Evidence map›Paper›PMID 35483740›Full record

ArticleGenes & development2022

Functional dissection of human mitotic genes using CRISPR-Cas9 tiling screens.

Jacob A Herman, Sonali Arora, Lucas Carter, Jun Zhu, Sue Biggins, Patrick J Paddison

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Zombies Never Die: The Double Life Bub1 Lives in Mitosis.Frontiers in cell and developmental biology · 2022
    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

6 authors at 3 institutions in 1 country.

Jacob A HermanHoward Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Sonali AroraHuman Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Lucas CarterHuman Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Jun ZhuDepartment of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
Sue BigginsHoward Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Patrick J PaddisonHuman Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Fred Hutch Cancer Center · USHoward Hughes Medical Institute · USIcahn School of Medicine at Mount Sinai · US

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4M
Regulation of Chromosome SegregationR01GM064386 · NIGMS · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BIGGINS, SUSAN · 2002 to 2022
$7.2M
Defining cellular states of quiescence in human brain tumorsR01NS119650 · NINDS · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PADDISON, PATRICK · 2021 to 2025
$2.6M
MYC-dependent loss of splicing fidelity in Glioblastoma multiformeR01CA190957 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PADDISON, PATRICK · 2015 to 2019
$2.2M
NCI NIH HHS P30 CA015704NCI NIH HHS R01 CA190957NIGMS NIH HHS R01 GM064386NINDS NIH HHS R01 NS119650
6 · The paper itself

Abstract

The identity of human protein-coding genes is well known, yet our in-depth knowledge of their molecular functions and domain architecture remains limited by shortcomings in homology-based predictions and experimental approaches focused on whole-gene depletion. To bridge this knowledge gap, we developed a method that leverages CRISPR-Cas9-induced mutations across protein-coding genes for the a priori identification of functional regions at the sequence level. As a test case, we applied this method to 48 human mitotic genes, revealing hundreds of regions required for cell proliferation, including domains that were experimentally characterized, ones that were predicted based on homology, and novel ones. We validated screen outcomes for 15 regions, including amino acids 387-402 of Mad1, which were previously uncharacterized but contribute to Mad1 kinetochore localization and chromosome segregation fidelity. Altogether, we demonstrate that CRISPR-Cas9-based tiling mutagenesis identifies key functional domains in protein-coding genes de novo, which elucidates separation of function mutants and allows functional annotation across the human proteome.

Indexed as

CRISPR-Cas SystemsHumansMutagenesisCRISPR–Cas9functional genomicshuman genomehuman proteomekinetochoreMad1MAD1L1mitosisspindle assembly checkpoint

Identifiers

PMID35483740
PMCPMC9067404
OpenAlexW4225133232

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.