Evidence map›Paper›PMID 37078688›Full record

ArticleBriefings in bioinformatics2023

Decoding CRISPR-Cas PAM recognition with UniDesign.

Xiaoqiang Huang, Jun Zhou, Dongshan Yang, Jifeng Zhang, Xiaofeng Xia, Yuqing Eugene Chen, Jie Xu

Abstract read
In one paragraph

Article in Briefings in bioinformatics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Fully computational design of PAM-relaxedbioRxiv : the preprint server for biology · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. 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

7 authors.

Xiaoqiang HuangCenter for Advanced Models for Translational Sciences and Therapeutics, Department of Internal Medicine, University of Michigan Medical School, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.
Jun ZhouCenter for Advanced Models for Translational Sciences and Therapeutics, Department of Internal Medicine, University of Michigan Medical School, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.
Dongshan YangCenter for Advanced Models for Translational Sciences and Therapeutics, Department of Internal Medicine, University of Michigan Medical School, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.
Jifeng ZhangCenter for Advanced Models for Translational Sciences and Therapeutics, Department of Internal Medicine, University of Michigan Medical School, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.
Xiaofeng XiaResearch & Development, ATGC Inc., 100 E Lancaster Avenue, LIMR Building Lab 129, Wynnewood, PA 19096, USA.
Yuqing Eugene ChenCenter for Advanced Models for Translational Sciences and Therapeutics, Department of Internal Medicine, University of Michigan Medical School, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.
Jie XuCenter for Advanced Models for Translational Sciences and Therapeutics, Department of Internal Medicine, University of Michigan Medical School, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.

Funding

IDOL and dyslipidemia in cardiovascular diseasesR01HL147527 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHEN, YUQING EUGENE · 2019 to 2022
$3.1M
Development of gene editing based therapy for cardiovascular diseasesR01HL159900 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHEN, YUQING EUGENE, HAN, RENZHI · 2021 to 2024
$2.8M
Browning of perivascular adipose tissue protects against thoracic aortic aneurysmR01HL159871 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHEN, YUQING EUGENE · 2022 to 2025
$2.3M
Novel methods to improve nuclease mediated homologous recombination, Administrative supplR42GM122181 · NIGMS · ATGC, INC. · PI ZHANG, JIFENG · 2022 to 2023
$2.1M
Structure-based computational engineering of saCas9 PAM requirementR41GM149016 · NIGMS · ATGC, INC. · PI HUANG, XIAOQIANG, XIA, XIAOFENG · 2023 to 2023
$275k
Novel methods to improve nuclease mediated homologous recombinationR41GM122181 · NIGMS · ATGC, INC. · PI ZHANG, JIFENG · 2017 to 2017
$225k
NHLBI NIH HHS R01 HL147527NHLBI NIH HHS R01 HL159871NHLBI NIH HHS R01 HL159900NIGMS NIH HHS R41 GM122181NIGMS NIH HHS R41 GM149016NIGMS NIH HHS R42 GM122181
6 · The paper itself

Abstract

The critical first step in Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated (CRISPR-Cas) protein-mediated gene editing is recognizing a preferred protospacer adjacent motif (PAM) on target DNAs by the protein's PAM-interacting amino acids (PIAAs). Thus, accurate computational modeling of PAM recognition is useful in assisting CRISPR-Cas engineering to relax or tighten PAM requirements for subsequent applications. Here, we describe a universal computational protein design framework (UniDesign) for designing protein-nucleic acid interactions. As a proof of concept, we applied UniDesign to decode the PAM-PIAA interactions for eight Cas9 and two Cas12a proteins. We show that, given native PIAAs, the UniDesign-predicted PAMs are largely identical to the natural PAMs of all Cas proteins. In turn, given natural PAMs, the computationally redesigned PIAA residues largely recapitulated the native PIAAs (74% and 86% in terms of identity and similarity, respectively). These results demonstrate that UniDesign faithfully captures the mutual preference between natural PAMs and native PIAAs, suggesting it is a useful tool for engineering CRISPR-Cas and other nucleic acid-interacting proteins. UniDesign is open-sourced at https://github.com/tommyhuangthu/UniDesign.

Indexed as

CRISPR-Cas SystemsNucleic AcidsDNAGene EditingDNANucleic Acidscomputational protein designCRISPR–Casgene editingPAMUniDesign

Identifiers

PMID37078688
PMCPMC10199764

What OpenQuestion holds

Textmetadata
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.