Evidence map›Paper›PMID 39829748›Full record

ArticlebioRxiv : the preprint server for biology2025

Engineering of CRISPR-Cas PAM recognition using deep learning of vast evolutionary data.

Stephen Nayfach, Aadyot Bhatnagar, Andrey Novichkov, Gabriella O Estevam, Nahye Kim, Emily Hill, Jeffrey A Ruffolo, Rachel Silverstein, Joseph Gallagher, Benjamin Kleinstiver and 3 more

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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.

No citing paper in PubMed yet.

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.

Stephen NayfachProfluent Bio, Berkeley, CA, USA.ORCID 0000-0003-4625-4164
Aadyot BhatnagarProfluent Bio, Berkeley, CA, USA.
Andrey NovichkovProfluent Bio, Berkeley, CA, USA.
Gabriella O EstevamProfluent Bio, Berkeley, CA, USA.ORCID 0000-0002-9142-7805
Nahye KimCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Emily HillProfluent Bio, Berkeley, CA, USA.
Jeffrey A RuffoloProfluent Bio, Berkeley, CA, USA.ORCID 0000-0002-3385-9191
Rachel SilversteinCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0001-5724-2252
Joseph GallagherProfluent Bio, Berkeley, CA, USA.
Benjamin KleinstiverCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0002-5469-0655
Alexander J MeeskeProfluent Bio, Berkeley, CA, USA.ORCID 0000-0003-3878-531X
Peter CameronProfluent Bio, Berkeley, CA, USA.
Ali MadaniProfluent Bio, Berkeley, CA, USA.ORCID 0000-0002-3092-1295

Funding

PROJECT 4: Somatic evolution of the hematopoietic system in cardiovascular diseaseP01HL142494 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Filip K Swirski · 2019 to 2026
$19.5M
Scalable Development of Custom Genome Editing TechnologiesDP2CA281401 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI KLEINSTIVER, BENJAMIN PETER · 2022 to 2025
$2.5M
NCI NIH HHS DP2 CA281401NHLBI NIH HHS P01 HL142494
6 · The paper itself

Abstract

CRISPR-Cas enzymes must recognize a protospacer-adjacent motif (PAM) to edit a genomic site, significantly limiting the range of targetable sequences in a genome. Machine learning-based protein engineering provides a powerful solution to efficiently generate Cas protein variants tailored to recognize specific PAMs. Here, we present Protein2PAM, an evolution-informed deep learning model trained on a dataset of over 45,000 CRISPR-Cas PAMs. Protein2PAM rapidly and accurately predicts PAM specificity directly from Cas proteins across Type I, II, and V CRISPR-Cas systems. Using

Indexed as

CRISPR-Casdeep learninggenome editingprotein design

Identifiers

PMID39829748
PMCPMC11741284

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.