, Pradhan S, Rinn JL, Tenen DG. DNMT1-interacting RNAs block gene-specific DNA methylation.Nature. 2013 Nov 21;503(7476):371-6.
- Benoukraf T†, Wongphayak S, Hadi LH, Wu M, Soong R†. GBSA: a comprehensive software for analysing whole genome bisulfite sequencing data.Nucleic Acids Res. 2013 Feb 1;41(4):e55.
- Pekowska A*, Benoukraf T*, Zacarias-Cabeza J*, Belhocine M, Koch F, Holota H, Imbert J, Andrau JC, Ferrier P, Spicuglia S.H3K4 tri-methylation provides an epigenetic signature of active enhancers. EMBO J. 2011 Aug 16;30(20):4198-210.
- Pekowska A, Benoukraf T, Ferrier P, Spicuglia S. A unique H3K4me2 profile marks tissue-specific gene regulation.Genome Res. 2010 Nov;20(11):1493-502.
- Bonnet M, Huang F, Benoukraf T, Cabaud O, Verthuy C, Boucher A, Jaeger S, Ferrier P, Spicuglia S. Duality of enhancer functioning mode revealed in a reduced TCR beta gene enhancer knockin mouse model.J Immunol. 2009 Dec 15;183(12):7939-48.
- Benoukraf T, Cauchy P, Fenouil R, Jeanniard A, Koch F, Jaeger S, Thieffry D, Imbert J, Andrau JC, Spicuglia S, Ferrier P.CoCAS: a ChIP-on-chip analysis suite.Bioinformatics. 2009 Apr 1;25(7):954-5.
†: Corresponding authors
*: Joined first authors
|Affiliations||Research Assistant Professor, Cancer Science Institute of Singapore, NUS|
|Institute||Degree (if applicable)||Year(s)|
|Immunology Center of Marseille-Luminy (CIML), National Center for Scientific Research (CNRS), University of Aix-Marseille II, France||Ph.D.||2010|
|Department of Biology, University of Aix-Marseille II, France||Master||2006|
|Department of Computer Science, University of Aix-Marseille II, France||BSc||2004|
|•||Head, Computational Core, Cancer Science Institute of Singapore, National University of Singapore||2014 – Present|
|•||Research Assistant Professor, Cancer Science Institute of Singapore, National University of Singapore||2012 – Present|
|•||Research Fellow, Cancer Science Institute of Singapore, National University of Singapore||2010 – 2012|
|•||Lecturer, Department of Mathematics, University of Aix-Marseille II, France||2008 – 2010|
|•||Co-founder & co-chairman, startup company Comline, Marseille, France||2002 – 2009|
Epigenetic regulation in solid tumors
Decipher the causes of DNA methylation aberrations in tumor cells
PhD Student (TLL)
Gene regulation networks based on sequencing methods.
LOH Wan Yi (Hayley)
IT support (Computational Core Facility) and Software design
Interplay between pioneer transcription factor and DNA methylation
THAM Cheng Yong
Algorithms for long reads sequencing technologies
Roberto TIRADO MAGALLANES
DNA methylation meta-analysis.