BIOINFORMATICS
The fondation Imagine, as a partner of the University of Paris Cité and of the Faculty
of Medicine, benefits from the support of the Paris-Descartes Bioinformatics Platform
to come-along with the scientists throughout their Imagine labeled projects (support
for the experimental design planning, data handling and analysis, biological tools for data integration and interpretation).
The bioinformatics Platform collaborates with the Imagine scientists and genomic platform to develop an original pipeline for genetic linkage studies (from raw SNP microarray data
to visualisation and annotation of the candidate genomic regions via an interactive web interface). This pipeline allowed the analysis of 50 linkage projects by year.
Since 2009, the Fondation Imagine followed the “next” generation sequencer evolution
and acquired severall machines more and more powerful. The increasing amount of data generated by these technologies created new challenging issues to store, analyze, integrate and visualize pertinent information. To reach this goal, we have developed a new original pipeline to analyze resequencing projects. Our pipeline, Polypipeline is based on public tools (alignment, variation finding) as well as an original database design PolyDB (storage
and minning data) and finally a new graphical interface Polyweb (interpretation
and visualization). Our tool is completely generic and is independant from the sequencing technology used.
Our team participates also to various projects, either relating to sequencing like chip/seq, rna/seq… or more broadly to biostatistics like transcriptomic, pathway analysis… We can also help the researcher during the design step of her/his experiment to optimize the odds of positive findings.
SERVICES
NGS ANALYSIS
The bioinformatics platform provides imagine scientists (researchers and doctors) with a complete software suite allowing them to manage, analyze and visualize resequencing data (gene panels, exomes or complete genomes).
This software Polyweb includes:
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an analysis pipeline (Polypipeline) that relies on most relevant public software
and databases to realize sequence alignment, variant invocation and annotation (functional consequence, frequency, associated phenotype...).
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database developed by the platform (PolyProject) for sample monitoring.
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two graphical interfaces, PolyQuery and PolyDiag for help in interpreting
and visualizing the results.
TRANSCRIPTOMICS
Our team supports also different types of "-Seq" studies, providing expertise in methods such as ChIP-Seq or RNA-Seq.
More broadly, projects based on matrices (transcriptomics), SNP tables and functional studies (enrichment and channel analyses) are also managed by the platform.
We take care of your analysis projects from quantification to statistical analyses. We have
an Ingenuity license that we make available to researchers on a client station to help you in the biological interpretation of your results. A platform engineer is also available to train you on Ingenuity. We can also help you in the posting of your data on the public repository.
STATISTICAL ANALYSIS
Finally, we carry out statistical genetic analyses of groups of patients, commonly known
as "burden tests".
EQUIPMENT
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Cluster HP : 320 cores CPU/4TP RAM
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Serveur d’application : 40 cores et 512 Gb RAM
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Parallel Cluster File System Beegfs 50 To
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Disques de stockage (Isilon) 1,8 Po
STAFF
Patrick NITSCHKÉ
Head
Nicolas CAGNARD
Emilia PUIG-LOMBARDI
Cécile FOURRAGE
Cécile MASSON
Emmanuelle OLLIVIER
Jean-Philippe JAIS
Scientific Advisor
Margot TRAGIN
Fabienne JABOT-HANIN
Jean-Marc PLAZA
Sylvain HANEIN
Marc BRAS
Francesco CARBONE
PUBLICATIONS
Inborn errors of type I IFN immunity in patients with life-threatening COVID-19.
Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M, Chen J, Ogishi M, Sabli IKD, Hodeib S, Korol C, Rosain J, Bilguvar K, Ye J, Bolze A, Bigio B, Yang R, Arias AA, Zhou Q, Zhang Y, Onodi F, Korniotis S, Karpf L, Philippot Q, Chbihi M, Bonnet-Madin L, Dorgham K, Smith N, Schneider WM, Razooky BS, Hoffmann HH, Michailidis E, Moens L, Han JE, Lorenzo L, Bizien L, Meade P, Neehus AL, Ugurbil AC, Corneau A, Kerner G, Zhang P, Rapaport F, Seeleuthner Y, Manry J, Masson C, Schmitt Y, Schlüter A, Le Voyer T, Khan T, Li J, Fellay J, Roussel L, Shahrooei M, Alosaimi MF, Mansouri D, Al-Saud H, Al-Mulla F, Almourfi F, Al-Muhsen SZ, Alsohime F, Al Turki S, Hasanato R, van de Beek D, Biondi A, Bettini LR, D'Angio' M, Bonfanti P, Imberti L, Sottini A, Paghera S, Quiros-Roldan E, Rossi C, Oler AJ, Tompkins MF, Alba C, Vandernoot I, Goffard JC, Smits G, Migeotte I, Haerynck F, Soler-Palacin P, Martin-Nalda A, Colobran R, Morange PE, Keles S, Çölkesen F, Ozcelik T, Yasar KK, Senoglu S, Karabela ŞN, Rodríguez-Gallego C, Novelli G, Hraiech S, Tandjaoui-Lambiotte Y, Duval X, Laouénan C; COVID-STORM Clinicians; COVID Clinicians; Imagine COVID Group; French COVID Cohort Study Group; CoV-Contact Cohort; Amsterdam UMC Covid-19 Biobank; COVID Human Genetic Effort; NIAID-USUHS/TAGC COVID Immunity Group, Snow AL, Dalgard CL, Milner JD, Vinh DC, Mogensen TH, Marr N, Spaan AN, Boisson B, Boisson-Dupuis S, Bustamante J, Puel A, Ciancanelli MJ, Meyts I, Maniatis T, Soumelis V, Amara A, Nussenzweig M, García-Sastre A, Krammer F, Pujol A, Duffy D, Lifton RP, Zhang SY, Gorochov G, Béziat V, Jouanguy E, Sancho-Shimizu V, Rice CM, Abel L, Notarangelo LD, Cobat A, Su HC, Casanova JL. Imagine COVID Group : Christine Bole-Feysot, Stanislas Lyonnet*, Cécile Masson, Patrick Nitschke, Aurore Pouliet, Yoann Schmitt, Frederic Tores, Mohammed Zarhrate
Imagine Institute, Université de Paris, INSERM UMR 1163, Paris, France.
Science. 2020 Oct 23;370 (6515):eabd4570. doi: 10.1126/science.abd4570. PMID: 32972995
Autoantibodies against type I IFNs in patients with life-threatening COVID-19.
Bastard P, Rosen LB, Zhang Q, Michailidis E, Hoffmann HH, Zhang Y, Dorgham K, Philippot Q, Rosain J, Béziat V, Manry J, Shaw E, Haljasmägi L, Peterson P, Lorenzo L, Bizien L, Trouillet-Assant S, Dobbs K, de Jesus AA, Belot A, Kallaste A, Catherinot E, Tandjaoui-Lambiotte Y, Le Pen J, Kerner G, Bigio B, Seeleuthner Y, Yang R, Bolze A, Spaan AN, Delmonte OM, Abers MS, Aiuti A, Casari G, Lampasona V, Piemonti L, Ciceri F, Bilguvar K, Lifton RP, Vasse M, Smadja DM, Migaud M, Hadjadj J, Terrier B, Duffy D, Quintana-Murci L, van de Beek D, Roussel L, Vinh DC, Tangye SG, Haerynck F, Dalmau D, Martinez-Picado J, Brodin P, Nussenzweig MC, Boisson-Dupuis S, Rodríguez-Gallego C, Vogt G, Mogensen TH, Oler AJ, Gu J, Burbelo PD, Cohen JI, Biondi A, Bettini LR, D'Angio M, Bonfanti P, Rossignol P, Mayaux J, Rieux-Laucat F, Husebye ES, Fusco F, Ursini MV, Imberti L, Sottini A, Paghera S, Quiros-Roldan E, Rossi C, Castagnoli R, Montagna D, Licari A, Marseglia GL, Duval X, Ghosn J; HGID Lab; NIAID-USUHS Immune Response to COVID Group; COVID Clinicians; COVID-STORM Clinicians; Imagine COVID Group; French COVID Cohort Study Group; Milieu Intérieur Consortium; CoV-Contact Cohort; Amsterdam UMC Covid-19 Biobank; COVID Human Genetic Effort, Tsang JS, Goldbach-Mansky R, Kisand K, Lionakis MS, Puel A, Zhang SY, Holland SM, Gorochov G, Jouanguy E, Rice CM, Cobat A, Notarangelo LD, Abel L, Su HC, Casanova JL.
