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Gilles Thomas Bioinformatics Platform
Main activities
Since 2009, the platform has been actively involved in cancer genomics research programs within the International Cancer Genome Consortium (ICGC[lien http]) that undertook the systematic study of more than 25,000 cancer genomes, from 50 different types, at the genomic, epigenomic and transcriptomic levels. In this context, the platform participated to 3 INCa/INSERM funded programs: HER2-amplified breast cancer, prostate cancer and gynecological carcinosarcoma. It also provided some help and guidance to other French ICGC programs such as retinoblastoma.
During the past ten years, the platform has developped several projects at the national or regional (CRCL) levels and gained a strong expertise in the analysis of transcriptomics (bulk and single cell) and epigenetics data.
The platform also has an expertise in the field of genome-wide associations studies (GWAS) and is in charge of the statistical analyses of two major national Breast Cancer cohorts: CANTO (UniCancer and Labex GenMed partnership) and PHARE/SIGNAL (INCa funded program).
In addition, the platform is leading the bioinformatics developments and analyses in several precision medicine initiatives. It participates, since 2013, to the Lyric ProfiLER collaborative effort with the CLB clinical department to explore the therapeutic impact of molecular profiling (gene panel sequencing) in routine setting for patients.
More recently, in 2017, it was committed to the French national healthcare Plan France Médecine Génomique 2025. The platform is coordinating the bioinformatics operations (with the CHUGA in Grenoble) for the AURAGEN national sequencing platform, generating thousands of Whole Genome Sequences (WGS) per year in a clinical setting for cancer and rare diseases.
Missions
The general mission of the bioinformatics facility is to empower biomedical and research teams working in the field of cancer to fully exploit the data generated through large scale genomic projects. In accordance with this mission, the platform provides:
- collaborative support in bioinformatics and biostatistics to researchers and clinicians
- collaborative support to other CLB/CRCL technological platforms
- research and development of new methods, algorithms or tools
- access and support to high performance computing
- state-of-the-art automatic pipelines for data processing and analysis
- data management and integration with structured databases
- mentoring of young bioinformaticians from collaborating research teams
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The Gilles Thomas Bioinformatics Platform is operated by the Synergie Lyon Cancer Foundation. If you have any request, please send an email to contact-pgt@lyon.unicancer.fr
Team members
Presentation
The “Gilles Thomas” Bioinformatics Facility, located at the Centre Léon Bérard (CLB), was initiated in 2009 by Pr. Gilles Thomas to foster the exploitation of massive amounts of sequencing data in cancer genomics. The team is composed of 11 bioinformaticians and biostatisticians working under the scientific supervision of Alain Viari (Inria). It provides a multidisciplinary expertise, from data management to biological interpretation, to support a large spectrum of collaborations from basic research to translational projects and clinical diagnostic activities.
Expertise
We have expertise in analyzing a wide range of genomic data:
- DNA sequencing (WGS, WES, Targeted)
- RNA sequencing (Bulk, Single cell)
- RiboMeth-seq
- ChIP-seq
- DSP Nanostring
- Microarrays (expression, methylation, genotyping)
We provide specific solutions to the following bioinformatics and biostatistical applications:
- Experimental design and quality control
- Alignment and variant calling (SNV/CNV/SV)
- Genome Wide Association Studies (GWAS)
- Gene expression quantification and transcriptomic signatures
- Differential gene expression and pathway enrichment analysis
- Classification, clustering and other data mining approaches
Infrastructure
The platform operates a computational and storage cluster (total of 800 cores and 1 Pb storage), application servers, LTO tapes archival system and provides access to these resources on a per-user or per-project basis. It is also working in close collaboration with the CLB hospital IT department for access to highly secured systems allowing storage of patient critical data.
Publications
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Cooperative pro-tumorigenic adaptation to oncogenic RAS through epithelial-to-mesenchymal plasticity.
De Blander H, Tonon L, …Pommier R,... , Puisieux A Sci Adv.
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Fusion-negative rhabdomyosarcoma 3D organoids to predict effective drug combinations: A proof-of-concept on cell death inducers
Savary C, …, Tonon L, … , Broutier L. Cell Rep Med.
Isocitrate dehydrogenase wt and IDHmut adult-type diffuse gliomas display distinct alterations in ribosome biogenesis and 2’O-methylation of ribosomal RNA
Paraqindes H, …, Ferrari A, Kielbassa J, Thomas E, Tonon L, Viari A, … ,Durand S. Neuro Oncol.
Different Genetic Signatures of Small-Cell Lung Cancer Characterize Anti-GABAB R and Anti-Hu Paraneoplastic Neurological Syndromes.
