RESEARCH PROJECT

GENOMAX has a central role as the team is involved in many research programs of the research unit. The GENOMAX team also develops its own projects aiming at developing NGS-based tools or specific research programs. These projects include:

  • Methodological development to study the HLA domain,
  • Exome and RNAseq pipeline developments,
  • Disease gene identification by exome sequencing,
  • Development of multi-omics approaches to analyze complex immunological traits,
  • Deep sequencing of viral genomes,
  • Cancer genome sequencing and mutational hotspot characterization by deep sequencing.

From a global point of view, the mission of the platform is two-fold:

  • It has a strong research focus to lead or support internal projects, but also national and international collaborations.
  • GENOMAX is a fee-for-service service provider. It is an official service provider (CSP) for exome sequencing with the Ampliseq method (ThermoFisher Scientific) since 2013.

The experimental design, the analysis and interpretation of results are performed on an interactive basis between the principal investigators, technicians/engineers and bioinformatician/biostatisticians of the GENOMAX facility.

Our equipment

 Next-generation Sequencing:

  • Ion S5 (ThermoFisher Scientific)
  • Ion PGM (ThermoFisher Scientific)
  • Ion Proton (ThermoFisher Scientific)
  • NextSeq500 (Illumina)
  • Equipment for library preparation: Covaris S220, Hydroshear, Library builder, One Touch, Ion Chef (Life Technologies).
  • Informatics cluster: 4 nodes, 48 cores/2.66 GHz Westmere X5650 processor; 24 GB RAM per node; Compute cache per node: drives 2 x 1 TB, RAID 0; local storage: hard drives of  6 X 2 TB, RAID 5 (9.6 TB total); 6 Gbp backplane; QDR (40 GB/sec) Infiniband IPolB cluster private Network ; storage cluster of 48TB (33TB usable)

 Sanger sequencing:

  • 16 capillaries sequencer (ABI3130XL, ThermoFisher Scientific)
  • 96 capillaries sequencer (ABI3730XL, ThermoFisher Scientific)

High Throughput real time PCR :

  • Real time thermocycler Open array NT Cycler (ThermoFisher Scientific)
  • Accufill (ThermoFisher Scientific)

Others :

  • 5 thermocyclers (2x Veriti 96-well, 3x GenAmp 9700) (ThermoFisher Scientific)
  • Q-RT PCR instrument (ABI7000, ThermoFisher Scientific)
  • 2100 Bioanalyzer (Agilent)
  • Nanodrop 2000c (Labtech)

Services provided

  • Whole human genome re-sequencing
  • Whole exome sequencing (capture Sure Select® Agilent, TruSeq® Illumina, Ampliseq® ThermoFisher, Twist Core Exome)
  • de novo sequencing of small genomes
  • Targeted sequencing: gene panels, viruses, bacteria
  • RNA-seq: whole transcriptome and small RNA
  • Copy number variations
  • Chip-seq
  • SNPs genotyping
  • Sanger sequencing
  • Metagenomics

…and other services on demand.

COLLABORATIONS

The group has established multiple collaborations at various levels with:

  • clinical departments: local (e.g. Rheumatology, Immunology, Hematology, Internal medicine,…), national (e.g. Genetics department in Nantes and Dijon, Rheumatolgy department of Bichat hospital in Paris,…), international (e.g. Hematology department of Freiburg and Basel, Hematology/Oncology department of Boston’s Children’s hospital,…)
  • research labs : LSMBO/IPHC Strasbourg, IBMC Strasbourg, EA3072 Strasbourg, INSERM U1012 Paris-Sud, UMR1064 ITUN Nantes, EFS INSERM UMR1232 Nantes, INSERM UMR 1160 Paris St. Louis,….
  • private partners: Prenostics, Ariana Pharma, Novartis, WuxiNextCode, …

FUNDING

  • Cancéropole Grand-Est
    • Feder (Interreg V)
  • Ministère de l’enseignement supérieur et de la recherche
  • Investissements d’avenir
  • Conseil général du Bas-Rhin
  • Région Grand Est
  • Inserm
  • Université de Strasbourg / IDEX
  • MSD Avenir

PUBLICATIONS

IKZF1 Loss-of-Function Variant Causes Autoimmunity and Severe Familial Antiphospholipid Syndrome.

