Defining the progeria phenome
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Defining the progeria phenome. / Worm, Cecilie; Schambye, Maya Elena Ramirez; Mkrtchyan, Garik V.; Veviorskiy, Alexander; Shneyderman, Anastasia; Ozerov, Ivan V.; Zhavoronkov, Alex; Bakula, Daniela; Scheibye-Knudsen, Morten.
In: Aging, Vol. 16, No. 3, 2024, p. 2026-2046.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Defining the progeria phenome
AU - Worm, Cecilie
AU - Schambye, Maya Elena Ramirez
AU - Mkrtchyan, Garik V.
AU - Veviorskiy, Alexander
AU - Shneyderman, Anastasia
AU - Ozerov, Ivan V.
AU - Zhavoronkov, Alex
AU - Bakula, Daniela
AU - Scheibye-Knudsen, Morten
N1 - Publisher Copyright: © 2024 Worm et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2024
Y1 - 2024
N2 - Progeroid disorders are a heterogenous group of rare and complex hereditary syndromes presenting with pleiotropic phenotypes associated with normal aging. Due to the large variation in clinical presentation the diseases pose a diagnostic challenge for clinicians which consequently restricts medical research. To accommodate the challenge, we compiled a list of known progeroid syndromes and calculated the mean prevalence of their associated phenotypes, defining what we term the ‘progeria phenome’. The data were used to train a support vector machine that is available at https://www.mitodb.com and able to classify progerias based on phenotypes. Furthermore, this allowed us to investigate the correlation of progeroid syndromes and syndromes with various pathogenesis using hierarchical clustering algorithms and disease networks. We detected that ataxia-telangiectasia like disorder 2, spastic paraplegia 49 and Meier-Gorlin syndrome display strong association to progeroid syndromes, thereby implying that the syndromes are previously unrecognized progerias. In conclusion, our study has provided tools to evaluate the likelihood of a syndrome or patient being progeroid. This is a considerable step forward in our understanding of what constitutes a premature aging disorder and how to diagnose them.
AB - Progeroid disorders are a heterogenous group of rare and complex hereditary syndromes presenting with pleiotropic phenotypes associated with normal aging. Due to the large variation in clinical presentation the diseases pose a diagnostic challenge for clinicians which consequently restricts medical research. To accommodate the challenge, we compiled a list of known progeroid syndromes and calculated the mean prevalence of their associated phenotypes, defining what we term the ‘progeria phenome’. The data were used to train a support vector machine that is available at https://www.mitodb.com and able to classify progerias based on phenotypes. Furthermore, this allowed us to investigate the correlation of progeroid syndromes and syndromes with various pathogenesis using hierarchical clustering algorithms and disease networks. We detected that ataxia-telangiectasia like disorder 2, spastic paraplegia 49 and Meier-Gorlin syndrome display strong association to progeroid syndromes, thereby implying that the syndromes are previously unrecognized progerias. In conclusion, our study has provided tools to evaluate the likelihood of a syndrome or patient being progeroid. This is a considerable step forward in our understanding of what constitutes a premature aging disorder and how to diagnose them.
KW - aging
KW - clinical phenotype
KW - phenome
KW - premature aging
KW - progeria
U2 - 10.18632/aging.205537
DO - 10.18632/aging.205537
M3 - Journal article
C2 - 38345566
AN - SCOPUS:85185707162
VL - 16
SP - 2026
EP - 2046
JO - Aging
JF - Aging
SN - 1945-4589
IS - 3
ER -
ID: 384255284