SOS: online probability estimation and generation of T-and B-cell receptors

Abstract

Summary Recent advances in modelling VDJ recombination and subsequent selection of T and B cell receptors provide useful tools to analyze and compare immune repertoires across time, individuals, and tissues. A suite of tools—IGoR Marcou et al. (2018), OLGA Sethna et al. (2019) and SONIA Sethna et al. (2020)—have been publicly released to the community that allow for the inference of generative and selection models from high-throughput sequencing data. However using these tools requires some scripting or command-line skills and familiarity with complex datasets. As a result the application of the above models has not been available to a broad audience. In this application note we fill this gap by presenting Simple OLGA & SONIA (SOS), a web-based interface where users with no coding skills can compute the generation and post-selection probabilities of their sequences, as well as generate batches of synthetic sequences. The application also functions on mobile phones. Availability and implementation SOS is freely available to use at sites.google.com/view/statbiophysens/sos with source code at github.com/statbiophys/sos.

Dynamics of B cell repertoires and emergence of cross-reactive responses in patients with different severities of COVID-19

“…We characterized the probability to observe a clonal lineage ancestor in the periphery as P post s ð Þ $ P gen s ð Þe S f:features q f s ð Þ , which deviates from the inferred generation probability of the receptor P gen s ð Þ by selection factors q f ðsÞ (Isacchini et al, 2020a(Isacchini et al, , 2020b(Isacchini et al, , 2021Sethna et al, 2020). These selection factors q f ðsÞ depend on sequence features, including IGHV and IGHJ genes, HCDR3 length, and amino acid preferences at different positions in HCDR3 (STAR Methods; Elhanati et al, 2014;Isacchini et al, 2020aIsacchini et al, , 2020bIsacchini et al, , 2021Marcou et al, 2018;Sethna et al, 2020). The inferred selection models are robust to differences in the sample size of the repertoires when enough data are available to train the models (STAR Methods; Figures S4C-S4F).…”

Dynamics of B-cell repertoires and emergence of cross-reactive responses in COVID-19 patients with different disease severity

“…We characterized the probability to observe a clonal lineage ancestor in the periphery as 𝑃 post (σ) ∼ 𝑃 gen (σ)𝑒 ' (:features * ( (+) , which deviates from the inferred generation probability of the receptor 𝑃 gen (σ) by selection factors 𝑞 . (𝜎) (Isacchini et al, 2020a;Isacchini et al, 2020b;Sethna et al, 2020) . These selection factors 𝑞 .…”

“…These selection factors 𝑞 . (𝜎) depend on sequence features, including IGHV-gene and IGHJ-gene usages, HCDR3 length, and amino acid preferences at different positions in the HCDR3 (Methods) (Elhanati et al, 2014;Isacchini et al, 2020a;Isacchini et al, 2020b;Marcou et al, 2018;Sethna et al, 2020).…”

“…We characterized the probability to observe a clonal lineage ancestor in the periphery as post (σ) ∼ gen (σ) ]^: features`^( a) , which deviates from the inferred generation probability of the receptor gen (σ) by selection factors 5 ( ) (Isacchini et al, 2020a(Isacchini et al, , 2020b(Isacchini et al, , 2021Sethna et al, 2020). These selection factors 5 ( ) depend on sequence features, including IGHVgene and IGHJ-gene usages, HCDR3 length, and amino acid preferences at different positions in the HCDR3 (Methods) (Elhanati et al, 2014;Isacchini et al, 2020aIsacchini et al, , 2020bIsacchini et al, , 2021Marcou et al, 2018;Sethna et al, 2020). Importantly, the inferred selection models are robust to the differences in the sample size of the repertoires, as long as enough data is available to train the models (Methods and Fig.…”

Response to mRNA SARS‐CoV‐2 vaccination evaluated by B‐cell receptor repertoire after tixagevimab/cilgavimab administration

“…Sequences with higher pGen values are found at higher rates in any given individual. 21,30 The large increase in sequences with higher pGen values among known SARS-CoV-2-specific sequences after infection or vaccination suggests that the initial immune response upon exposure to an unknown COVID-19 antigen is often made by the more abundant common SARS-CoV-2-specific sequences. Alternatively, since the method obtains at most several hundred thousand reads from PBMCs, rare antibody sequences that are present at very low frequency may not be detected.…”