Dieudonné Y, Guffroy A, Vollmer O, Carapito R, Korganow AS.

J Clin Immunol. 2019 May;39(4):353-357. doi: 10.1007/s10875-019-00643-2. Epub 2019 May 14. No abstract available.

Exome sequencing identifies a novel missense variant in CTSC causing nonsyndromic aggressive periodontitis.

Molitor A, Prud’homme T, Miao Z, Conrad S, Bloch-Zupan A, Pichot A, Hanauer A, Isidor B, Bahram S, Carapito R.

J Hum Genet. 2019 Jul;64(7):689-694. doi: 10.1038/s10038-019-0615-3. Epub 2019 May 8.

HLA*LA-HLA typing from linearly projected graph alignments.

Dilthey AT, Mentzer AJ, Carapito R, Cutland C, Cereb N, Madhi SA, Rhie A, Koren S, Bahram S, McVean G, Phillippy AM.

Bioinformatics. 2019 Nov 1;35(21):4394-4396. doi: 10.1093/bioinformatics/btz235.

Multi-omics dataset to decipher the complexity of drug resistance in diffuse large B-cell lymphoma.

Fornecker LM, Muller L, Bertrand F, Paul N, Pichot A, Herbrecht R, Chenard MP, Mauvieux L, Vallat L, Bahram S, Cianférani S, Carapito R, Carapito C.

Sci Rep. 2019 Jan 29;9(1):895. doi: 10.1038/s41598-018-37273-4.

ZMIZ1 Variants Cause a Syndromic Neurodevelopmental Disorder.

Carapito R, Ivanova EL, Morlon A, Meng L, Molitor A, Erdmann E, Kieffer B, Pichot A, Naegely L, Kolmer A, Paul N, Hanauer A, Tran Mau-Them F, Jean-Marçais N, Hiatt SM, Cooper GM, Tvrdik T, Muir AM, Dimartino C, Chopra M, Amiel J, Gordon CT, Dutreux F, Garde A, Thauvin-Robinet C, Wang X, Leduc MS, Phillips M, Crawford HP, Kukolich MK, Hunt D, Harrison V, Kharbanda M; Deciphering Developmental Disorders Study; University of Washington Center for Mendelian Genomics, Smigiel R, Gold N, Hung CY, Viskochil DH, Dugan SL, Bayrak-Toydemir P, Joly-Helas G, Guerrot AM, Schluth-Bolard C, Rio M, Wentzensen IM, McWalter K, Schnur RE, Lewis AM, Lalani SR, Mensah-Bonsu N, Céraline J, Sun Z, Ploski R, Bacino CA, Mefford HC, Faivre L, Bodamer O, Chelly J, Isidor B, Bahram S.

Am J Hum Genet. 2019 Feb 7;104(2):319-330. doi: 10.1016/j.ajhg.2018.12.007. Epub 2019 Jan 10.

An unusually high substitution rate in transplant-associated BK polyomavirus in vivo is further concentrated in HLA-C-bound viral peptides.

Domingo-Calap P, Schubert B, Joly M, Solis M, Untrau M, Carapito R, Georgel P, Caillard S, Fafi-Kremer S, Paul N, Kohlbacher O, González-Candelas F, Bahram S.

PLoS Pathog. 2018 Oct 18;14(10):e1007368. doi: 10.1371/journal.ppat.1007368. eCollection 2018 Oct.

Multi-OMICS analyses unveil STAT1 as a potential modifier gene in mevalonate kinase deficiency Carapito R, Morlon A, Paul N, Vaca Jacome AS, Alsaleh G, Rolli V, Tahar O, Aouadi I, Rompais M, Delalande F, Pichot A, Georgel P, Messer L, Sibilia J, Cianferani S, Van Dorsselaer A, Bahram S BMJ Journals, 2018

Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman-Diamond–like features. Carapito R, Konantz M, Paillard C, Miao Z, Pichot A, Leduc MS, Yang Y, Bergstrom KL, Mahoney DH, Shardy DL, Alsaleh G, Naegely L, Kolmer A, Paul N, Hanauer A, Rolli V, Müller JS, Alghisi E, Sauteur L, Macquin C, Morlon A, Sancho CS, Amati-Bonneau P, Procaccio V, Mosca-Boidron AL, Marle N, Osmani N, Lefebvre O, Goetz JG, Unal S, Akarsu NA, Radosavljevic M, Chenard MP, Rialland F, Grain A, Béné MC, Eveillard M, Vincent M, Guy J, Faivre L, Thauvin-Robinet C, Thevenon J, Myers K, Fleming MD, Shimamura A, Bottollier-Lemallaz E, Westhof E, Lengerke C, Isidor B, Bahram S. JCI, 2017

