DNAA short tale from bio-chemistry to immunology and statistics (in the era of big data)
Barbara Bravi and Carlos Olivares
Laboratoire de Physique de l'Ecole Normale Supérieure Paris
Threats to our immune system
Viruses Bacteria
From [5]
From [6]
Specificity on binding
From [9]
Lock key
Human genes ~ 10000
From [4]
Enormous combinatorial diversity!
Enormous combinatorial diversity!
Enormous combinatorial diversity!
IGHD4-23 IGHJ611 VDins 9 DJins
IGHV3-NL1
IGHD4-23
IGHD4-23
IGHD4-23
IGHJ6
IGHJ6
IGHJ6
From [3] Q. Marcou
IGHD4-23 IGHJ611 VDins 9 DJins
IGHV3-NL1
IGHD4-23
IGHD4-23
IGHD4-23
IGHJ6
IGHJ6
IGHJ6
T-cells
chain
AACATCACAGCCACCCAGACCGGAGACTCGGCCATCTACCTCTGTGCTGTGGATTATTATGGAGGAAGCCAAGGAAATCTCATCTTT
AAAGCTCTCTGCACATCACAGCCTCCCAGCTCAGCGATTCAGCCTCCTACATCTGTGTGGTGAACTAACGACTACAAGCTCAGCTTT
AATCTGAGGAAACCCTCTGTGCAGTGGAGTGACACAGCTGAGTACTTCTGTGCCGTGAATGCAAGGAATAACAATGACATGCGCTTT
AAATCCTTCAGTCTCAAGATCTCAGACTCACAGCTGGGGGACACTGCGATGTATTTCTGTGCTCTTAACACCGACAAGCTCATCTTT
AAGTATATCTCCTTGTTCATCAGAGACTCCCAGCCCAGTGATTCAGCCACCTACCTCTGTGGTACTAGCTATGGAAAGCTGACATTT
AATCTGAGGAAACCCTCTGTGCATTGGAGTGATGCTGCTGAGTACTTCTGTGCTGTGGTGATGGCTGCAGGCAACAAGCTAACTTTT
AAACCCTCTGTGCATTGGAGTGATGCTGCTGAGTACTTCTGTGCTGTGGGTGCGCGAATAGGCACCAATGCAGGCAAATCAACCTTT
AAACCCTCAGCCCATATGAGCGACGCGGCTGAGTACTTCTGTGCTGTGACCCCCGCTGGTGGTACTAGCTATGGAAAGCTGACATTT
AAACCCTCTGTGCATTGGAGTGATGCTGCTGAGTACTTCTGTGCTGTGGTCCCTATTTCTTCTGGTTCTGCAAGGCAACTGACCTTT
AAACATTTCTCCCTGCACATCACAGAGACCCAACCTGAAGACTCGGCTGTCTACTTCTGTGCAGCCACCGACTACAAGCTCAGCTTT
AAGACAGCCAAACATTTCTCCCTGCACATCACAGAGACCCAACCTGAAGACTCGGCTGTCTGATCAGGGAGCGACAAGCTCATCTTT
AAACATTTCTCCCTGCACATCACAGAGACCCAACCTGAAGACTCGGCTGTCTACTTCTGTGCAGCAAGCTGGGGGAAATTCCAGTTT
AAACCCTCTGTGCAGTGGAGTGACACAGCTGAGTACTTCTGTGCCGTGAACGAGTATTCAGGAGGAGGTGCTGACGGACTCACCTTT
AAGGAGCTCCAGATGAAAGACTCTGCCTCTTACCTCTGTGCTGTGAGAGATCAAGAAGCATCAGGAGGAAGCTACATACCTACATTT
AACCTTGTCATCTCCGCTTCACAACTGGGGGACTCAGCAATGTATTTCTGTGCAATGAGAGACGGTAACACCGACAAGCTCATCTTT
AAACCCTCTGTGCATTGGAGTGATGCTGCTGAGTACTTCTGTGCTGTGGCCGACCTCAATTCTGGGGGTTACCAGAAAGTTACCTTT
AAGCTCTCTGCACATCACAGCCTCCCAGCTCAGCGATTCAGCCTCCTACATCTGTGTGGTGAAGGAGGAAGCTACATACCTACATTT
AAACCCTCTGTGCATTGGAGTGATGCTGCTGAGTACTTCTGTGCTGTGGGGAAATATTCTAACTTTGGAAATGAGAAATTAACCTTT
