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Collaborative Research: GCR: Understanding Epistasis: the Key for Genotype to Phenotype Mapping

Collaborative Research: GCR: Understanding Epistasis: the Key for Genotype to Phenotype Mapping
合作研究:GCR:了解上位性:基因型到表型作图的关键
批准号:
1934848
负责人:
Sudhir Kumar
金额:
$320.22万
依托单位:
依托单位国家:
美国
项目类别:
Continuing Grant
财政年份:
2019
资助国家:
美国
项目状态:
未结题
起止时间:
2019-10-01 至 2025-09-30

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中文摘要
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英文摘要
This Growing Convergence Research project is seeking to explain the resilience of genotype-phenotype maps through functional epistasis via a convergence of three overlapping fields of investigation: molecular evolution, data science and statistical physics. The project is motivated by an unanticipated amount of variation in populations, gene families, and phylogenetic groups revealed by DNA sequencing of genes, individuals, and species. These voluminous data on variation are posing unexpected challenges to the (nearly) neutral theory of molecular evolution that explains the fate of new mutations in a population through random genetic drift and purifying selection. The research team will employ mechanistic models of epistasis, co-evolutionary processes, and deep learning. Deep integration across disciplines will be key for exploring the pivotal role of epistasis and, ultimately, for interrogating the most fundamental rules of life. The research team proposes a transdisciplinary project to set the foundations for a novel neutral-by-epistasis theory of molecular evolution. This team hypothesizes that a vast majority of population variation and species differences are due to random genetic drift of mutations that are neutral by epistasis, even though each may be individually detrimental. The new neutral-by-epistasis theory unites both neutral and nearly-neutral theories of molecular evolution and has the potential for a paradigm shift in which epistatic interactions between positions, rather than any individual position are the primary unit of comparative analysis.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
期刊论文(20)
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会议论文
DOI: 10.1371/journal.pcbi.1010006
发表时间: 2022-04
期刊: PLoS computational biology
影响因子: 4.3
作者: []
通讯作者:
DOI: 10.1093/molbev/msab118
发表时间: 2021-07-29
期刊: Molecular biology and evolution
影响因子: 10.7
作者: [Kumar S, Tao Q, Weaver S, Sanderford M, Caraballo-Ortiz MA, Sharma S, Pond SLK, Miura S]
通讯作者: Miura S
DOI: 10.1073/pnas.1921727117
发表时间: 2020
期刊: Proceedings of the National Academy of Sciences
影响因子: --
作者: [Levy, Ronald M.]
通讯作者: Levy, Ronald M.
DOI: 10.1002/wcms.1537
发表时间: 2021-06
期刊: Wiley Interdisciplinary Reviews: Computational Molecular Science
影响因子: --
作者: [Ruiyu Wang;M. Klein;V. Carnevale;E. Borguet]
通讯作者: Ruiyu Wang;M. Klein;V. Carnevale;E. Borguet
7
    RAPID: Reconstructing the contemporary history and progenitor of SARS-CoV-2 strains causing COVID-19
    • 批准号:
      2034228
    • 项目类别:
      Standard Grant
    • 资助金额:
      $20.0万
    • 财政年份:
      2020
    • 负责人:
      Sudhir Kumar
    • 依托单位:
    ABI Development: Open-source, extensible, and cross-platform MEGA
    • 批准号:
      1661218
    • 项目类别:
      Standard Grant
    • 资助金额:
      $99.84万
    • 财政年份:
      2017
    • 负责人:
      Sudhir Kumar
    • 依托单位:
    Collaborative Research: ABI Development: Enabling discovery across disciplines through a synthesis of time-calibrated evolutionary histories
    • 批准号:
      1445187
    • 项目类别:
      Continuing Grant
    • 资助金额:
      $52.76万
    • 财政年份:
      2014
    • 负责人:
      Sudhir Kumar
    • 依托单位:
    Collaborative Research: ABI Development: Enabling discovery across disciplines through a synthesis of time-calibrated evolutionary histories
    • 批准号:
      1262440
    • 项目类别:
      Continuing Grant
    • 资助金额:
      $57.86万
    • 财政年份:
      2013
    • 负责人:
      Sudhir Kumar
    • 依托单位:
    国内基金
    海外基金
    Research on Quantum Field Theory without a Lagrangian Description
    • 批准号:
      24ZR1403900
    • 项目类别:
      省市级项目
    • 资助金额:
      --
    • 批准年份:
      2024
    • 负责人:
      SATOSHI NAWATA
    • 依托单位:
    Cell Research
    Cell Research
    Cell Research (细胞研究)