edgetics; human variome; interactome; personalized medicine; protein–protein interaction; yeast; Proteome; Humans; Genomics; Proteome/genetics; Phenotype; Saccharomyces cerevisiae/genetics; Neoplasms; Saccharomyces cerevisiae; Catalysis; Molecular Biology; Spectroscopy; Computer Science Applications; Physical and Theoretical Chemistry; Organic Chemistry; Inorganic Chemistry; General Medicine
Abstract :
[en] Understanding how genetic variation affects phenotypes represents a major challenge, particularly in the context of human disease. Although numerous disease-associated genes have been identified, the clinical significance of most human variants remains unknown. Despite unparalleled advances in genomics, functional assays often lack sufficient throughput, hindering efficient variant functionalization. There is a critical need for the development of more potent, high-throughput methods for characterizing human genetic variants. Here, we review how yeast helps tackle this challenge, both as a valuable model organism and as an experimental tool for investigating the molecular basis of phenotypic perturbation upon genetic variation. In systems biology, yeast has played a pivotal role as a highly scalable platform which has allowed us to gain extensive genetic and molecular knowledge, including the construction of comprehensive interactome maps at the proteome scale for various organisms. By leveraging interactome networks, one can view biology from a systems perspective, unravel the molecular mechanisms underlying genetic diseases, and identify therapeutic targets. The use of yeast to assess the molecular impacts of genetic variants, including those associated with viral interactions, cancer, and rare and complex diseases, has the potential to bridge the gap between genotype and phenotype, opening the door for precision medicine approaches and therapeutic development.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Laval, Florent ; Université de Liège - ULiège > TERRA Research Centre ; Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA ; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA ; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
Coppin, Georges ; Université de Liège - ULiège > GIGA ; Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA ; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA ; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
Twizere, Jean-Claude ; Université de Liège - ULiège > GIGA > GIGA Molecular Biology of Diseases - Viral Interactomes Network ; Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA ; Division of Science and Math, New York University Abu Dhabi, Abu Dhabi P.O. Box 129188, United Arab Emirates
Vidal, Marc; Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA ; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA
Language :
English
Title :
Homo cerevisiae-Leveraging Yeast for Investigating Protein-Protein Interactions and Their Role in Human Disease.
Publication date :
24 May 2023
Journal title :
International Journal of Molecular Sciences
ISSN :
1661-6596
eISSN :
1422-0067
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Switzerland
NIH - National Institutes of Health [US-MD] F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE] FRIA - Fund for Research Training in Industry and Agriculture [BE] Télévie [BE]
Funding text :
This work was supported by NIH UM1HG011989, R01GM130885, R01GM133185, R01CA266194, and U01CA232161, a Belgian American Educational Foundation doctoral research fellowship (F.L.), a Wallonia-Brussels International (WBI)-World Excellence fellowship (F.L., G.C.), the Fonds de la Recherche Scientifique (FRS-FNRS)-Télévie grant FC31747 (Crédit n° 7459421F) (F.L., J.-C.T.), the Fonds de la Recherche Scientifique (FRS-FNRS)-Fund for Research Training in Industry and Agriculture (FRIA) grant FC31543 (Crédit n° 1E00419F) (G.C.), the Fondation Léon Fredericq (F.L., J.-C.T.), a Josée and Jean Schmets Prize (F.L.) and a Herman-van Beneden Prize (F.L.).
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