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OLGA: fast computation of generation probabilities of B- and T-cell receptor amino acid sequences and motifs

Zachary Sethna, Yuval Elhanati, Curtis G Callan and 2 more (opens in a new tab)

Bioinformatics · 2019 · CC BY

doi:10.1093/bioinformatics/btz035 (opens in a new tab)

Abstract

Motivation. High-throughput sequencing of large immune repertoires has enabled the development of methods to predict the probability of generation by V(D)J recombination of T- and B-cell receptors of any specific nucleotide sequence. These generation probabilities are very non-homogeneous, ranging over 20 orders of magnitude in real repertoires. Since the function of a receptor really depends on its protein sequence, it is important to be able to predict this probability of generation at the amino acid level. However, brute-force summation over all the nucleotide sequences with the correct amino acid translation is computationally intractable. The purpose of this paper is to present a solution to this problem.

Results. We use dynamic programming to construct an efficient and flexible algorithm, called OLGA (Optimized Likelihood estimate of immunoGlobulin Amino-acid sequences), for calculating the probability of generating a given CDR3 amino acid sequence or motif, with or without V/J restriction, as a result of V(D)J recombination in B or T cells. We apply it to databases of epitope-specific T-cell receptors to evaluate the probability that a typical human subject will possess T cells responsive to specific disease-associated epitopes. The model prediction shows an excellent agreement with published data. We suggest that OLGA may be a useful tool to guide vaccine design.

Availability and implementation. Source code is available at https://github.com/zsethna/OLGA.

Supplementary information. Supplementary data are available at Bioinformatics online.

