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Vidjil, a platform for the interactive analysis ofimmune repertoires
Marc Duez, Mathieu Giraud, Ryan Herbert, Tatiana Rocher,Mikael Salson, Florian Thonier
U. of Bristol Bonsai bioinformatics Hopital Necker
CRIStAL (Universite Lille, CNRS), Inria enfants malades
June 30, [email protected]
A strong collaboration with Lille hospital since 2011
N. Grardel
N. DuployezA. Caillault
S. Sebda
M. Figeac
C. Preudhomme
The Adaptive Immune System
TCR and Antibody Specificity – V(D)J Recombination
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
Immune Repertoire Sequencing (Rep-Seq)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 (Rep-Seq)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 (Rep-Seq)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 (Rep-Seq)Identification of all VDJ recombinations
1 000 000 VDJ = 100 000 s1 000 000 VDJ = 100 sGiraud, Salson et al., BMC Genomics, 2014
Vidjil Platform
High-throughput Repertoire Sequencing (Rep-Seq) analysis
Web Application
Algorithm
C++
Browser
Javascript, d3.js
Patient databaseServer
Python, web2py,AJAX
I All the Vidjil components are open-source (GPL v3)
I Code available from http://www.vidjil.org/ and onGitHub
I continuous integration, > 1000 unit and functional tests
Fast identification of a window centered on the CDR3Clone clustering
O(n) linear time
Giraud, Salson et al., BMC Genomics, 2014
Fast identification of a window centered on the CDR3Clone clustering
ACAC CACG ACGG CGGC GGCCGCCG TCTT CTTC TTCC TCCACCAA CAAC AACC ACCT CCTTCTTG TTGG TGGA ACTT ...
parts of V genes
ATAC TACT ACTT CCAG CAGCAGCA GCAC TGGG GGGC GGCAGCAA CAAG AAGA AGAG GAGTAGTT GTTG TTGG ...
parts of J genes
O(n) linear time
Giraud, Salson et al., BMC Genomics, 2014
Fast identification of a window centered on the CDR3Clone clustering
ACAC CACG ACGG CGGC GGCCGCCG TCTT CTTC TTCC TCCACCAA CAAC AACC ACCT CCTTCTTG TTGG TGGA ACTT ...
parts of V genes
ATAC TACT ACTT CCAG CAGCAGCA GCAC TGGG GGGC GGCAGCAA CAAG AAGA AGAG GAGTAGTT GTTG TTGG ...
parts of J genes
O(n) linear time
Giraud, Salson et al., BMC Genomics, 2014
Fast identification of a window centered on the CDR3Clone clustering
ACAC CACG ACGG CGGC GGCCGCCG TCTT CTTC TTCC TCCACCAA CAAC AACC ACCT CCTTCTTG TTGG TGGA ACTT ...
parts of V genes
ATAC TACT ACTT CCAG CAGCAGCA GCAC TGGG GGGC GGCAGCAA CAAG AAGA AGAG GAGTAGTT GTTG TTGG ...
parts of J genes
O(n) linear time
Giraud, Salson et al., BMC Genomics, 2014
Fast identification of a window centered on the CDR3Clone clustering
ACAC CACG ACGG CGGC GGCCGCCG TCTT CTTC TTCC TCCACCAA CAAC AACC ACCT CCTTCTTG TTGG TGGA ACTT ...
parts of V genes
ATAC TACT ACTT CCAG CAGCAGCA GCAC TGGG GGGC GGCAGCAA CAAG AAGA AGAG GAGTAGTT GTTG TTGG ...
parts of J genes
O(n) linear time
Giraud, Salson et al., BMC Genomics, 2014
Immune Repertoire Sequencing (Rep-Seq)Clone clustering
1 000 000 VDJ = 100 000 s
1 000 000 VDJ = 100 sGiraud, Salson et al., BMC Genomics, 2014
Vidjil analyzes recombinations on all human TR/Ig locus
Vidjil Platform
High-throughput Repertoire Sequencing (Rep-Seq) analysis
Web Application
Algorithm
C++
Browser
Javascript, d3.js
Patient databaseServer
Python, web2py,AJAX
I All the Vidjil components are open-source (GPL v3)
I Code available from http://www.vidjil.org/ and onGitHub
I continuous integration, > 1000 unit and functional tests
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
Patient database and server – Hosting
app.vidjil.orgTest server: research use onlySecure data center in Roubaix
Patient database and server – Hosting
app.vidjil.orgTest server: research use onlySecure data center in Roubaix
In your lab/hospitalA standard server is enoughSupported by local IT staff
2016: Lille, Necker
Web Application, October 2014 to June 2016Public test server app.vidjil.org, 60 users, including 20 regular users
11,000,000,000sequences
Web Application, October 2014 to June 2016Public test server app.vidjil.org, 60 users, including 20 regular users
5,000samples
Web Application, October 2014 to June 2016Public test server app.vidjil.org, 60 users, including 20 regular users
5,000samples
Web Application, October 2014 to June 2016Public test server app.vidjil.org, 60 users, including 20 regular users
5,000samples
Vidjil – What is it used for?
Diagnosis of ALLLille, Bristol,
Paris-Necker, Prague, Brussels,Rennes, Bergamo, Kiel
LLC/ClonalityLille, Brussels, Paris-Pitie
Unexpected recombinationsAmiens, Paris-Necker
RNA-SeqLyon, McGill, Gustave Roussy
Analyse your immune repertoire data with Vidjil
Process all lymphocyte receptors
Analyse your immune repertoire data with Vidjil
Process all lymphocyte receptors
Interactively browse your results1. upload, 2. process, 3. view
Analyse your immune repertoire data with Vidjil
Process all lymphocyte receptors
Interactively browse your results1. upload, 2. process, 3. view
Free softwareFeel free to use: app.vidjil.org
Feel free to contribute: git.vidjil.org
Analyse your immune repertoire data with Vidjil
Process all lymphocyte receptors
Interactively browse your results1. upload, 2. process, 3. view
Free softwareFeel free to use: app.vidjil.org
Feel free to contribute: git.vidjil.org
We hire: 1-year engineer contractPython, web, bioinfo pipelines, git, tests, agile