Epub 2023 Sep 18. PMID: 37638563.
Vogrig A, ... Sohier E, ..., Viari A, ..., Honnorat J. Ann Neurol.
MDR1-EXPRESSING CD4+ T CELLS WITH TH1.17 FEATURES RESIST TO NEOADJUVANT CHEMOTHERAPY AND ARE ASSOCIATED WITH BREAST CANCER CLINICAL RESPONSE.
Di Roio A, …, Schneider R, …, Ménétrier-Caux C. J Immunother Cancer
Spatial Transcriptomics Reveal Pitfalls and Opportunities for the Detection of Rare High-Plasticity Breast Cancer Subtypes.
Coutant A, …, Pommier R, Tonon L, Ardin M, …, Martinez P. Lab Invest.
An Early Neoplasia Index (ENI10), Based on Molecular Identity of CD10 Cells and Associated Stemness Biomarkers, is a Predictor of Patient Outcome in Many Cancers.
Guyot B, …, Thomas E, Kielbassa J, Tonon L, …, Viari A, …, Maguer-Satta V. Cancer Res Commun
Comprehensive Immune Profiling Unveils a Subset of Leiomyosarcoma with “Hot” Tumor Immune Microenvironment
Xiaolan Feng, Laurie Tonon, ..., Jean-Yves Blay. Cancers (Basel)
Dissecting the origin of heterogeneity in uterine and ovarian carcinosarcomas
Anne-Sophie Sertier, Anthony Ferrari, Roxane M. Pommier, …, Janice Kielbassa, Emilie Thomas, Laurie Tonon, Vincent Le Texier, …, Alain Viari, Maria Ouzounova, Isabelle Ray-Coquard, and Alain Puisieux. Cancer research Communications
Pembrolizumab in Lymphopenic Metastatic Breast Cancer Patients Treated with Metronomic Cyclophosphamide: A Clinical and Translational Prospective Study
Mery B,..., Ferrari A, ,…, Trédan O. Breast Cancer (Dove Med Press)
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SMAD2/3 mediate oncogenic effects of TGF-β in the absence of SMAD4.
A. Bertrand-Chapel, ..., L. Tonon, A. Viari, ..., L. Bartholin Commun Biol.
Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity.
A. Huyghe, ..., J. Kielbassa, L. Tonon, ..., F. Lavial Nat Cell Biol
Alterations in Homologous Recombination-Related Genes and Distinct Platinum Response in Metastatic Triple-Negative Breast Cancers: A Subgroup Analysis of the ProfiLER-01 Trial.
E. Bonnet, ..., A.Viari, E. Sohier, ..., O. Trédan J Pers Med
Genetic Analysis of Lung Cancer and the Germline Impact on Somatic Mutation Burden.
A.. Gabriel, ..., A-S. Sertier, A. Ferrari, A. Viari, ..., J.D. McKay J Natl Cancer Inst.
HERVs characterize normal and leukemia stem cells and represent a source of shared epitopes for cancer immunotherapy.
V. Alcazer V, ..., L. Tonon, .., A. Viari, ..., S. Depil Am J Hematol.
Signatures of Breast Carcinomas Triggering Anti-Yo-Associated Paraneoplastic Cerebellar Degeneration.
E. Peter, ..., L. Tonon, A. Viari, ..., V. Desestret Neurol Neuroimmunol Neuroinflamm.
Epithelial-to-mesenchymal transition promotes immune escape by inducing CD70 in non-small cell lung cancer
S. Ortiz-Cuaran, ..., L. Tonon, R. Pommier, ..., P. Saintigny. Eur J Cancer
Characterization of Depressive Symptoms Trajectories After Breast Cancer Diagnosis in Women in France.