Imagine COVID Group : Christine Bole-Feysot, Stanislas Lyonnet*, Cécile Masson, Patrick Nitschke, Aurore Pouliet, Yoann Schmitt, Frederic Tores, Mohammed Zarhrate Imagine Institute, Université de Paris, INSERM UMR 1163, Paris, France.
Science. 2020 Oct 23;370(6515):eabd4585. doi: 10.1126/science.abd4585. PMID: 32972996.
Bi-allelic Variations of SMO in Humans Cause a Broad Spectrum of Developmental Anomalies Due to Abnormal Hedgehog Signaling.
Le TL, Sribudiani Y, Dong X, Huber C, Kois C, Baujat G, Gordon CT, Mayne V, Galmiche L, Serre V, Goudin N, Zarhrate M, Bole-Feysot C, Masson C, Nitschké P, Verheijen FW, Pais L, Pelet A, Sadedin S, Pugh JA, Shur N, White SM, El Chehadeh S, Christodoulou J, Cormier-Daire V, Hofstra RMW, Lyonnet S, Tan TY, Attié-Bitach T, Kerstjens-Frederikse WS, Amiel J, Thomas S.
Am J Hum Genet. 2020 Jun 4;106(6):779-792. doi: 10.1016/j.ajhg.2020.04.010. PMID: 32413283
Tumor invasion in draining lymph nodes is associated with Treg accumulation in breast cancer patients.
Núñez NG, Tosello Boari J, Ramos RN, Richer W, Cagnard N, Anderfuhren CD, Niborski LL, Bigot J, Meseure D, De La Rochere P, Milder M, Viel S, Loirat D, Pérol L, Vincent-Salomon A, Sastre-Garau X, Burkhard B, Sedlik C, Lantz O, Amigorena S, Piaggio E.
Nat Commun. 2020 Jun 29;11(1):3272. doi: 10.1038/s41467-020-17046-2. PMID: 32601304
Early-onset autoimmunity associated with SOCS1 haploinsufficiency.
Hadjadj J, Castro CN, Tusseau M, Stolzenberg MC, Mazerolles F, Aladjidi N, Armstrong M, Ashrafian H, Cutcutache I, Ebetsberger-Dachs G, Elliott KS, Durieu I, Fabien N, Fusaro M, Heeg M, Schmitt Y, Bras M, Knight JC, Lega JC, Lesca G, Mathieu AL, Moreews M, Moreira B, Nosbaum A, Page M, Picard C, Ronan Leahy T, Rouvet I, Ryan E, Sanlaville D, Schwarz K, Skelton A, Viallard JF, Viel S, Villard M, Callebaut I, Picard C, Walzer T, Ehl S, Fischer A, Neven B, Belot A, Rieux-Laucat F.
Nat Commun. 2020 Oct 21;11(1):5341. doi: 10.1038/s41467-020-18925-4. PMID: 33087723
Clonal tracking in gene therapy patients reveals a diversity of human hematopoietic differentiation programs.
Six E, Guilloux A, Denis A, Lecoules A, Magnani A, Vilette R, Male F, Cagnard N, Delville M, Magrin E, Caccavelli L, Roudaut C, Plantier C, Sobrino S, Gregg J, Nobles CL, Everett JK, Hacein-Bey-Abina S, Galy A, Fischer A, Thrasher AJ, André I, Cavazzana M, Bushman FD.
Blood. 2020 Apr 9;135(15):1219-1231. doi: 10.1182/blood.2019002350. PMID: 32040546
Human C-terminal CUBN variants associate with chronic proteinuria
and normal renal function.
