Evidence map›Paper›PMID 29786095›Full record

ArticleNature biotechnology2018

High-throughput creation and functional profiling of DNA sequence variant libraries using CRISPR-Cas9 in yeast.

Xiaoge Guo, Alejandro Chavez, Angela Tung, Yingleong Chan, Christian Kaas, Yi Yin, Ryan Cecchi, Santiago Lopez Garnier, Eric D Kelsic, Max Schubert and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Nature biotechnology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
5.7field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

50 citing papers in PubMed, 105 citations in OpenAlex.

  1. Identification and Characterization of Microproteins/ MicroORFs.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Comprehensive deletion scan of anti-CRISPR AcrIIA4 reveals essential and dispensable domains for Cas9 inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Dissecting quantitative trait nucleotides by saturation genome editing.bioRxiv : the preprint server for biology · 2024
    Article
  12. Article
  13. Review
  14. Review
  15. ACS synthetic biology · 2023
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 2 countries.

Xiaoge GuoWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts, USA.
Alejandro ChavezWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts, USA.
Angela TungWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts, USA.
Yingleong ChanWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts, USA.
Christian KaasWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts, USA.
Yi YinDepartment of Genome Sciences, University of Washington, Seattle, Washington, USA.
Ryan CecchiWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts, USA.
Santiago Lopez GarnierWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts, USA.ORCID 0000-0001-7576-2438
Eric D KelsicWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts, USA.ORCID 0000-0002-5331-5204
Max SchubertWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts, USA.
James E DiCarloWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts, USA.
James J CollinsWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts, USA.
George M ChurchWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts, USA.ORCID 0000-0003-3535-2076
Harvard University · USBroad Institute · US

Funding

Causal Transcriptional Consequences of Human Genetic VariationP50HG005550 · NHGRI · HARVARD MEDICAL SCHOOL · PI CHURCH, GEORGE M · 2010 to 2014
$19.0M
MOLECULAR IMMUNOLOGY AND TUMOR BIOLOGYT32CA009216 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI David Michael Langenau · 1985 to 2026
$10.6M
Center for Genomically Engineered OrgansRM1HG008525 · NHGRI · HARVARD MEDICAL SCHOOL · PI CHURCH, GEORGE M · 2015 to 2019
$10.2M
NCI NIH HHS T32 CA009216NHGRI NIH HHS P50 HG005550NHGRI NIH HHS RM1 HG008525
6 · The paper itself

Abstract

Construction and characterization of large genetic variant libraries is essential for understanding genome function, but remains challenging. Here, we introduce a Cas9-based approach for generating pools of mutants with defined genetic alterations (deletions, substitutions, and insertions) with an efficiency of 80-100% in yeast, along with methods for tracking their fitness en masse. We demonstrate the utility of our approach by characterizing the DNA helicase SGS1 with small tiling deletion mutants that span the length of the protein and a series of point mutations against highly conserved residues in the protein. In addition, we created a genome-wide library targeting 315 poorly characterized small open reading frames (smORFs, <100 amino acids in length) scattered throughout the yeast genome, and assessed which are vital for growth under various environmental conditions. Our strategy allows fundamental biological questions to be investigated in a high-throughput manner with precision.

Indexed as

Gene LibraryBase SequenceBiotechnologyConserved SequenceCRISPR-Cas SystemsDNA, FungalGenetic VariationHigh-Throughput Nucleotide SequencingOpen Reading FramesPoint MutationRecQ HelicasesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence DeletionDNA, FungalRecQ HelicasesSaccharomyces cerevisiae ProteinsSGS1 protein, S cerevisiae

Identifiers

PMID29786095
PMCPMC5990468
OpenAlexW2804704854

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.