Evidence map›Paper›PMID 36699357›Full record

ArticleBioinformatics advances2022

Echidna: integrated simulations of single-cell immune receptor repertoires and transcriptomes.

Jiami Han, Solène Masserey, Danielle Shlesinger, Raphael Kuhn, Chrysa Papadopoulou, Andreas Agrafiotis, Victor Kreiner, Raphael Dizerens, Kai-Lin Hong, Cédric Weber and 4 more

Open access · goldAbstract read
In one paragraph

Article in Bioinformatics advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.4field-weighted citation impact, top 41% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 6 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 2 countries.

Jiami HanDepartment of Biosystems Science and Engineering, ETH Zurich, Basel 4058, Switzerland.ORCID https://orcid.org/0000-0003-4795-1885
Solène MassereyDepartment of Biosystems Science and Engineering, ETH Zurich, Basel 4058, Switzerland.
Danielle ShlesingerDepartment of Biosystems Science and Engineering, ETH Zurich, Basel 4058, Switzerland.
Raphael KuhnDepartment of Biosystems Science and Engineering, ETH Zurich, Basel 4058, Switzerland.
Chrysa PapadopoulouDepartment of Biosystems Science and Engineering, ETH Zurich, Basel 4058, Switzerland.ORCID https://orcid.org/0000-0002-3909-7378
Andreas AgrafiotisDepartment of Biosystems Science and Engineering, ETH Zurich, Basel 4058, Switzerland.
Victor KreinerDepartment of Biosystems Science and Engineering, ETH Zurich, Basel 4058, Switzerland.
Raphael DizerensDepartment of Biosystems Science and Engineering, ETH Zurich, Basel 4058, Switzerland.
Kai-Lin HongDepartment of Biosystems Science and Engineering, ETH Zurich, Basel 4058, Switzerland.
Cédric WeberDepartment of Biosystems Science and Engineering, ETH Zurich, Basel 4058, Switzerland.ORCID https://orcid.org/0000-0003-4802-8996
Victor GreiffDepartment of Immunology, University of Oslo, Oslo 0450, Norway.ORCID https://orcid.org/0000-0003-2622-5032
Annette OxeniusInstitute of Microbiology, ETH Zurich, Zurich 8093, Switzerland.
Sai T ReddyDepartment of Biosystems Science and Engineering, ETH Zurich, Basel 4058, Switzerland.
Alexander YermanosDepartment of Biosystems Science and Engineering, ETH Zurich, Basel 4058, Switzerland.
ETH Zurich · CHUniversity of Geneva · CHUniversity of Oslo · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Motivation: Single-cell sequencing now enables the recovery of full-length immune receptor repertoires [B cell receptor (BCR) and T cell receptor (TCR) repertoires], in addition to gene expression information. The feature-rich datasets produced from such experiments require extensive and diverse computational analyses, each of which can significantly influence the downstream immunological interpretations, such as clonal selection and expansion. Simulations produce validated standard datasets, where the underlying generative model can be precisely defined and furthermore perturbed to investigate specific questions of interest. Currently, there is no tool that can be used to simulate single-cell datasets incorporating immune receptor repertoires and gene expression. Results: We developed Echidna, an R package that simulates immune receptors and transcriptomes at single-cell resolution with user-tunable parameters controlling a wide range of features such as clonal expansion, germline gene usage, somatic hypermutation, transcriptional phenotypes and spatial location. Echidna can additionally simulate time-resolved B cell evolution, producing mutational networks with complex selection histories incorporating class-switching and B cell subtype information. We demonstrated the benchmarking potential of Echidna by simulating clonal lineages and comparing the known simulated networks with those inferred from only the BCR sequences as input. Finally, we simulated immune repertoire information onto existing spatial transcriptomic experiments, thereby generating novel datasets that could be used to develop and integrate methods to profile clonal selection in a spatially resolved manner. Together, Echidna provides a framework that can incorporate experimental data to simulate single-cell immune repertoires to aid software development and bioinformatic benchmarking of clonotyping, phylogenetics, transcriptomics and machine learning strategies. Availability and implementation: The R package and code used in this manuscript can be found at github.com/alexyermanos/echidna and also in the R package Platypus (Yermanos Supplementary information: Supplementary data are available at

Identifiers

PMID36699357
PMCPMC9710610
OpenAlexW4294281364

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.