Bedin M, Boyer O, Servais A, Li Y, Villoing-Gaudé L, Tête MJ, Cambier A, Hogan J, Baudouin V, Krid S, Bensman A, Lammens F, Louillet F, Ranchin B, Vigneau C, Bouteau I, Isnard-Bagnis C, Mache CJ, Schäfer T, Pape L, Gödel M, Huber TB, Benz M, Klaus G, Hansen M, Latta K, Gribouval O, Morinière V, Tournant C, Grohmann M, Kuhn E, Wagner T, Bole-Feysot C, Jabot-Hanin F, Nitschké P, Ahluwalia TS, Köttgen A, Andersen CBF, Bergmann C, Antignac C,Simons M
J Clin Invest. 2020 Jan 2;130(1):335-344. doi: 10.1172/JCI129937. PMID: 31613795
Improving the diagnostic efficiency of primary immunodeficiencies with targeted
next-generation sequencing
Fusaro M, Rosain J, Grandin V, Lambert N, Hanein S, Fourrage C, Renaud N, Gil M, Chevalier S, Chahla WA, Bader-Meunier B, Barlogis V, Blanche S, Boutboul D, Castelle M, Comont T, Diana JS, Fieschi C, Galicier L, Hermine O, Lefèvre-Utile A, Malphettes M, Merlin E, Oksenhendler E, Pasquet M, Suarez F, André I, Béziat V, De Saint Basile G, De Villartay JP, Kracker S, Lagresle-Peyrou C, Latour S, Rieux-Laucat F, Mahlaoui N, Bole C, Nitschke P, Hulier-Ammar E, Fischer A, Moshous D, Neven B, Alcais A, Vogt G, Bustamante J, Picard C.
Allergy Clin Immunol. 2020 Jun 10:S0091-6749(20)30816-2.
Gene Mutations in a Large Cohort of Predominantly Caucasian Patients
with Hidradenitis Suppurativa. Low Prevalence of GSC.
Duchatelet S, Miskinyte S, Delage M, Ungeheuer MN, Lam T, Benhadou F, Del Marmol V, Vossen ARJV, Prens EP, Cogrel O, Beylot-Barry M, Girard C, Vidil J, Join-Lambert O, Parisot M, Nitschké P, Hanein S, Fraitag S, Van der Zee HH, Bessis D, Damiani G, Altomare A, Liao YH, Nikolakis G, Zouboulis CC, Nassif A, Hovnanian A.
J Invest Dermatol. 2020 Oct;140(10):2085-2088.e14.
A novel pathogenic variant in DYNC1H1 causes various upper and lower
motor neuron anomalies.
Viollet LM, Swoboda KJ, Mao R, Best H, Ha Y, Toutain A, Guyant-Marechal L, Laroche-Raynaud C, Ghorab K, Barthez MA, Pedespan JM, Hernandorena X, Lia AS, Deleuze JF, Masson C, Nelson I, Nectoux J, Si Y.
Eur J Med Genet. 2020 Dec;63(12):104063. doi: 10.1016/j.ejmg.2020.104063. Epub 2020 Sep 16. PMID: 32947049
Fetal megacystis-microcolon: Genetic mutational spectrum and identification of PDCL3 as a novel candidate gene.
Billon C, Molin A, Poirsier C, Clemenson A, Dauge C, Grelet M, Sigaudy S, Patrier S, Goldenberg A, Layet V, Tantau J, Fleury C, Liard A, Diguet A, Fritih R, Verspyck E, Rendu J, Boutaud L, Tessier A, Thomas S, Razavi F, Achaiaa A, Elkhartoufi N, Hakkakian L, Magnin E, Bôle-Feysot C, Masson C, Ville Y, Roth P, Prieur F, Bessieres B, Bonniere M, Attie-Bitach T.
Clin Genet. 2020 Sep;98(3):261-273. doi: 10.1111/cge.13801. PMID: 32621347
Editing a γ-globin repressor binding site restores fetal hemoglobin synthesis
and corrects the sickle cell disease phenotype.
Weber L, Frati G, Felix T, Hardouin G, Casini A, Wollenschlaeger C, Meneghini V, Masson C, De Cian A, Chalumeau A, Mavilio F, Amendola M, Andre-Schmutz I, Cereseto A, El Nemer W, Concordet JP, Giovannangeli C, Cavazzana M, Miccio A.
Sci Adv. 2020 Feb 12;6(7):eaay9392. doi: 10.1126/sciadv.aay9392. PMID: 32917636
Somatic reversion of pathogenic DOCK8 variants alters lymphocyte differentiation
and function to effectively cure DOCK8 deficiency.
Pillay BA, Fusaro M, Gray PE, Statham AL, Burnett L, Bezrodnik L, Kane A, Tong WWY, Abdo C, Winter S, Chevalier S, Levy R, Masson C, Schmitt Y, Bole-Feysot C, Malphettes M, Macintyre E, de Villartay JP, Ziegler JB, Smart JM, Peake J, Aghamohammadi A, Hammarström L, Abolhassani H, Picard C, Fischer A, Latour S, Neven B, Tangye S, Ma CS.