Full text

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References 47

1.
Becattini S. et al (2015 ) Functional heterogeneity of human memory cd4+ t cell clones primed by pathogens or vaccines. Science, 347, 400–406.
Not in our library10.1126/science.1260668 (opens in a new tab)
2.
Dash P. et al (2017 ) Quantifiable predictive features define epitope-specific T cell receptor repertoires. Nature, 547, 89–93.
Not in our library10.1038/nature22383 (opens in a new tab)
3.
A Public Database of Memory and Naive B-Cell Receptor Sequences · 2016
No notice
4.
Human T cell receptor occurrence patterns encode immune history, genetic background, and receptor specificity · 2018
No notice
5.
Dupic T. et al (2018 ) Genesis of the αβ T-cell receptor. arXiv: 1806.11030.
Not in our library
6.
Inferring processes underlying B-cell repertoire diversity · 2015
No notice
7.
Elhanati Y. et al (2016 ) repgenhmm: a dynamic programming tool to infer the rules of immune receptor generation from sequence data. Bioinformatics, 32, 1943–1951.
Not in our library10.1093/bioinformatics/btw112 (opens in a new tab)
8.
Elhanati Y. et al (2018 ) Predicting the spectrum of TCR repertoire sharing with a data-driven model of recombination. Immunol. Rev., 284, 167–179.
Not in our library10.1111/imr.12665 (opens in a new tab)
9.
Emerson R.O. et al (2017 ) Immunosequencing identifies signatures of cytomegalovirus exposure history and HLA-mediated effects on the T cell repertoire. Nat. Genet., 49, 659–665.
Not in our library10.1038/ng.3822 (opens in a new tab)
10.
Faham M. et al (2017 ) Discovery of T cell receptor β motifs specific to HLA-B27-positive ankylosing spondylitis by deep repertoire sequence analysis. Arthritis Rheumatol., 69, 774–784.
Not in our library10.1002/art.40028 (opens in a new tab)
11.
Freeman J.D. et al (2009 ) Profiling the T-cell receptor beta-chain repertoire by massively parallel sequencing. Genome Res., 19, 1817–1824.
Not in our library10.1101/gr.092924.109 (opens in a new tab)
12.
Fuchs Y.F. et al (2017 ) CD8+T cells specific for the islet autoantigen IGRP are restricted in their T cell receptor chain usage. Sci. Rep., 7, 1–10.
Not in our library10.1038/srep44661 (opens in a new tab)
13.
Gherardin N.A. et al (2016 ) Diversity of T cells restricted by the MHC class I-related molecule MR1 facilitates differential antigen recognition. Immunity, 44, 32–45.
Not in our library10.1016/j.immuni.2015.12.005 (opens in a new tab)
14.
Glanville J. et al (2017 ) Identifying specificity groups in the T cell receptor repertoire. Nature, 547, 94–98.
Not in our library10.1038/nature22976 (opens in a new tab)
15.
Grigaityte K. et al (2017 ) Single-cell sequencing reveals αβ chain pairing shapes the T cell repertoire. bioRxiv: 213462.
Not in our library
16.
Heather J.M. et al (2017 ) High-throughput sequencing of the T-cell receptor repertoire: pitfalls and opportunities. Brief. Bioinform., 19, 554–565.
Not in our library10.1093/bib/bbw138 (opens in a new tab)
17.
Horns F. et al (2017 ) Signatures of selection in the human antibody repertoire: selective sweeps, competing subclones, and neutral drift. bioRxiv,.
Not in our library10.1101/145052 (opens in a new tab)
18.
Howie B. et al (2015 ) High-throughput pairing of T cell receptor a and b sequences. Sci. Transl. Med., 7, 301ra131.
Not in our library10.1126/scitranslmed.aac5624 (opens in a new tab)
19.
Jiang N. et al (2013 ) Lineage structure of the human antibody repertoire in response to influenza vaccination. Sci. Transl. Med., 5, 171ra19.
Not in our library10.1126/scitranslmed.3004794 (opens in a new tab)
20.
Komech E. et al (2018 ) CD8+ T cells with characteristic TCR beta motif are detected in blood and expanded in synovial fluid of ankylosing spondylitis patients. Rheumatology (Oxford, England), 57, 1097–1104.
Not in our library10.1093/rheumatology/kex517 (opens in a new tab)
21.
Lindau P., Robins H.S. (2017 ) Advances and applications of immune receptor sequencing in systems immunology. Curr. Opin. Syst. Biol. 1, 62–68.
Not in our library
22.
How many TCR clonotypes does a body maintain? · 2016
No notice
23.
Madi A. et al (2014 ) T-cell receptor repertoires share a restricted set of public and abundant CDR3 sequences that are associated with self-related immunity. Genome Res., 24, 1603–1612.
Not in our library10.1101/gr.170753.113 (opens in a new tab)
24.
T cell receptor repertoires of mice and humans are clustered in similarity networks around conserved public CDR3 sequences · 2017
No notice
25.
High-throughput immune repertoire analysis with IGoR · 2018
No notice
26.
Mora T., Walczak A. (2018 ) Quantifying lymphocyte receptor diversity In: Das J.D., Jayaprakash C. (eds.) Systems Immunology: An Introduction to Modeling Methods for Scientists. CRC Press, pp. 185–199. https://www.crcpress.com/Systems-Immunology-An-Introduction-to-Modeling-Methods-for-Scientists/Das-Jayaprakash/p/book/9781498717403.
Not in our library
27.
Murugan A. et al (2012 ) Statistical inference of the generation probability of T-cell receptors from sequence repertoires. Proc. Natl. Acad. Sci. USA, 109, 16161–16166.
Not in our library10.1073/pnas.1212755109 (opens in a new tab)
28.
Pogorelyy M.V. et al (2017 ) Persisting fetal clonotypes influence the structure and overlap of adult human T cell receptor repertoires. PLoS Comput. Biol., 13, e1005572.
Not in our library10.1371/journal.pcbi.1005572 (opens in a new tab)
29.
Pogorelyy M.V. et al (2018a ) Method for identification of condition-associated public antigen receptor sequences. Elife, 7, 1–13.
Not in our library10.7554/elife.33050 (opens in a new tab)
30.
Pogorelyy M.V. et al (2018b ) Precise tracking of vaccine-responding T-cell clones reveals convergent and personalized response in identical twins. Proc. Natl Acad. Sci., 115, 12704–12709.
Not in our library10.1073/pnas.1809642115 (opens in a new tab)
31.
Qi Q. et al (2014 ) Diversity and clonal selection in the human T-cell repertoire. Proc. Natl. Acad. Sci. USA, 111, 13139–13144.
Not in our library10.1073/pnas.1409155111 (opens in a new tab)
32.
Robins H.S. et al (2009 ) Comprehensive assessment of T-cell receptor beta-chain diversity in alphabeta T cells. Blood, 114, 4099–4107.
Not in our library10.1182/blood-2009-04-217604 (opens in a new tab)
33.
Robins H.S. et al (2010 ) Overlap and effective size of the human CD8+ T cell receptor repertoire. Sci. Transl. Med., 2, 47ra64.
Not in our library10.1126/scitranslmed.3001442 (opens in a new tab)
34.
Seay H.R. et al (2016 ) Tissue distribution and clonal diversity of the T and B cell repertoire in type 1 diabetes. JCI Insight, 1, 1–19.
Not in our library10.1172/jci.insight.88242 (opens in a new tab)
35.
Sethna Z. et al (2017 ) Insights into immune system development and function from mouse T-cell repertoires. Proc. Natl. Acad. Sci. USA, 114, 2253–2258.
Not in our library10.1073/pnas.1700241114 (opens in a new tab)
36.
Shugay M. et al (2018 ) VDJdb: a curated database of T-cell receptor sequences with known antigen specificity. Nucleic Acids Res., 46, D419–D427.
Not in our library10.1093/nar/gkx760 (opens in a new tab)
37.
Sims J.S. et al (2016 ) Diversity and divergence of the glioma-infiltrating t-cell receptor repertoire. Proc. Natl. Acad. Sci. USA, 113, E3529–E3537.
Not in our library10.1073/pnas.1601012113 (opens in a new tab)
38.
The Past, Present, and Future of Immune Repertoire Biology – The Rise of Next-Generation Repertoire Analysis · 2013
No notice
39.
Evidence for Shaping of Light Chain Repertoire by Structural Selection · 2018
Not checked
40.
Venturi V. et al (2008 ) The role of production frequency in the sharing of simian immunodeficiency virus-specific CD8+ TCRs between macaques. J. Immunol., 181, 2597–2609.
Not in our library10.4049/jimmunol.181.4.2597 (opens in a new tab)

All 47 references

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Early life imprints the hierarchy of T cell clone sizes · 2020
Not checked
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No notice

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