Skip to content

Commit

Permalink
BCR tutorial (#542)
Browse files Browse the repository at this point in the history
* Added beta-version v2 of bcr tutorial and adapted corresponding file accordingly; tested to add two citations into .bib file

* [pre-commit.ci] auto fixes from pre-commit.com hooks

for more information, see https://pre-commit.ci

* Fixed issues with citation, leading to a fail of build-the-docs

* Added missing citations and removed references to in-work functions

* [pre-commit.ci] auto fixes from pre-commit.com hooks

for more information, see https://pre-commit.ci

* Fixed an issue with one citation

* [pre-commit.ci] auto fixes from pre-commit.com hooks

for more information, see https://pre-commit.ci

* Updated glossary to match new BCR functionalities and offer the user easy-access literature

* Reference to new glossary entries

* [pre-commit.ci] auto fixes from pre-commit.com hooks

for more information, see https://pre-commit.ci

* Fixed faulty citation

* Update tutorial

* update tutorial

* [pre-commit.ci] auto fixes from pre-commit.com hooks

for more information, see https://pre-commit.ci

* Update notebook

* Update tutorial

* Discussion regarding bimodality of dataset

* Remove sections that will be added in separate PR

* Improve wording

* Update CHANGELOG

* Add BCR tutorial to CI

* Fix glossary link

* Glossary updates

* Update references to preprocessing tools

* Fix function reference

---------

Co-authored-by: pre-commit-ci[bot] <66853113+pre-commit-ci[bot]@users.noreply.github.com>
Co-authored-by: Gregor Sturm <[email protected]>
Co-authored-by: Gregor Sturm <[email protected]>
  • Loading branch information
4 people authored Nov 1, 2024
1 parent e5ffada commit 86e93ce
Show file tree
Hide file tree
Showing 6 changed files with 1,366 additions and 4 deletions.
1 change: 1 addition & 0 deletions .github/workflows/test-tutorials.yaml
Original file line number Diff line number Diff line change
Expand Up @@ -23,6 +23,7 @@ jobs:
tutorial:
- tutorial_3k_tcr.ipynb
- tutorial_io.ipynb
- tutorial_5k_bcr.ipynb
os:
- ubuntu-latest
python:
Expand Down
6 changes: 6 additions & 0 deletions CHANGELOG.md
Original file line number Diff line number Diff line change
Expand Up @@ -8,6 +8,12 @@ and this project adheres to [Semantic Versioning][].
[keep a changelog]: https://keepachangelog.com/en/1.0.0/
[semantic versioning]: https://semver.org/spec/v2.0.0.html

## [Unreleased]

### Documentation

- Add a tutorial for BCR analysis with Scirpy ([#542](https://github.com/scverse/scirpy/pull/542)).

## v0.19.0

### Additions
Expand Down
34 changes: 30 additions & 4 deletions docs/glossary.rst
Original file line number Diff line number Diff line change
Expand Up @@ -49,6 +49,16 @@ Glossary
:term:`CDR3<CDR>` nucleotide sequences, but might recognize the same antigen
because they have the same or similar CDR3 amino acid sequence.

This is especially relevant for BCR, because clonally related cell are likely to differ due to
:term:`somatic hypermutation <SHM>`. It is important to understand that there is currently no best practice or
go-to approach on how to define clonotype cluster for BCR, as it remains an active research
field (:cite:`Yaari.2015`). There exist many different approaches such as maximum-likelihood (:cite:`Ralph.2016`),
hierarchical clustering (:cite:`Gupta.2017`), spectral clustering (:cite:`Nouri.2018`), natural language
processing (:cite:`Lindenbaum.2021`) and network based approaches (:cite:`BashfordRogers.2013`). A recent
comparison study indicates that computationally more sophisticated clonal inference approaches do not
outperform simplistic, computational cheaper ones (:cite:`Balashova.2024`). That said, there is still a
need for more in-depth comparison studies to confirm these results.

See also: :func:`scirpy.tl.define_clonotype_clusters`.

Private clonotype
Expand Down Expand Up @@ -190,7 +200,7 @@ Glossary
Immune receptor.

BCR
B-cell receptor. A BCR consiste of two Immunoglobulin (IG) heavy chains and
B-cell receptor. A BCR consists of two Immunoglobulin (IG) heavy chains and
two IG light chains. The two light chains contain a variable region, which is
responsible for antigen recognition.

Expand All @@ -201,12 +211,24 @@ Glossary
under the `CC BY-4.0 <https://creativecommons.org/licenses/by/4.0/deed.en>`__ license,
obtained from `wikimedia commons <https://commons.wikimedia.org/w/index.php?curid=49935883>`__

SHM
Common abbreviation for "Somatic hypermutation". This process is unique to BCR and occurs as part
of affinity maturation upon antigen encounter. This process further increases the diversity of the
variable domain of the BCR and selects for cells with higher affinity. SHM introduces around one point mutation per 1000
base pairs (:cite:`Kleinstein.2003`) and is able to introduce (although rare) deletions and/or insertions (:cite:`Wilson.1998`).
Furthermore, SHM is not a stochastic process, but biased in multiple ways (e.g. intrinsic hot-spot motifs (reviewed in :cite:`Schramm.2018`))

Dual IR
:term:`IRs<IR>` with more than one pair of :term:`VJ<V(D)J>` and
:term:`VDJ<V(D)J>` sequences. While this was
previously thought to be impossible due to the mechanism of allelic exclusion
(:cite:`Brady2010-gh`), there is an increasing amound of evidence for a *bona fide*
dual-IR population (:cite:`Schuldt2019`, :cite:`Ji2010-bn`, :cite:`Vettermann2010`).
(:cite:`Brady2010-gh`), there is an increasing amount of evidence for a *bona fide*
dual-IR population (:cite:`Schuldt2019`, :cite:`Shi.2019`, :cite:`RobertaPelanda.2014`,
:cite:`Ji2010-bn`, :cite:`Vettermann2010`).

Recent evidence suggest that also B cells with three or more productively rearranged
H and/or L chains exist (:cite:`Zhu.2023`), which indicates how much of B cell development
is still unclear.

For more information on how *Scirpy* handles dual IRs, see the
page about our :ref:`IR model<receptor-model>`.
Expand Down Expand Up @@ -239,8 +261,12 @@ Glossary
Alellically included B-cells
A B cell with two pairs of :term:`IG` chains. See :term:`Dual IR`.

Isotypically included B-cells
Similar to :term:`Alellically included B-cells`, but expresses both IGL and
IGK and thus rearrangements are not on alleles of the same gene (= isotypic inclusion).

Clonotype modularity
The clonotype modularity measures how densly connected the transcriptomics
The clonotype modularity measures how densely connected the transcriptomics
neighborhood graph underlying the cells in a clonotype is. Clonotypes with
a high modularity consist of cells that are transcriptionally more similar
than that of a clonotype with a low modularity.
Expand Down
Loading

0 comments on commit 86e93ce

Please sign in to comment.