Fatena Bellahcene, Xavier Brochet, Laetitia Régnier, …...5' 3' An example of V-GENE V-INTRON...

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Analyse des génomes Fatena Bellahcene, Xavier Brochet, Laetitia Régnier, Marie-Paule Lefranc M2 Bioinformatique Montpellier, 13,14 et 16 janvier 2009

Transcript of Fatena Bellahcene, Xavier Brochet, Laetitia Régnier, …...5' 3' An example of V-GENE V-INTRON...

Page 1: Fatena Bellahcene, Xavier Brochet, Laetitia Régnier, …...5' 3' An example of V-GENE V-INTRON L-PART1 L-PART2 V-REGION 1st-CYS 23 2nd-CYS 104 DONOR-SPLICE ACCEPTOR-SPLICE 5'UTR 3'UTR

Analyse des génomes

Fatena Bellahcene, Xavier Brochet,

Laetitia Régnier, Marie-Paule Lefranc

M2 Bioinformatique

Montpellier, 13,14 et 16 janvier 2009

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Plan

• Analyse de génomes (en immunogénétique)• Axiomes et concepts d’IMGT-ONTOLOGY• Un outil que vous utiliserez: IMGT/V-QUEST

Notions requises et …à redécouvrir:• Locus, gènes, allèles• Orientation et localisation• Description• Classification• Fonctionalité• Relations séquences-structures-fonctions

http://www.imgt.org

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IMGT®, the international ImMunoGeneTicsinformation system®

Pourquoi IMGT® a-t-il étécréé?

http://www.imgt.org

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Immunoglobulin (IG)

B lymphocyte T lymphocyte

T cell receptor (TR) MHC

peptide

Trimolecular complex

Vertebrates

IMGT® domain: the adaptive immune responsehttp://www.imgt.org

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Bone marrow Blood Lymph nodes, spleen

V-D-J and V-J rearrangements Hypermutations, selection

http://www.imgt.org

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Spacefill 3D representation of an IgG

The Immunoglobulin FactsBook, 2001

http://www.imgt.org

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V-DOMAIN C-DOMAIN G-DOMAINs

IG and TR MHC

Structural domainshttp://www.imgt.org

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T cell receptor (TR)

Membrane IgM T cell receptor

Heavy chain

Light chain

Alpha - Beta

Gamma - Delta

Contribution of the2 V-DOMAINs

to the antigen binding siteV-J-REGION

V-J-REGION

V-D-J-REGION

V-DJ-REGION

V-DOMAIN

V-DOMAIN

Immunoglobulin (IG)

The Immunoglobulin FactsBook, 2001

http://www.imgt.org

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Immunoglobulin IgG

IMGT Repertoire, http://www.imgt.org

http://www.imgt.org

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Immunoglobulin (IG) synthesis

rearrangedDNA

mRNA

genomic DNA(IGH Locus 14q32)

5’ 3'

V D J C

5’ 3'

2 x 1012 different IGper individual

IMGT Repertoire, http://www.imgt.org

http://www.imgt.org

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Immunoglobulin (IG) synthesis

2 x 1012

DIFFERENT ANTIBODIES

5 ' 5 '3 ' 3 'x 1000

6300 POTENTIAL RECOMBINATIONS POTENTIAL RECOMBINATIONSN-DIVERSITY

SOMATIC MUTATIONS

ABOUT POSSIBILITIES3.5 x 105ABOUT POSSIBILITIES6.3 x 106

185 +165

15 0FUNCTIONAL IG GENES

5 ' 3 '

V D J C

38 - 4 6 x 2 3 x 6 30 - 35 x 5 Kappa29- -33 x 4 -5 Lambda

5 ' 3 '

V J CHEAVY CHAIN LIGHT CHAIN

IMGT Repertoire, http://www.imgt.org

http://www.imgt.org

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IMGT®• 6 Bases de données• 15 outils• 10.000 pages de ressources Web

http://www.imgt.org

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IMGT Repertoire 10.000 pages HTML Chromosomal localizationsLocus representationsGene tablesAlignments of allelesProtein displays...

IMGT Bloc-notesInteresting links…

The IMGT Immunoinformatics pageResources…

The IMGT Biotechnology pageClinical monoclonal antibodies…

IMGT EducationTutorials, IMGT Lexique…

IMGT® Ressources Webhttp://www.imgt.org

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Axiomes et concepts d’IMGT-ONTOLOGY

http://www.imgt.org

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IMGT-ONTOLOGY seven axioms:

To share, reuse and represent knowledgein Immunogenetics and Life Sciences

IMGT-ONTOLOGY

CLASSIFICATION

NUMEROTATION

DESCRIPTION

ORIENTATION

LOCALIZATION

Giudicelli and Lefranc, Bioinformatics 1999

IDENTIFICATION OBTENTION

http://www.imgt.org

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CLASSIFICATION axiom

group

subgroup

allele

locus

is a member of an instance of

is a member of an instance of

is a variant of an instance of

is ordered in an instance of

IGLV

IGLV2

IGLV2-11

IGLV2-11*02

human IGL(22q11.2)

is ordered in

is a member of

is a variant of

is a member of

gene

« Concepts » « Instances »

http://www.imgt.org

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Human IGH locus

Chromosome14q32.33

http://www.imgt.org

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IG and TR: 1512 genes and 2461 alleles from human and mouse

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CLASSIFICATION axiom

• The IMGT-ONTOLOGY main concepts of classification include ‘group’, ‘subgroup’, ‘gene’, ‘allele’.