J Clin Invest. 2020 Dec 8:142434. doi: 10.1172/JCI142434. PMID: 33290277
From Dysgammaglobulinemia to Autosomal-Dominant Activation-Induced Cytidine Deaminase Deficiency: Unraveling an Inherited Immunodeficiency after 50 Years.
Fadlallah J, Chentout L, Boisson B, Pouliet A, Masson C, Morin F, Durandy A, Casanova JL, Oksenhendler E, Kracker S.
J Pediatr. 2020 Aug;223:207-211.e1. doi: 10.1016/j.jpeds.2020.03.024. PMID: 32423680
High Diagnostic Yield of Targeted Next-Generation Sequencing in a Cohort of Patients with Congenital Hypothyroidism Due to Dyshormonogenesis.
Athanasia STOUPA, Ghada Al Hage Chehade, Rim Chaabane, Dulanjalee Kariyawasam, Gabor Szinnai, Sylvain Hanein, Christine Bole-Feysot, Cecile Fourrage, Patrick Nitschke, Caroline Thalassinos, Graziella Pinto, Mouna Mnif, Sabine Baron, Marc De Kerdanet, Rachel Reynaud, Pascal Barat, Mongia Hachicha, Neila Belguith, Michel Polak, Aurore CARRE
Frontiers in Endocrinology, section Thyroid Endocrinology | doi: 10.3389/fendo.2020.545339
Loss-of-Function Mutations in NR4A2 Cause Dopa-Responsive Dystonia Parkinsonism.
Wirth T, Mariani LL, Bergant G, Baulac M, Habert MO, Drouot N, Ollivier E, Hodžić A, Rudolf G, Nitschke P, Rudolf G, Chelly J, Tranchant C, Anheim M, Roze E.
Mov Disord. 2020 May;35(5):880-885. doi: 10.1002/mds.27982. Epub 2020 Jan 10. PMID: 31922365
Increased diagnostic yield in complex dystonia through exome sequencing.
Wirth T, Tranchant C, Drouot N, Keren B, Mignot C, Cif L, Lefaucheur R, Lion-François L, Méneret A, Gras D, Roze E, Laroche C, Burbaud P, Bannier S, Lagha-Boukbiza O, Spitz MA, Laugel V, Bereau M, Ollivier E, Nitschke P, Doummar D, Rudolf G, Anheim M, Chelly
J. Parkinsonism Relat Disord. 2020 May;74:50-56. doi: 10.1016/j.parkreldis.2020.04.003. Epub 2020 Apr 20. PMID: 32334381
NHP2 deficiency impairs rRNA biogenesis and causes pulmonary fibrosis
and Høyeraal-Hreidarsson syndrome.
Benyelles M, O'Donohue MF, Kermasson L, Lainey E, Borie R, Lagresle-Peyrou C, Nunes H, Cazelles C, Fourrage C, Ollivier E, Marcais A, Gamez AS, Morice-Picard F, Caillaud D, Pottier N, Ménard C, Ba I, Fernandes A, Crestani B, de Villartay JP, Gleizes PE, Callebaut I, Kannengiesser C, Revy P.
Hum Mol Genet. 2020 Apr 15;29(6):907-922. doi: 10.1093/hmg/ddaa011. PMID: 31985013
MeCP2 is involved in random mono-allelic expression for a subset of human
autosomal genes.
Brousseau M, Nectoux J, Saintpierre B, Lebrun N, Cagnard N, Izac B, Ollivier E,
Letourneur F, Bienvenu T.
Biochim Biophys Acta Mol Basis Dis. 2020 Jun 1;1866(6):165730. doi: 10.1016/j.bbadis.2020.165730. PMID: 32070770
Unique inflammatory signature in haemophilic arthropathy: miRNA changes
due to interaction between blood and fibroblast-like synoviocytes.
Mignot S, Cagnard N, Albaud B, Bally C, Siavellis J, Hermine O, Frenzel L.
J Cell Mol Med. 2020 Nov 7;24(24):14453-66. doi: 10.1111/jcmm.16068. PMID: 33159500