C. Charles, ..., E. Thomas E., A. Viari, ..., S. Dauchy. JAMA Netw Open
Gene signature of circulating platelet-bound neutrophils is associated with poor prognosis in cancer patients
P. Lecot, M.Ardin ..., A. Viari, ..., M.-C. Michallet Int J Cancer
ZEB1 transcription factor promotes immune escape in melanoma
M. Plaschka, ..., L. Tonon, ..., J. Caramel J. ImmunoTherapy Cancer
Genomic Instability Is Defined by Specific Tumor Microenvironment in Ovarian Cancer: A Subgroup Analysis of AGO OVAR 12 Trial
J-D. Fumet, ..., E. Sohier, ..., A. duBois Cancers (Basel)
Identification of shared tumor epitopes from endogenous retroviruses inducing high-avidity cytotoxic T cells for cancer immunotherapy
P. Bonaventura, ..., L. Tonon,..., A. Viari, ..., S. Depil Sci Adv
Identification of driver genes for critical forms of COVID-19 in a deeply phenotyped young patient cohort
R. Carapito, ..., A. Viari, ..., S. Bahram Sci Transl Med
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Molecular profile to guide personalized medicine in adult patients with primary brain tumors: results from the ProfiLER trial
A. Bonneville-Levard, ... A. Viari, C. Baudet, E. Sohier, ..., J.-Y. Blay Med Oncol
Radioresistance and genomic alterations in head and neck squamous cell cancer: Sub-analysis of the ProfiLER protocol
E. Rowinski, ..., E. Sohier, ..., O. Tredan. Head & Neck
A high-risk retinoblastoma subtype with stemness features, dedifferentiated cone states and neuronal/ganglion cell gene expression
J. Liu , ..., L. Tonon, A. Viari, ..., F. Radvanyi Nature Communications
Chronic T cell receptor stimulation unmasks NK receptor signaling in peripheral T cell lymphomas via epigenetic reprogramming
S. Carras, ..., R. Pommier, ..., A. Ferrari, ..., L. Genestier The Journal of Clinical Investigation
Exploring the Complementarity of Pancreatic Ductal Adenocarcinoma Preclinical Models
O. Hoare ,..., E. Sohier, L. Tonon, ..., N. J. Dusetti Cancers (Basel)
Acquired somatic MMR deficiency is a major cause of MSI tumor in patients suspected for “Lynch-like syndrome” including young patients
C. Lefol, E. Sohier, C. Baudet, ..., A. Viari, Q. Wang Eur J Hum Genet .
OSIRIS: A Minimum Data Set for Data Sharing and Interoperability in Oncology.
Guérin J, …, Le Texier V, …, Saintigny P. JCO Clin Cancer Inform
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Ribosomal RNA 2’O-methylation as a novel layer of inter-tumour heterogeneity in breast cancer
V. Marcel, J. Kielbassa, ..., L. Tonon, ..., A. Viari, J.-J. Diaz NAR Cancer
Retrospective evaluation of whole exome, genome mutation calls in 746 cancer samples
M. H. Bailey, ..., M. B. Gerstein, L. Ding, PCAWG Consortium Nature Communications
Sex differences in oncogenic mutational processes
C. H. Li, ..., P. C. Boutros, PCAWG Consortium Nature Communications
IFN-III is selectively produced by cDC1 and predicts good clinical outcome in breast cancer.
M. Hubert, ..., J. Kielbassa, ..., and J. Valladeau-Guilemond Science Immunology
CDYL2 Epigenetically Regulates MIR124 to Control NF-kB/STAT3-Dependent Breast Cancer Cell Plasticity.
M. Siouda, ..., L. Tonon, ..., A. Viari, ... and P. Mulligan iScience
Comprehensive characterization of claudin-low breast tumors reflects the impact of the cell-of-origin on cancer evolution.
R. M. Pommier, ..., L. Tonon, J. Kielbassa, E. Thomas, A. Ferrari, A.-S. Sertier, ... and A. Puisieux Nat Communication
Pan-cancer analysis of whole genomes
ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium Nature
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Toll-like receptor 3 downregulation is an escape mechanism from apoptosis during hepatocarcinogenesis
M. Bonnin, ..., A. Viari , ..., S. Lebecque Journal of Hepathology
Repurposing rotavirus vaccines for intratumoral immunotherapy can overcome resistance to immune checkpoint blockade
T. Shekarian, ..., J. Kielbassa, ..., A. Viari, ..., A. Marabelle Science Translational Medicine
Actionable molecular alterations in advanced gynaecologic malignancies: updated results from the ProfiLER programme
R. Varnier, ..., A. Viari, ..., I. Ray-Coquard European Journal of Cancer
Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids
N. Alcala, ..., A. S. Sertier, A. Ferrari, ..., A. Viari, ..., L. Fernandez-Cuesta Nature Communications
Molecular screening program to select molecular-based recommended therapies for metastatic cancer patients: analysis from the ProfiLER trial
O. Trédan, ..., C. Baudet; E. Sohier, J.-P. Villemin, A. Viari, J.-Y. Blay and ProfiLER investigators Annals of Oncology
Neoepitopes-based vaccines: challenges and perspectives
Alcazer V, ... Tonon L., ..., Depil S. European Journal of Cancer
Mutational profile of aggressive, localised prostate cancer from african caribbean men versus european ancestry men.
