Evidence map›Paper›PMID 35576146›Full record

ArticleeLife2022

Machine learning sequence prioritization for cell type-specific enhancer design.

Alyssa J Lawler, Easwaran Ramamurthy, Ashley R Brown, Naomi Shin, Yeonju Kim, Noelle Toong, Irene M Kaplow, Morgan Wirthlin, Xiaoyu Zhang, BaDoi N Phan and 8 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.4field-weighted citation impact, top 10% of its field
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

20 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Article
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  4. Context-dependent regulatory variants in Alzheimer's disease.bioRxiv : the preprint server for biology · 2025
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  6. Combining Machine Learning and Multiplexed,bioRxiv : the preprint server for biology · 2025
    Article
  7. Article
  8. AnFrontiers in genetics · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Machine-guided design of synthetic cell type-specificbioRxiv : the preprint server for biology · 2023
    Article
  16. Review
  17. Article
  18. Molecular therapy. Methods & clinical development · 2023
    Article
  19. Review
  20. Article
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

18 authors at 2 institutions in 2 countries.

Alyssa J LawlerComputational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, United States.ORCID 0000-0002-2151-5164
Easwaran RamamurthyComputational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, United States.ORCID 0000-0002-2439-0600
Ashley R BrownComputational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, United States.ORCID 0000-0002-3091-3930
Naomi ShinComputational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, United States.
Yeonju KimComputational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, United States.
Noelle ToongComputational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, United States.
Irene M KaplowComputational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, United States.ORCID 0000-0002-8924-8269
Morgan WirthlinComputational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, United States.ORCID 0000-0001-7967-7070
Xiaoyu ZhangComputational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, United States.
BaDoi N PhanComputational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, United States.ORCID 0000-0001-6331-5980
Grant A FoxComputational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, United States.
Kirsten WadeDepartment of Psychiatry, Translational Neuroscience Program, University of Pittsburgh, Pittsburgh, United States.
Jing HeDepartment of Neurobiology, University of Pittsburgh, Pittsburgh, United States.ORCID 0000-0001-9034-8390
Bilge Esin OzturkDepartment of Ophthalmology, University of Pittsburgh, Pittsburgh, United States.ORCID 0000-0001-5117-077X
Leah C ByrneDepartment of Neurobiology, University of Pittsburgh, Pittsburgh, United States.ORCID 0000-0002-3229-4993
William R StaufferDepartment of Neurobiology, University of Pittsburgh, Pittsburgh, United States.ORCID 0000-0003-1031-8824
Kenneth N FishDepartment of Psychiatry, Translational Neuroscience Program, University of Pittsburgh, Pittsburgh, United States.ORCID 0000-0003-1774-3815
Andreas R PfenningComputational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, United States.ORCID 0000-0002-3447-9801
Neuroscience Institute · ITUniversity of Pittsburgh · US

Funding

A Massive Library of AAVs to Target Transcriptionally-Defined Primate Cell TypesUG3MH120094 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI STAUFFER, WILLIAM RICHARD · 2019 to 2021
$5.8M
Interpreting the regulatory mechanisms underlying the predisposition to substance use disordersDP1DA046585 · NIDA · CARNEGIE-MELLON UNIVERSITY · PI PFENNING, ANDREAS ROBERT · 2018 to 2022
$2.4M
Deciphering the GABA neuron alterations in schizophreniaR01MH119701 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FISH, KENNETH N · 2019 to 2023
$2.2M
Chandelier cell inputs to pyramidal neurons in schizophrenia and developmentR01MH096985 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FISH, KENNETH N · 2012 to 2015
$1.2M
Integrating primate-rodent cell types and epigenomics to identify conservation in substance addictionF30DA053020 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PHAN, BADOI NGUYEN · 2021 to 2024
$204k
NIDA NIH HHS DP1 DA046585NIDA NIH HHS F30 DA053020NIMH NIH HHS R01 MH096985NIMH NIH HHS R01 MH119701NIMH NIH HHS UG3 MH120094
6 · The paper itself

Abstract

Recent discoveries of extreme cellular diversity in the brain warrant rapid development of technologies to access specific cell populations within heterogeneous tissue. Available approaches for engineering-targeted technologies for new neuron subtypes are low yield, involving intensive transgenic strain or virus screening. Here, we present Specific Nuclear-Anchored Independent Labeling (SNAIL), an improved virus-based strategy for cell labeling and nuclear isolation from heterogeneous tissue. SNAIL works by leveraging machine learning and other computational approaches to identify DNA sequence features that confer cell type-specific gene activation and then make a probe that drives an affinity purification-compatible reporter gene. As a proof of concept, we designed and validated two novel SNAIL probes that target parvalbumin-expressing (PV+) neurons. Nuclear isolation using SNAIL in wild-type mice is sufficient to capture characteristic open chromatin features of PV+ neurons in the cortex, striatum, and external globus pallidus. The SNAIL framework also has high utility for multispecies cell probe engineering; expression from a mouse PV+ SNAIL enhancer sequence was enriched in PV+ neurons of the macaque cortex. Expansion of this technology has broad applications in cell type-specific observation, manipulation, and therapeutics across species and disease models.

Indexed as

Enhancer Elements, GeneticMachine LearningNeuronsSequence Analysis, DNAAnimalsCerebral CortexComputational BiologyGlobus PallidusMiceParvalbuminsParvalbuminscell type-specific enhancersgeneticsgenomicsmachine learningmouseneuron subtype isolationneuroscienceparvalbumin neuronsrhesus macaque

Identifiers

PMID35576146
PMCPMC9110026
OpenAlexW4280537207

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.