Evidence map›Paper›PMID 38177723›Full record

ArticleNature computational science2023

Interpretable neural architecture search and transfer learning for understanding CRISPR-Cas9 off-target enzymatic reactions.

Zijun Zhang, Adam R Lamson, Michael Shelley, Olga Troyanskaya

Abstract read
PubMed Publisher
In one paragraph

Article in Nature computational science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
–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 synthesis or guideline pooled it.

  1. Pooled it
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  8. Gene Therapy Techniques and Delivery Methods (Review).Sovremennye tekhnologii v meditsine · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

Zijun Zhang *Division of Artificial Intelligence in Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID 0000-0003-2016-8014
Adam R Lamson *Center for Computational Biology, Flatiron Institute, New York City, NY, USA.ORCID 0000-0003-2616-2801
Michael ShelleyCenter for Computational Biology, Flatiron Institute, New York City, NY, USA. mshelley@flatironinstitute.org.ORCID 0000-0002-4835-0339
Olga TroyanskayaCenter for Computational Biology, Flatiron Institute, New York City, NY, USA. ogt@genomics.princeton.edu.ORCID 0000-0002-5676-5737

Funding

lntegration and Visualization of Diverse Biological DataR01GM071966 · NIGMS · PRINCETON UNIVERSITY · PI TROYANSKAYA, OLGA G · 2005 to 2022
$6.4M
Simons Foundation 395506U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R01GM071966
6 · The paper itself

Abstract

Finely tuned enzymatic pathways control cellular processes, and their dysregulation can lead to disease. Developing predictive and interpretable models for these pathways is challenging because of the complexity of the pathways and of the cellular and genomic contexts. Here we introduce Elektrum, a deep learning framework that addresses these challenges with data-driven and biophysically interpretable models for determining the kinetics of biochemical systems. First, it uses in vitro kinetic assays to rapidly hypothesize an ensemble of high-quality kinetically interpretable neural networks (KINNs) that predict reaction rates. It then employs a transfer learning step, where the KINNs are inserted as intermediary layers into deeper convolutional neural networks, fine-tuning the predictions for reaction-dependent in vivo outcomes. We apply Elektrum to predict CRISPR-Cas9 off-target editing probabilities and demonstrate that Elektrum achieves improved performance, regularizes neural network architectures and maintains physical interpretability.

Indexed as

CRISPR-Cas SystemsNeural Networks, ComputerGenomicsMachine LearningRNA, Guide, CRISPR-Cas SystemsRNA, Guide, CRISPR-Cas Systems

Identifiers

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.