Evidence map›Paper›PMID 38293072›Full record

ArticlebioRxiv : the preprint server for biology2024

Genome-scale analysis of interactions between genetic perturbations and natural variation.

Joseph J Hale, Takeshi Matsui, Ilan Goldstein, Martin N Mullis, Kevin R Roy, Chris Ne Ville, Darach Miller, Charley Wang, Trevor Reynolds, Lars M Steinmetz and 2 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed, 2 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 2 countries.

Joseph J HaleMolecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.ORCID 0009-0001-9130-5269
Takeshi MatsuiSLAC National Accelerator Laboratory, Menlo Park, CA, 94025, USA.ORCID 0000-0002-5561-8751
Ilan GoldsteinMolecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Martin N MullisMolecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Kevin R RoyStanford Genome Technology Center, Stanford University, Palo Alto, California, USA.ORCID 0000-0001-8799-6207
Chris Ne VilleMolecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Darach MillerSLAC National Accelerator Laboratory, Menlo Park, CA, 94025, USA.
Charley WangMolecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Trevor ReynoldsMolecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Lars M SteinmetzStanford Genome Technology Center, Stanford University, Palo Alto, California, USA.ORCID 0000-0002-3962-2865
Sasha F LevySLAC National Accelerator Laboratory, Menlo Park, CA, 94025, USA.ORCID 0000-0002-0923-1636
Ian M EhrenreichMolecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
University of Southern California · USSLAC National Accelerator Laboratory · USEuropean Molecular Biology Laboratory · DEStanford University · US

Funding

Characterizing the complex underpinnings of genetic background effectsR35GM130381 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Ian Michael Ehrenreich · 2019 to 2026
$3.3M
Comparative Functional Genomics of YeastR01HG010378 · NHGRI · STANFORD UNIVERSITY · PI DUNHAM, MAITREYA J, SHERLOCK, GAVIN J · 2019 to 2022
$2.3M
PPiSeq: High-Throughput Protein-Protein Interaction SequencingR01AI164530 · NIAID · STANFORD UNIVERSITY · PI SHERLOCK, GAVIN J · 2021 to 2024
$1.7M
NHGRI NIH HHS R01 HG010378NIAID NIH HHS R01 AI164530NIGMS NIH HHS R35 GM130381
6 · The paper itself

Abstract

Interactions between genetic perturbations and segregating loci can cause perturbations to show different phenotypic effects across genetically distinct individuals. To study these interactions on a genome scale in many individuals, we used combinatorial DNA barcode sequencing to measure the fitness effects of 7,700 CRISPRi perturbations targeting 1,712 distinct genes in 169 yeast cross progeny (or segregants). We identified 460 genes whose perturbation has different effects across segregants. Several factors caused perturbations to show variable effects, including baseline segregant fitness, the mean effect of a perturbation across segregants, and interacting loci. We mapped 234 interacting loci and found four hub loci that interact with many different perturbations. Perturbations that interact with a given hub exhibit similar epistatic relationships with the hub and show enrichment for cellular processes that may mediate these interactions. These results suggest that an individual's response to perturbations is shaped by a network of perturbation-locus interactions that cannot be measured by approaches that examine perturbations or natural variation alone.

Identifiers

PMID38293072
PMCPMC10827069
OpenAlexW4375866490

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.