Evidence map›Paper›PMID 37154091›Full record

ArticleMolecular systems biology2023

Predicting cellular responses to complex perturbations in high-throughput screens.

Mohammad Lotfollahi, Anna Klimovskaia Susmelj, Carlo De Donno, Leon Hetzel, Yuge Ji, Ignacio L Ibarra, Sanjay R Srivatsan, Mohsen Naghipourfar, Riza M Daza, Beth Martin and 9 more

Abstract read
In one paragraph

Article in Molecular systems biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers.

0numbers the graph read from it
0cells of the map it votes in
159citing 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

159 citing papers in PubMed.

  1. Review
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  3. Single-cell RNA profiling suggests goflikicept-mediated immune modulation in idiopathic recurrent pericarditis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
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99 more citing papers are in PubMed but not listed here.

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

19 authors.

Mohammad Lotfollahi *Helmholtz Center Munich - German Research Center for Environmental Health, Institute of Computational Biology, Munich, Germany.
Anna Klimovskaia Susmelj *Meta AI, Paris, France.ORCID 0000-0002-1057-6690
Carlo De Donno *Helmholtz Center Munich - German Research Center for Environmental Health, Institute of Computational Biology, Munich, Germany.ORCID 0000-0002-9553-0121
Leon HetzelHelmholtz Center Munich - German Research Center for Environmental Health, Institute of Computational Biology, Munich, Germany.ORCID 0000-0002-4823-9729
Yuge JiHelmholtz Center Munich - German Research Center for Environmental Health, Institute of Computational Biology, Munich, Germany.
Ignacio L IbarraHelmholtz Center Munich - German Research Center for Environmental Health, Institute of Computational Biology, Munich, Germany.ORCID 0000-0002-0582-002X
Sanjay R SrivatsanDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Mohsen NaghipourfarDepartment of Bioengineering, University of California, Berkeley, CA, USA.
Riza M DazaDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID 0000-0003-1635-8675
Beth MartinDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Jay ShendureDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Jose L McFaline-FigueroaDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.ORCID 0000-0003-4387-1511
Pierre BoyeauDepartment of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA, USA.
F Alexander WolfHelmholtz Center Munich - German Research Center for Environmental Health, Institute of Computational Biology, Munich, Germany.
Nafissa YakubovaMeta AI, Paris, France.
Stephan GünnemannDepartment of Computer Science, Technical University of Munich, Munich, Germany.
Cole TrapnellDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
David Lopez-PazWellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK.
Fabian J TheisHelmholtz Center Munich - German Research Center for Environmental Health, Institute of Computational Biology, Munich, Germany.ORCID 0000-0002-2419-1943

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recent advances in multiplexed single-cell transcriptomics experiments facilitate the high-throughput study of drug and genetic perturbations. However, an exhaustive exploration of the combinatorial perturbation space is experimentally unfeasible. Therefore, computational methods are needed to predict, interpret, and prioritize perturbations. Here, we present the compositional perturbation autoencoder (CPA), which combines the interpretability of linear models with the flexibility of deep-learning approaches for single-cell response modeling. CPA learns to in silico predict transcriptional perturbation response at the single-cell level for unseen dosages, cell types, time points, and species. Using newly generated single-cell drug combination data, we validate that CPA can predict unseen drug combinations while outperforming baseline models. Additionally, the architecture's modularity enables incorporating the chemical representation of the drugs, allowing the prediction of cellular response to completely unseen drugs. Furthermore, CPA is also applicable to genetic combinatorial screens. We demonstrate this by imputing in silico 5,329 missing combinations (97.6% of all possibilities) in a single-cell Perturb-seq experiment with diverse genetic interactions. We envision CPA will facilitate efficient experimental design and hypothesis generation by enabling in silico response prediction at the single-cell level and thus accelerate therapeutic applications using single-cell technologies.

Indexed as

Computational BiologyGene Expression ProfilingHigh-Throughput Screening AssaysSingle-Cell Gene Expression Analysisgenerative modelinghigh-throughput screeningmachine learningperturbation predictionsingle-cell transcriptomics

Identifiers

PMID37154091
PMCPMC10258562

What OpenQuestion holds

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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.