"The molecule's the thing": The promise of molecular modeling and dynamic simulations in aiding the prioritization and interpretation of genomic testing results [version 3; referees: 2 approved, 1 approved with reservations]

Gavin R. Oliver, Michael T. Zimmermann, Eric W Klee, Raul A. Urrutia

Research output: Contribution to journalComment/debate

1 Citation (Scopus)

Abstract

Clinical genomics is now a reality and lies at the heart of individualized medicine efforts. The success of these approaches is evidenced by the increasing volume of publications that report causal links between genomic variants and disease. In spite of early success, clinical genomics currently faces significant challenges in establishing the relevance of the majority of variants identified by next generation sequencing tests. Indeed, the majority of mutations identified are harbored by proteins whose functions remain elusive. Herein we describe the current scenario in genomic testing and in particular the burden of variants of uncertain significance (VUSs). We highlight a role for molecular modeling and molecular dynamic simulations as tools that can significantly increase the yield of information to aid in the evaluation of pathogenicity. Though the application of these methodologies to the interpretation of variants identified by genomic testing is not yet widespread, we predict that an increase in their use will significantly benefit the mission of clinical genomics for individualized medicine.

Original languageEnglish (US)
Article number766
JournalF1000Research
Volume5
DOIs
StatePublished - 2016

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Molecular modeling
Molecular Dynamics Simulation
Genomics
Molecular dynamics
Precision Medicine
Molecules
Medicine
Computer simulation
Testing
Virulence
Publications
Mutation
Proteins

ASJC Scopus subject areas

  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

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title = "{"}The molecule's the thing{"}: The promise of molecular modeling and dynamic simulations in aiding the prioritization and interpretation of genomic testing results [version 3; referees: 2 approved, 1 approved with reservations]",
abstract = "Clinical genomics is now a reality and lies at the heart of individualized medicine efforts. The success of these approaches is evidenced by the increasing volume of publications that report causal links between genomic variants and disease. In spite of early success, clinical genomics currently faces significant challenges in establishing the relevance of the majority of variants identified by next generation sequencing tests. Indeed, the majority of mutations identified are harbored by proteins whose functions remain elusive. Herein we describe the current scenario in genomic testing and in particular the burden of variants of uncertain significance (VUSs). We highlight a role for molecular modeling and molecular dynamic simulations as tools that can significantly increase the yield of information to aid in the evaluation of pathogenicity. Though the application of these methodologies to the interpretation of variants identified by genomic testing is not yet widespread, we predict that an increase in their use will significantly benefit the mission of clinical genomics for individualized medicine.",
author = "Oliver, {Gavin R.} and Zimmermann, {Michael T.} and Klee, {Eric W} and Urrutia, {Raul A.}",
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T2 - The promise of molecular modeling and dynamic simulations in aiding the prioritization and interpretation of genomic testing results [version 3; referees: 2 approved, 1 approved with reservations]

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