Tonon L., ..., Boyault S., ,Thomas E. , Ferrari A. , Sertier A.S. , Kielbassa J., LeTexier V., ... Viari A. and Cussenot O. European Urology
The circular RNome of primary breast cancer
Smid M., ..., Viari A., ..., Martens J.W.M Genome Research
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Immunological and classical subtypes of oral premalignant lesions
Foy J.P., ..., Sohier E., Kielbassa J., Thomas E., ... Viari A., ..., Saintigny P OncoImmunology
Integrated analysis highlights APC11 protein expression as a likely new independent predictive marker for colorectal cancer
Drouet Y., ... Viari A, ... , Moyret-Lalle C. Scientific Reports
A gene-expression profiling score for prediction of outcome in patients with follicular lymphoma : a retrospective training and validation analysis in three international cohorts
Huet S., ..., Thomas E., ..., Viari, A., ... Salles G. The Lancet Oncology
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A 13-gene expression-based radioresistance score highlights the heterogeneity in the response to radiation therapy across HPV-negative HNSCC molecular subtypes
Foy J.P., ..., Kielbassa J., Thomas E., Viari A., ... and Saintigny P. BMC Medicine
The immune microenvironment of HPV-negative oral squamous cell carcinoma from never-smokers and never-drinkers patients suggests higher clinical benefit of IDO1 and PD1/PD-L1 blockade
Foy JP, ..., Thomas E., ..., Viari A, and Saintigny P. Annals of Oncologu
The immune microenvironment of HPV-negative oral squamous cell carcinoma from never-smokers and never-drinkers patients suggests higher clinical benefit of IDO1 and PD1/PD-L1 blockade
Foy, J.-P., ..., Thomas E., ..., Viari A., ... and Saintigny P. Annals of Oncology
A stemness-related ZEB1-MSRB3 axis governs cellular pliancy and breast cancer genome stability
Morel AP, ..., Thomas E, ..., Puisieux A. Nature Medicine
EZH2 alterations in follicular lymphoma: biological and clinical correlations
Huet, S., ..., Tonon L., ..., Viari A., ... and Salles G. Blood Cancer Journal
Contribution and challenges of Big Data in oncology
Saintigny, P. , ..., Ferrari A., ..., Viari A. and Puisieux A. Bulletin du Cancer
Somatic mutations reveal asymmetric cellular dynamics in the early human embryo
Ju, Y. S., ..., Viari A., ... and Stratton M.R. Nature
BCL2 mutations do not confer adverse prognosis in follicular lymphoma patients treated with rituximab.
Huet S., ..., Tonon L., ..., Viari A., ... and Sujobert P. American Journal of Hematology
A somatic-mutational process recurrently duplicates germline susceptibility loci and tissue-specific super-enhancers in breast cancers
Glodzik, D., ..., Viari A., ... and Nik-Zainal S. Nature Genetics
HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures
Davies, H., ..., Viari A., ... and Nik-Zainal S. Nature Medicine
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ZEB1-mediated melanoma cell plasticity enhances resistance to MAPK inhibitors
Richard G,..., Thomas E, ..., Caramel J. EMBO Molecular Medicine
Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration
Smid M., ..., Thomas G., Viari A., ..., and Martens W.M. Nature Communications
Author’s View: A phenotypic and mechanistic perspective on HER2-positive breast cancers heterogeneity
Ferrari A, Sertier A.S., ..., and Viari A. molecular & Cellular Oncology
HER2-positive breast cancer heterogeneity: a whole genome sequence and transcriptome perspective
Ferrari A, ..., Sertier A.S, Thomas E, Tonon L, ..., Kielbassa J., Le Texier V., ... Viari A, and Thomas G. Nature Communications
The dynamics of gene expression changes in a mouse model of oral tumorigenesis may help refine prevention and treatment strategies in patients with oral cancer
Foy JP, ..., Le Texier V, ..., Thomas E, ..., Saintigny P. Oncotarget
Landscape of somatic mutations in 560 breast cancer whole-genome sequences
Nik-Zainal S., ... Viari A., ... Thomas G. and Stratton M.R Nature
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A comprehensive assessment of somatic mutation detection in cancer using whole-genome sequencing
Alioto T.S., ..., Tonon L., Sertier A.S., ..., Gut I.G. Nature Communications
Combining tumor genome simulation with crowdsourcing to benchmark somatic single-nucleotide-variant detection
Ewing A.D., ..., ICGC-TCGA DREAM Somatic Mutation Calling Challenge participants [Sertier A.S, Ferrari A, Tonon L.], ... and Boutros P.C. Nature Methods