Rxivist logo

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

By Zachary Sethna, Yuval Elhanati, Curtis G Callan, Aleksandra M Walczak, Thierry Mora

Posted 12 Jul 2018
bioRxiv DOI: 10.1101/367904 (published DOI: 10.1093/bioinformatics/btz035)

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

Download data

  • Downloaded 532 times
  • Download rankings, all-time:
    • Site-wide: 30,938 out of 94,912
    • In bioinformatics: 4,027 out of 8,837
  • Year to date:
    • Site-wide: 39,912 out of 94,912
  • Since beginning of last month:
    • Site-wide: 33,432 out of 94,912

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)