Vidjil, une plateforme web pour l’ etude de populations ...

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Vidjil, une plateforme web pour l’´ etude de populations lymphocytaires par NGS Aur´ elien B´ eliard, Marc Duez, Mathieu Giraud, Ryan Herbert, Tatiana Rocher, Mika¨ el Salson, Florian Thonier Bonsai bioinformatics opital Rennes CRIStAL (Universit´ e Lille, CNRS), Inria, GBMHM/Inca GBMHM/Inca June 23, 2017 [email protected]

Transcript of Vidjil, une plateforme web pour l’ etude de populations ...

Vidjil, une plateforme web pour l’etudede populations lymphocytaires par NGS

Aurelien Beliard, Marc Duez, Mathieu Giraud, Ryan Herbert,Tatiana Rocher, Mikael Salson, Florian Thonier

Bonsai bioinformatics Hopital Rennes

CRIStAL (Universite Lille, CNRS), Inria, GBMHM/Inca GBMHM/Inca

June 23, [email protected]

Conflicts of interest

MS : Novartis funded his living expenses for a 2-day workshop inDieppe, France

Vidjil, une plateforme web pour l’etudede populations lymphocytaires par NGS

Aurelien Beliard, Marc Duez, Mathieu Giraud, Ryan Herbert,Tatiana Rocher, Mikael Salson, Florian Thonier

Bonsai bioinformatics Hopital Rennes

CRIStAL (Universite Lille, CNRS), Inria, GBMHM/Inca GBMHM/Inca

June 23, [email protected]

Immune Repertoire Sequencing (RepSeq)

1. Monitor the immune re-sponse (vaccine, immunotherapy)

2. Identify markers for leukemiastratification and follow-up

The Adaptive Immune System

TCR and Antibody Specificity – V(D)J Recombination

TCR and Antibody Specificity – V(D)J Recombination

Indexing Labelled Immune Sequences

antibody

V(D)J recombinations are responsible for receptor diversity

V1 V2 V3 V65 D1 D2 D3 D27. . . J1 J2 J3 J4 J5 J6 C1. . .

Intron Intron

V D J

N N

Diversity region

V J

N

V(D)J recombinations are responsible for receptor diversity

V1 V2 V3 V65 D1 D2 D3 D27. . . J1 J2 J3 J4 J5 J6 C1. . .

Intron Intron

V D J

N N

Diversity region

V J

N

V(D)J recombinations are responsible for receptor diversity

V1 V2 V3 V65 D1 D2 D3D4J3 J4 J5 J6 C1 C2. . .

Intron Intron

V D J

N N

Diversity region

V J

N

V(D)J recombinations are responsible for receptor diversity

V1 V2 V3 V65 D1 D2 D3D4J3 J4 J5 J6 C1 C2. . .

Intron Intron

V D J

N N

Diversity region

V J

N

V(D)J recombinations are responsible for receptor diversity

V1 V2 V3 V17D4J3 J4 J5 J6 C1 C2. . .

Intron Intron

V D J

N N

Diversity region

V J

N

V(D)J recombinations are responsible for receptor diversity

V1 V2 V3 V17D4J3 J4 J5 J6 C1 C2. . .

Intron Intron

V D J

N N

Diversity region

V J

N

V(D)J recombinations are responsible for receptor diversity

V1 V2 V3 V17D4J3 J4 J5 J6 C1 C2. . .

Intron Intron

V D J

N N

Diversity region

V J

N

V(D)J recombinations are responsible for receptor diversity

V1 V2 V3 V17D4J3 J4 J5 J6 C1 C2. . .

Intron Intron

V D J

N N

Diversity region

V J

N

V(D)J recombinations are responsible for receptor diversity

V1 V2 V3 V17D4J3 J4 J5 J6 C1 C2. . .

Intron Intron

V D J

N N

Diversity region

V J

N

V(D)J recombinations are responsible for receptor diversity

V1 V2 V3 V17D4J3 J4 J5 J6 C1 C2. . .

Intron Intron

V D J

N N

Diversity region

V J

N

V(D)J recombinations are responsible for receptor diversity

V1 V2 V3 V17D4J3 J4 J5 J6 C1 C2. . .

