Homo cerevisiae-Leveraging Yeast for Investigating Protein-Protein Interactions and Their Role in Human Disease.
Homo cerevisiae-Leveraging Yeast for Investigating Protein-Protein Interactions and Their Role in Human Disease.
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DOI：
10.3390/ijms24119179
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发表时间：
2023-05-24
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
理解遗传变异如何影响表型是一项重大挑战，特别是在人类疾病的背景下。虽然许多疾病相关基因已被确定，但大多数人类变异的临床意义仍然未知。尽管基因组学取得了无与伦比的进步，但功能分析往往缺乏足够的吞吐量，阻碍了有效的变异功能化。迫切需要开发更有效的、高通量的方法来表征人类遗传变异。在这里，我们回顾酵母如何帮助解决这一挑战，作为一个有价值的模式生物和作为研究遗传变异的表型扰动的分子基础的实验工具。在系统生物学中，酵母作为一个高度可扩展的平台发挥了关键作用，它使我们能够获得广泛的遗传和分子知识，包括在各种生物体的蛋白质组尺度上构建全面的相互作用组图。通过利用相互作用组网络，人们可以从系统的角度来看待生物学，揭示遗传疾病的分子机制，并确定治疗靶点。利用酵母来评估遗传变异的分子影响，包括那些与病毒相互作用、癌症以及罕见和复杂疾病相关的基因变异，有可能弥合基因型和表型之间的差距，为精准医学方法和治疗开发打开大门。
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.
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影响因子：
4.3
作者：
Barshir R;Shwartz O;Smoly IY;Yeger-Lotem E
通讯作者：
Yeger-Lotem E
影响因子：
9.9
作者：
Cox, Robert Sidney 3rd;Surette, Michael G;Elowitz, Michael B
通讯作者：
Elowitz, Michael B
影响因子：
3.9
作者：
Amberger, Joanna;Bocchini, Carol;Hamosh, Ada
通讯作者：
Hamosh, Ada
DOI：
10.1073/pnas.82.1.43
发表时间：
1985-01-01
影响因子：
11.1
作者：
BRAM, RJ;KORNBERG, RD
通讯作者：
KORNBERG, RD
DOI：
10.1126/science.1180823
发表时间：
2010-01-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Costanzo M;Baryshnikova A;Bellay J;Kim Y;Spear ED;Sevier CS;Ding H;Koh JL;Toufighi K;Mostafavi S;Prinz J;St Onge RP;VanderSluis B;Makhnevych T;Vizeacoumar FJ;Alizadeh S;Bahr S;Brost RL;Chen Y;Cokol M;Deshpande R;Li Z;Lin ZY;Liang W;Marback M;Paw J;San Luis BJ;Shuteriqi E;Tong AH;van Dyk N;Wallace IM;Whitney JA;Weirauch MT;Zhong G;Zhu H;Houry WA;Brudno M;Ragibizadeh S;Papp B;Pál C;Roth FP;Giaever G;Nislow C;Troyanskaya OG;Bussey H;Bader GD;Gingras AC;Morris QD;Kim PM;Kaiser CA;Myers CL;Andrews BJ;Boone C
通讯作者：
Boone C