AACTTCACCATCACAGCCTCACAAGTCGTGGACTCAGCAGTATACTTCTGTGCTCTGAGGCAAACTGGGGCAAACAACCTCTTCTTT
AAACCCTCTGTGCATTGGAGTGATGCTGCTGAGTACTTCTGTGCTGTGGGTTCGATATCTAACTTTGGAAATGAGAAATTAACCTTT
AAAGGCTCAGTTCAAGTGTCAGACTCAGCGGTGTACTTCTGTGCTCTGAGGGCCGCTGGTGGTACTAGCTATGGAAAGCTGACATTT
AATCTGAGGAAACCCTCTGTGCATTGGAGTGATGCTGCTGAGTACTTCTGTGCTGTGGGGCGGGTTAACGACTACAAGCTCAGCTTT
AACCTGAGGAAACCCTCTGTGCATTGGAGTGATGCTGCTGAGTACTTCTGTGCTGTGGGTGCTCGAAACACCGACAAGCTCATCTTT
AAAGGCTCAGTTCAAGTGTCAGACTCAGCGGTGTACTTCTGTGCTCTGAGTGAGGGGAGGTTGGGAGGATACAGCACCCTCACCTTT
AAGTATATCTCCTTGTTCATCAGAGACTCACAGCCCAGTGATTCAGCCACCTACCTCTGTGCAACCCAGGGAGGAAAGCTTATCTTC
AACCTGAGGAAACCCTCTGTGCATTGGAGTGATGCTGCTGAGTACTTCTGTGCTGTGGTTTTGAACAGAGATGACAAGATCATCTTT
AAACCCTCTGTGCATTGGAGTGATGCTGCTGAGTACTTCTGTGCTGTGGCCACGAATAGTGGAGGTAGCAACTATAAACTGACATTT
AACCTGAGGAAACCCTCTGTGCAGTGGAGTGACACAGCTGAGTACTTCTGTGCCGTGAAATTAGGCAATGCAGGCAAATCAACCTTT
AAACCATCTGCCCTTGTGAGCGACTCCGCTTTGTACTTCTGTGCTGTGAGAGCCCCTTTGACGGGAGGAGGAAACAAACTCACCTTT
15
2
10
2
1
3
1
12
2
3
13
5
3
4
31
29
5
1
2
1
3
11
19
9
1
29
7
6
1
5
Next generation sequencing has allowed the collection of an unprecedented amount of
sequence data:
from genetic sequences
Illumina tech.
T-cell selection in the Thymus: binding to ‘self’ antigens is tested
From sequence data, we can infer the SELECTION probability
TOO STRONG
TOO WEAK
Thymic selection discards between 50%-80% of T-cells! From [2]
From probability generation and selection: ask several ‘repertoire’ questions:
How public (shared among individuals) and how private (specific to individuals) immune responses?
Is sharing higher in twins?
What factors have an impact on diversity (age)?
What mutations disrupt the antigen recognition process?
Credits: [1] European Federation of Immulogical Societies https://www.inside-immunity.org/en.php [2] IMGT Education http://www.imgt.org/IMGTeducation/ [3] Quentin Marcou’s PhD thesis, 2018 [4] www.somersault1824.com/science-illustrations/ [5] https://smart.servier.com/ [6] https://opentextbc.ca/biology/chapter/23-2-adaptive-immune-response/ [7] IMGT-6Q3S.pdb [8] https://galtonboard.com/ [9] Understanding the Immune System: How It Works, National Cancer Institute, www.niaid.nih.gov, www.nci.nih.gov [10] https://smart.servier.com/
Thank you for your attention!