• They allowed to set up the nomenclature for IG and TR genes (V, D, J, C genes).

• IMGT gene names were approved by HGNC in 1999 andentered in GDB, LocusLink and Entrez Gene (NCBI).

• IMGT/GENE-DB is the international reference database for IG and TR genes (direct links from Entrez Gene NCBI).

• WHO-IUIS/IMGT 2007 report (Dev. Comp. Immunol., Immunogenetics).

http://www.imgt.org

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V-GENEV-EXON

FR1-IMGT FR2-IMGT FR3-IMGT

L-PART1

V-REGION

CC5 ’UTR 3 ’UTR

CD

R3

-IMG

TDONOR-SPLICE

W

V-GENE V-EXON

FR3-IMGT CDR3-IMGT

L-PART1 DONOR-SPLICE

V-REGION FR1-IMGT

Label 1 Label 2

V-REGION CDR3-IMGT

Relations entre Labels

DESCRIPTION axiom

PROTOTYPE for a V-GENE http://www.imgt.org

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5' 3'

An example of V-GENE

V-INTRONL-PART1 V-REGIONL-PART2

1st-CYS23

2nd-CYS104DONOR

-SPLICEACCEPTOR-SPLICE

5'UTR 3'UTR

V-HEPTAMER

V-NONAMERV-SPACER

V-RS

tgagagctcc gttcctcacc atggactgga cctggaggat cctcttcttg gtggcagcag 60ccacaggtaa gaggctccct agtcccagtg atgagaaaga gattgagtcc agtccaggga 120gatctcatcc acttctgtgt tctctccaca ggagcccact cccaggtgca gctggtgcag 180tctggggctg aggtgaagaa gcctggggcc tcagtgaagg tctcctgcaa ggcttctgga 240tacaccttca ccggctacta tatgcactgg gtgcgacagg cccctggaca agggcttgag 300tggatgggat ggatcaaccc taacagtggt ggcacaaact atgcacagaa gtttcagggc 360agggtcacca tgaccaggga cacgtccatc agcacagcct acatggagct gagcaggctg 420agatctgacg acacggccgt gtattactgt gcgagagaca cagtgtgaaa acccacatcc 480tgagggtgtc agaaacccaa gggaggaggc ag

>X62106.0|HSVI2|Homo sapiens VI-2 gene for immunoglobulin heavy chain

aa gaggctccct agtcccagtg atgagaaaga gattgagtcc agtccagggagatctcatcc acttctgtgt tctctcca

tgaaa acccacatcctgagggtg

http://www.imgt.org

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5' 3'5'UTR 3'UTR

An example of D-GENE

D-REGION

5’D-HEPTAMER

5’D-NONAMER5’D-SPACER

>J00256|IGHD7-27*01|Homo sapiens D-GENE

3’D-NONAMER

3’D-HEPTAMER3’D-SPACER

ccagccgcag ggtttttggc tgagctgaga accactgtgc taactgggga cacagtgatt 60ggcagctcta caaaaaccat gctcccccgg g

c tgagctgaga ac attggcagctct

5’D-RS 3’D-RS

http://www.imgt.org

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5' 3'5'UTR 3'UTR

An example of J-GENE

>J00256|IGHJ1*01|Homo sapiens J-GENE

J-REGION

J-HEPTAMER

J-NONAMERJ-SPACER

DONOR-SPLICE

J-TRP118

accccgggct gtgggtttct gtgcccctgg ctcagggctg actcaccgtg gctgaatact 60tccagcactg gggccagggc accctggtca ccgtctcctc aggtgagtct gctgtactgg 120ggatagcggg gagccatgtg tactgggcca agcaagggct ttggcttcag 170

gcccctgg ctcagggctg act

Heavy chain WGXG (J-TRP)Light chain FGXG (J-PHE)

J-RS

http://www.imgt.org

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DESCRIPTION

IMGT/LIGM-DB

IMGT-ONTOLOGY:277 IMGT labels for sequences

285 IMGT labels for 3D structures

SO (Sequence ontology):67 IMGT labels

Avril 2007: 105 188 sequences from 150 speciesMars 2008: 121 983 sequences from 221 speciesJanv. 2009: 129 644 sequences from 229 species

http://www.imgt.org

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DESCRIPTION axiom• The IMGT-ONTOLOGY concepts of description comprise

the standardized IMGT labels and relations.

• They have allowed to describe the IG, TR and MHC sequences and 3D structures, whatever the receptor type, the chain type, or the species.

• They are particularly useful to describe IG, TR, and MHC and their complexes (IG/antigen, TR/pMHC).

• It is possible to query the IMGT® databases (IMGT/LIGM-DB for sequences, IMGT/3Dstructure-DB for 3D structures)with IMGT labels.

• Sequence Ontology (SO) includes IMGT labels.

http://imgt.cines.fr

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IMGT/V-QUEST

http://www.imgt.org

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Analysis by batches of up to 50 sequences in a single run

http://www.imgt.org

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Selection of ouputparameters http://www.imgt.org

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http://www.imgt.org

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http://www.imgt.org

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http://www.imgt.org

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View from above the CDRsSide view of the V-DOMAINs

V-J junctionV-D-J junction

V-DOMAINs: VH and V-KAPPA

Mouse(Mus musculus) E5.2Fv CDR-IMGT= Complementarity determining region (en couleurs)FR-IMGT= Framework region (en gris)

V-KAPPAVH V-KAPPAVHhttp://www.imgt.org

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The Overlanders copy - VFMC · r-, r* F

The Overlanders copy - VFMC · r-, r* F

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