Cited by 161Genomics and Rare DiseasesCRISPR and Genetic EngineeringGenetic Associations and Epidemiology

The power of multiplexed functional analysis of genetic variants

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Gasperini, Molly, Starita, Lea, Shendure, Jay·2016·Nature Protocols

Abstract

New technologies have recently enabled saturation mutagenesis and functional analysis of nearly all possible variants of regulatory elements or proteins of interest in single experiments. Here we discuss the past, present, and future of such multiplexed (functional) assays for variant effects (MAVEs). MAVEs provide detailed insight into sequence-function relationships, and they may prove critical for the prospective clinical interpretation of genetic variants.

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Crossref · 10.1038/nprot.2016.135

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  • A clear strength of MPRAs is their ability to simultaneously test large numbers of sequences for regulatory activity via a relatively straightforward, widely accessible toolkit.

    “A clear strength of MPRAs is their ability to simultaneously test large numbers of sequences for regulatory activity via a relatively straightforward, widely accessible toolkit (i.e. oligonucleotide synthesis, molecular biology, cell culture, and sequencing)175.”

    From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [175]

    The Abstract says massively parallel reporter assays map regulatory sequence–function relationships and can assess hundreds to thousands of variants in one experiment. The Construction of a variant library and Sequencing to count variant frequency sections describe oligonucleotide libraries and sequencing, but the paper does not establish that the toolkit is relatively straightforward or widely accessible; it describes library construction as challenging. (LLM, conf=0.84)

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Research works printed but not linked: 1

  1. [51]Ireland WT & Kinney JB Sort-Seq Tools: sequence-function relationship modeling for massively parallel assays Preprint at http://biorxiv.org/content/early/2016/05/21/054676 (2016).

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Authors
Gasperini, M., Starita, L., & Shendure, J.
Affiliations
  • University of Washington (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Shendure, Jay
Venue
Nature Protocols
Published
2016-09-01
Volume
11
Issue
10
Pages
1782-1787
ISSN
  • 1750-2799 (ISSN-L)
  • 1754-2189
OpenAlex
W2512645103
Cited by
160
References
84
Citations by year
2026: 12 · 2025: 19 · 2024: 28 · 2023: 17 · 2022: 10 · 2021: 15 · 2020: 13 · 2019: 17 · 2018: 15 · 2017: 13 · 2016: 1
FWCI
12.39
Type
journal article
Language
en
Open access
Locations
  • Nature Protocols (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Human Genome Research Institute (DP1HG007811, UM1HG009408)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
genetic variants, variant effect prediction, saturation mutagenesis, regulatory elements, protein variants, sequence-function relationships, functional genomics
MeSH terms
Animals, Genotype, Humans, Models, Molecular, Phenotype, Proteins, Genetic Variation, Mutagenesis, Genomics, High-Throughput Nucleotide Sequencing

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