AIRRC6 - Cell-level T cell receptor sequencing at scale: 1 million cells per sample (H. Heyn)

AIRR Community
AIRR Community
539 بار بازدید - 2 سال پیش - Science, Tools & Technology Lunch
Science, Tools & Technology Lunch - May 19th, 2022
Cell-level T cell receptor sequencing at scale: 1 million cells per sample
Holger Heyn. Scientific Co-Founder. Omniscope
Introduction by Felix Breden (Professor. iReceptor)

To comprehensively chart the landscape of T cell response to a challenge, we developed Omniscope’s proprietary T cell receptor (TCR) sequencing platform OS-T. OS-T allows the simultaneous profiling of 1 million TCR sequences per sample and, thus, providing ultra-deep insights into adaptive immune repertoire dynamics. The cell-level resolution allows the sensitive counting of cells with identical TCRs for a highly quantitative assessment of T cell clonotypes. The extremely high cell number together with the sensitive quantification capacity generates a high signal-to-noise ratio for subsequent characterization and modelling of TCR sequences, going far beyond current state-of-the-art single-cell or bulk sequencing applications.

Resulting single-cell resolved T cell repertoires allow a comprehensive characterization of the adaptive repertoire breadth and the sensitive detection of repertoire dynamics (e.g., after vaccination or immunotherapy). Repertoires are presented as fully assembled V(D)J T cell receptor regions and alpha/beta chain pairs. V(D)J assignment allows the sensitive detection of clonally amplified T cells, comparative repertoire analysis and the tracking of respective clones in longitudinal cohort designs. The full-length V(D)J together with alpha/beta pairing information provides further specificity for clonality assessment and allows to determine TCR sequences for cell-based therapies

(e.g. CAR-T cells).

We applied TCR sequencing to chart the adaptive repertoire landscape of T cells infiltrating tumor microenvironments in immunotherapy mouse models and human brain metastasis. Coupled with a deep profiling of matched blood samples using the OS-T platform, we were able to detect up to 70% of putative tumor-reactive T cell in the blood, suggesting OS-T to be suitable for live-tracking immuno-therapy success and to identify therapeutically valuable TCR sequences at scale from liquid biopsies. Applied to COVID-19 patients and vaccination cohorts, OS-T presents a sensitive tool to define the magnitude and breadth of induced immunity. The profiling of 1 million cells per donor and timepoint allowed the sensitive detection of also lowly expanded clonotypes for a comprehensive charting of SARS-CoV-2 related TCR sequences and as input for machine learning approaches to predict and track individual and population immunity. OS-T applied on longitudinal patient samples throughout multiple SARS-CoV-2 infections and vaccination events is now part of our first public data release to the AIRR community.

https://www.omniscope.ai/

AIRR Community Meeting VI “Exploring New Frontiers”. La Jolla, CA. May 17-19, 2022.
https://www.antibodysociety.org/the-a...
2 سال پیش در تاریخ 1401/03/26 منتشر شده است.
539 بـار بازدید شده
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