A comparative analysis of telomere length maintenance circuits in fission and budding yeast

The natural ends of the linear eukaryotic chromosomes are protected by telomeres, which also play an important role in aging and cancer development. Telomere length varies between species, but it is strictly controlled in all organisms. The process of Telomere Length Maintenance (TLM) involves many...

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Main Authors: Iftah Peretz, Martin Kupiec, Roded Sharan
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-11-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2022.1033113/full
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author Iftah Peretz
Martin Kupiec
Roded Sharan
author_facet Iftah Peretz
Martin Kupiec
Roded Sharan
author_sort Iftah Peretz
collection DOAJ
description The natural ends of the linear eukaryotic chromosomes are protected by telomeres, which also play an important role in aging and cancer development. Telomere length varies between species, but it is strictly controlled in all organisms. The process of Telomere Length Maintenance (TLM) involves many pathways, protein complexes and interactions that were first discovered in budding and fission yeast model organisms (Saccharomyces cerevisiae, Schizosaccharomyces pombe). In particular, large-scale systematic genetic screens in budding yeast uncovered a network of ≈500 genes that, when mutated, cause telomeres to lengthen or to shorten. In contrast, the TLM network in fission yeast remains largely unknown and systematic data is still lacking. In this work we try to close this gap and develop a unified interpretable machine learning framework for TLM gene discovery and phenotype prediction in both species. We demonstrate the utility of our framework in pinpointing the pathways by which TLM homeostasis is maintained and predicting novel TLM genes in fission yeast. The results of this study could be used for better understanding of telomere biology and serve as a step towards the adaptation of computational methods based on telomeric data for human prognosis.
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spelling doaj.art-f3f802ade01444e4acee2371f6a134202022-12-22T03:57:25ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-11-011310.3389/fgene.2022.10331131033113A comparative analysis of telomere length maintenance circuits in fission and budding yeastIftah Peretz0Martin Kupiec1Roded Sharan2The Shmunis School of Biomedicine and Cancer Research, Tel Aviv University, Tel Aviv, IsraelThe Shmunis School of Biomedicine and Cancer Research, Tel Aviv University, Tel Aviv, IsraelBlavatnik School of Computer Science, Tel Aviv University, Tel Aviv, IsraelThe natural ends of the linear eukaryotic chromosomes are protected by telomeres, which also play an important role in aging and cancer development. Telomere length varies between species, but it is strictly controlled in all organisms. The process of Telomere Length Maintenance (TLM) involves many pathways, protein complexes and interactions that were first discovered in budding and fission yeast model organisms (Saccharomyces cerevisiae, Schizosaccharomyces pombe). In particular, large-scale systematic genetic screens in budding yeast uncovered a network of ≈500 genes that, when mutated, cause telomeres to lengthen or to shorten. In contrast, the TLM network in fission yeast remains largely unknown and systematic data is still lacking. In this work we try to close this gap and develop a unified interpretable machine learning framework for TLM gene discovery and phenotype prediction in both species. We demonstrate the utility of our framework in pinpointing the pathways by which TLM homeostasis is maintained and predicting novel TLM genes in fission yeast. The results of this study could be used for better understanding of telomere biology and serve as a step towards the adaptation of computational methods based on telomeric data for human prognosis.https://www.frontiersin.org/articles/10.3389/fgene.2022.1033113/fullmachine learning model (ML model)pathwaysprotein complexestelomere length maintenance (TLM)genetic interactionsSaccharomyces cerevisiae (Baker’s yeast)
spellingShingle Iftah Peretz
Martin Kupiec
Roded Sharan
A comparative analysis of telomere length maintenance circuits in fission and budding yeast
Frontiers in Genetics
machine learning model (ML model)
pathways
protein complexes
telomere length maintenance (TLM)
genetic interactions
Saccharomyces cerevisiae (Baker’s yeast)
title A comparative analysis of telomere length maintenance circuits in fission and budding yeast
title_full A comparative analysis of telomere length maintenance circuits in fission and budding yeast
title_fullStr A comparative analysis of telomere length maintenance circuits in fission and budding yeast
title_full_unstemmed A comparative analysis of telomere length maintenance circuits in fission and budding yeast
title_short A comparative analysis of telomere length maintenance circuits in fission and budding yeast
title_sort comparative analysis of telomere length maintenance circuits in fission and budding yeast
topic machine learning model (ML model)
pathways
protein complexes
telomere length maintenance (TLM)
genetic interactions
Saccharomyces cerevisiae (Baker’s yeast)
url https://www.frontiersin.org/articles/10.3389/fgene.2022.1033113/full
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