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 (Formula presented.) 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.
- Saccharomyces cerevisiae (Baker’s yeast)
- Schizosaccharomyces pombe (fission yeast)
- genetic interactions
- machine learning model (ML model)
- protein complexes
- telomere length maintenance (TLM)