A new MHC-linked susceptibility locus for primary Sjögren’s syndrome: MICA. Carapito R, Gottenberg JE, Kotova I, Untrau M, Michel S, Naegely L, Aouadi I, Kwemou M, Paul N, Pichot A, Locke J, Bowman SJ, Griffiths B, Sivils KL, Sibilia J, Inoko H, Micelli-Richard C, Nocturne G, Ota M, Ng WF, Mariette X, Bahram S. Hum Mol Genet, 2017

Next-Generation Sequencing of the HLA locus: methods and impact on HLA-typing, population genetics and disease association studies. Carapito R, Radosavljevic M, Bahram S. Human Immunology, 2016

Autosomal dominant Spondylocarpotarsal Synostosis Syndrome is caused by mutations in MYH3 in two independent families. Carapito R, Goldenberg A, Paul N, Pichot A, David A, Hamel A, Dumant-Forest C, Leroux J, Ory B, Isidor B, Bahram S. European Journal of Human Genetics, 2016

Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD. Carapito R, Jung N, Kwemou M, Untrau M, Michel S, Pichot A, Giacometti G, Macquin C, Ilias W, Morlon A, Kotova I, Apostolova P, Schmitt-Graeff A, Cesbron A, Gagne K, Oudshoorn M, van der Holt B, Labalette M, Spierings E, Picard C, Loiseau P, Tamouza R, Toubert A, Parissiadis A, Dubois V, Lafarge X, Maumy-Bertrand M, Bertrand F, Vago L, Ciceri F, Paillard C, Querol S, Sierra J, Fleischhauer K, Nagler A, Labopin M, Inoko H, von dem Borne PA, Kuball J, Ota M, Katsuyama Y, Michallet M, Lioure B, Peffault de Latour R, Blaise D, Cornelissen JJ, Yakoub-Agha I, Claas F, Moreau P, Milpied N, Charron D, Mohty M, Zeiser R, Socié G, Bahram S. Blood, 2016

Germline variation of TNFAIP3 in primary Sjögren’s syndrome-associated lymphoma. Nocturne G, Tarn J, Boudaoud S, Locke J, Miceli-Richard C, Hachulla E, Dubost JJ, Bowman S, Gottenberg JE, Criswell LA, Lessard CJ, Sivils KL, Carapito R, Bahram S, Seror R, Ng WF, Mariette X. Annals of the rheumatic diseases, 2015

Eosinophilic myositis as first manifestation in a patient with type 2 myotonic dystrophy CCTG expansion mutation and rheumatoid arthritis. Meyer A, Lannes B, Carapito R, Bahram S, Echaniz-Laguna A, Geny B, Sibilia J, Gottenberg JE. Neuromuscular disorders: NMD, 2015

On the genetics of the Silk Route: association analysis of HLA, IL10, and IL23R-IL12RB2 regions with Behcet’s disease in an Iranian population. Carapito R, Shahram F, Michel S, Le Gentil M, Radosavljevic M, Meguro A, Abdollahi BS, Inoko H, Ota M, Davatchi F, Bahram S. Immunogenetics, 2015

Polymorphisms in EGFR and IL28B are associated with spontaneous clearance in an HCV-infected iranian population. Carapito R, Poustchi H, Kwemou M, Untrau M, Sharifi AH, Merat S, Haj-Sheykholeslami A, Jabbari H, Esmaili S, Michel S, Toussaint J, Le Gentil M, Ansari-Moghaddam A, Radosavljevic M, Etemadi A, Georgel P, Malekzadeh R, Bahram S. Genes and immunity, 2015

A de novo ADCY5 mutation causes early-onset autosomal dominant chorea and dystonia. Carapito R, Paul N, Untrau M, Le Gentil M, Ott L, Alsaleh G, Jochem P, Radosavljevic M, Le Caignec C, David A, Damier P, Isidor B, Bahram S. Movement disorders: official journal of the Movement Disorder Society, 2015