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@ARTICLE{Krber:302875,
author = {V. Körber$^*$ and N. A. Jakobsen and N. Ansari-Pour and R.
Moore and N. Claudino$^*$ and M. Metzner and E.
Thielecke$^*$ and F. Esau$^*$ and B. Usukhbayar and M. A.
Salazar and S. Newman and B. J. L. Kendrick and A. H. Taylor
and R. Afinowi-Luitz and R. Gundle and B. Watkins and K.
Wheway and D. Beazley and S. G. Dakin and A. Palmer and A.
J. Carr and P. Vyas and T. Höfer$^*$},
title = {{D}etecting and quantifying clonal selection in somatic
stem cells.},
journal = {Nature genetics},
volume = {57},
number = {7},
issn = {1061-4036},
address = {London},
publisher = {Macmillan Publishers Limited, part of Springer Nature},
reportid = {DKFZ-2025-01415},
pages = {1718-1729},
year = {2025},
note = {#EA:B086#LA:B086# / 2025 Jul;57(7):1718-1729},
abstract = {As DNA variants accumulate in somatic stem cells, become
selected or evolve neutrally, they may ultimately alter
tissue function. When, and how, selection occurs in
homeostatic tissues is incompletely understood. Here, we
introduce SCIFER, a scalable method that identifies
selection in an individual tissue, without requiring
knowledge of the driver event. SCIFER also infers
self-renewal and mutation dynamics of the tissue's stem
cells, and the size and age of selected clones. Probing bulk
whole-genome sequencing data of nonmalignant human bone
marrow and brain, we detected pervasive selection in both
tissues. Selected clones in hematopoiesis, with or without
known drivers, were initiated uniformly across life. In the
brain, we found pre-malignant clones with glioma-initiating
mutations and clones without known drivers. In contrast to
hematopoiesis, selected clones in the brain originated
preferentially from childhood to young adulthood. SCIFER is
broadly applicable to renewing somatic tissues to detect and
quantify selection.},
cin = {B086},
ddc = {570},
cid = {I:(DE-He78)B086-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40610627},
doi = {10.1038/s41588-025-02217-y},
url = {https://inrepo02.dkfz.de/record/302875},
}