T Cell receptor sequencing

Shugay M, Bagaev DV, Turchaninova MA, Bolotin DA, Britanova OV, Putintseva EV, Pogorelyy MV, Nazarov VI, Zvyagin IV, Kirgizova VI, Kirgizov KI, Skorobogatova EV, Chudakov DM.
VDJtools: Unifying Post-analysis of T Cell Receptor Repertoires.
PLoS Comput Biol. 2015 Nov 25;11(11):e1004503.

Despite the growing number of immune repertoire sequencing studies, the field still lacks software for analysis and comprehension of this high-dimensional data. Here we report VDJtools, a complementary software suite that solves a wide range of T cell receptor (TCR) repertoires post-analysis tasks, provides a detailed tabular output and publication-ready graphics, and is built on top of a flexible API. Using TCR datasets for a large cohort of unrelated healthy donors, twins, and multiple sclerosis patients we demonstrate that VDJtools greatly facilitates the analysis and leads to sound biological conclusions. VDJtools software and documentation are available at https://github.com/mikessh/vdjtools.

The T cell receptor is composed of an alpha chain and a beta chain and these are made from joining constant joing (J), Diversity (D) and variable (V) region genes. These can be sequenced and at some stage we will be able to work out what they are responding to in the future

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  • To sum up the results for multiple sclerosis dataset that are buried under technical details (common for software papers):

    Multiple sclerosis is an autoimmune disease, so probing T-cells, which are the component of adaptive immune system supposed to play key role in autoimmune diseases, seems an interesting idea.

    T-cells each carry an antigen receptor, encoding their specificity and they are initially trained to recognize foreign antigens, but can recognize self-antigens if something goes wrong, triggering autoimmune disease.

    This work was performed on large scale, as millions of T-cell receptors were profiled for a dozen of MS patients. Comparison of T-cell repertoires between MS patients and healthy control reveals the following:

    – There is some clonal expansion (division of T-cells that happens upon recognizing an antigen) which can be detected in blood of MS patients, suggesting some ongoing response.

    – These expansions are private, i.e. each patient's expanded T-cells carry receptors with unique sequences for each donor. So it is extremely hard to recognize those T-cells and specifically target them with therapy.

    – Still, there are some common features among MS patients but not healthy controls, namely so-called Variable segment parts of T-cell receptor sequences.

    – T-cells with those Variable segments appear to be more autoreactive. This was measured indirectly, by calculating the probability of those T-cells passing thymic selection which should filter-out autoreactive T-cells.

    – In MS donor post hematopoietic stem cell transplant, the level of T-cells with those Variable segments is decreased.

  • I you about a thymus transplant study in patients with type I diabetes … I would be plausible for MS as well, or not? …

By MouseDoctor



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