Evidence map›Paper›PMID 35764632›Full record

ArticleNature communications2022

Clonal reconstruction from co-occurrence of vector integration sites accurately quantifies expanding clones in vivo.

Sebastian Wagner, Christoph Baldow, Andrea Calabria, Laura Rudilosso, Pierangela Gallina, Eugenio Montini, Daniela Cesana, Ingmar Glauche

Abstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
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

8 authors.

Sebastian Wagner *Institute for Medical Informatics and Biometry, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.ORCID 0000-0001-6468-4833
Christoph Baldow *Institute for Medical Informatics and Biometry, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.ORCID 0000-0002-4366-1453
Andrea CalabriaSan Raffaele-Telethon Institute for Gene Therapy (SR-Tiget), IRCCS Ospedale San Raffaele, Milan, Italy.ORCID 0000-0003-3515-3384
Laura RudilossoSan Raffaele-Telethon Institute for Gene Therapy (SR-Tiget), IRCCS Ospedale San Raffaele, Milan, Italy.
Pierangela GallinaSan Raffaele-Telethon Institute for Gene Therapy (SR-Tiget), IRCCS Ospedale San Raffaele, Milan, Italy.
Eugenio MontiniSan Raffaele-Telethon Institute for Gene Therapy (SR-Tiget), IRCCS Ospedale San Raffaele, Milan, Italy.ORCID 0000-0003-1771-6067
Daniela CesanaSan Raffaele-Telethon Institute for Gene Therapy (SR-Tiget), IRCCS Ospedale San Raffaele, Milan, Italy.ORCID 0000-0001-6366-4224
Ingmar GlaucheInstitute for Medical Informatics and Biometry, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Dresden, Germany. ingmar.glauche@tu-dresden.de.ORCID 0000-0002-2524-1199

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

High transduction rates of viral vectors in gene therapies (GT) and experimental hematopoiesis ensure a high frequency of gene delivery, although multiple integration events can occur in the same cell. Therefore, tracing of integration sites (IS) leads to mis-quantification of the true clonal spectrum and limits safety considerations in GT. Hence, we use correlations between repeated measurements of IS abundances to estimate their mutual similarity and identify clusters of co-occurring IS, for which we assume a clonal origin. We evaluate the performance, robustness and specificity of our methodology using clonal simulations. The reconstruction methods, implemented and provided as an R-package, are further applied to experimental clonal mixes and preclinical models of hematopoietic GT. Our results demonstrate that clonal reconstruction from IS data allows to overcome systematic biases in the clonal quantification as an essential prerequisite for the assessment of safety and long-term efficacy of GT involving integrative vectors.

Indexed as

Genetic TherapyGenetic VectorsClone CellsGene Transfer Techniques

Identifiers

PMID35764632
PMCPMC9240075

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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.