Intron Intron

V D J

N N

Diversity region

V J

N

TCR and Antibody Specificity – V(D)J Recombination

Indexing Labelled Immune Sequences

antibody

Immune Repertoire Sequencing (RepSeq)Strategies – Sequencing millions of V(D)J recombinations from T-cells or B-cells

V D J

V D J

V D J

CDR3 specific primer

Consensus PCR primers

Capture probe

DNA

CDR3

Quantitative PCRa)

b)

c)

RNA-Seq

RNA

d)

Rep-Seq

HTS

Immune Repertoire Sequencing (RepSeq)Identification of all VDJ recombinations

1 000 000 VDJ = 100 000 s1 000 000 VDJ = 100 sGiraud, Salson et al., BMC Genomics, 2014

Immune Repertoire Sequencing (RepSeq)Identification of all VDJ recombinations

1 000 000 VDJ = 100 000 s1 000 000 VDJ = 100 sGiraud, Salson et al., BMC Genomics, 2014

Immune Repertoire Sequencing (RepSeq)Identification of all VDJ recombinations

1 000 000 VDJ = 100 000 s1 000 000 VDJ = 100 sGiraud, Salson et al., BMC Genomics, 2014

Ching-Hon Pui Childhood leukemias

0 70 140 210 280 3500,0001

0,001

0,01

0,1

1

10

100

Jours

Pou

rcen

tage

Concentration du lymphocyte cancereux

, by () — —

0 70 140 210 280 3500,0001

0,001

0,01

0,1

1

10

100

Jours

Pou

rcen

tage

Concentration du lymphocyte cancereux

, by () — —

A strong collaboration with Lille hospital since 2011

N. Grardel

N. DuployezA. Caillault

S. Sebda

M. Figeac

C. Preudhomme

Vidjil Platform

High-throughput Repertoire Sequencing (RepSeq) analysis

Web Application

Algorithm

C++

Client

Javascript, d3.js

Patient databaseServer

Python, web2py,AJAX

I all the Vidjil components are open-source (GPL v3)

I code on http://www.vidjil.org/ and on GitHub

I continuous integration, > 2, 000 unit and functional tests

Duez et al., PLOS One, 2016

Web application: traceability– Reports for medical records

Patient database and server

Autonomous RepSeq analysis pipeline in a clinical/research lab

Patient database and server

Autonomous RepSeq analysis pipeline in a clinical/research lab

Upload

Patient database and server

Autonomous RepSeq analysis pipeline in a clinical/research lab

Upload Process

Patient database and server

Autonomous RepSeq analysis pipeline in a clinical/research lab

Upload Process Analyze

Web Application, October 2014 to June 2017Public test server app.vidjil.org, >100 users, including 30 regular users

10,000samples

Web Application, October 2014 to June 2017Public test server app.vidjil.org, >100 users, including 30 regular users

1,000ALL/CLL patients at diagnosis in 5 labs

Web Application, October 2014 to June 2017Public test server app.vidjil.org, >100 users, including 30 regular users

1,000ALL/CLL patients at diagnosis in 5 labs

Web Application, October 2014 to June 2017Public test server app.vidjil.org, >100 users, including 30 regular users

1,000ALL/CLL patients at diagnosis in 5 labs

Lille, 2015: routine diagnosis of patients with ALL5 tubes, mainly BIOMED-2 primers

January-March34 patients

3 patients with Sanger failurecomparison with IMGT and igBlast

January-December120 patients

Y. Ferret, A. Caillault et al., British J. of Haematology, 2016

Analyze your immune repertoire data with Vidjil

Interactively process all lymphocyte receptorsReady-to-use platform to handle HTS/RepSeq data

1. Upload, 2. Process, 3. View and Annotate

Analyze your immune repertoire data with Vidjil

Interactively process all lymphocyte receptorsReady-to-use platform to handle HTS/RepSeq data

1. Upload, 2. Process, 3. View and Annotate

Open-source softwareFeel free to use: app.vidjil.org

Feel free to contribute: git.vidjil.org

Analyze your immune repertoire data with Vidjil

Interactively process all lymphocyte receptorsReady-to-use platform to handle HTS/RepSeq data

1. Upload, 2. Process, 3. View and Annotate

Open-source softwareFeel free to use: app.vidjil.org

Feel free to contribute: git.vidjil.org

New academic and industrial collaborationsALL/CLL diagnosis and follow-up, other pathologies

Immunological studies, immune monitoring