Evidence map›Paper›PMID 41131366›Full record

ArticleNature methods2025

PHLOWER leverages single-cell multimodal data to infer complex, multi-branching cell differentiation trajectories.

Mingbo Cheng, Jitske Jansen, Katharina C Reimer, Vincent P Grande, James S Nagai, Zhijian Li, Paul Kießling, Martin Grasshoff, Christoph Kuppe, Michael T Schaub and 2 more

Abstract read
In one paragraph

Article in Nature methods, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. 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

12 authors.

Mingbo Cheng *Institute for Computational Genomics, RWTH Aachen University, Aachen, Germany.ORCID http://orcid.org/0000-0003-3938-0461
Jitske Jansen *Institute for Experimental Internal Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany.
Katharina C ReimerInstitute for Experimental Internal Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany.ORCID http://orcid.org/0000-0002-7118-9133
Vincent P GrandeDepartment of Computer Science, RWTH Aachen University, Aachen, Germany.
James S NagaiInstitute for Computational Genomics, RWTH Aachen University, Aachen, Germany.ORCID http://orcid.org/0000-0002-7655-7206
Zhijian LiGene Regulation Observatory, The Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-1523-1333
Paul KießlingInstitute for Experimental Internal Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany.ORCID http://orcid.org/0000-0002-9794-9532
Martin GrasshoffInstitute for Computational Genomics, RWTH Aachen University, Aachen, Germany.
Christoph KuppeInstitute for Experimental Internal Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany.ORCID http://orcid.org/0000-0003-4597-9833
Michael T SchaubCenter for Computational Life Sciences, RWTH Aachen University, Aachen, Germany.ORCID http://orcid.org/0000-0003-2426-6404
Rafael KramannCenter for Computational Life Sciences, RWTH Aachen University, Aachen, Germany. rkramann@ukaachen.de.ORCID http://orcid.org/0000-0003-4048-6351
Ivan G CostaInstitute for Computational Genomics, RWTH Aachen University, Aachen, Germany. ivan.costa@rwth-aachen.de.ORCID http://orcid.org/0000-0003-2890-8697

Funding

Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) Curefib, FibromapBundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) Fibromap, Curefib, Graphs4PatientBundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) Graphs4PatientsDeutsche Forschungsgemeinschaft (German Research Foundation) 388802535, 445703531, 417911533Deutsche Forschungsgemeinschaft (German Research Foundation) 4288578857858,445703531, SFBTRR219 322900939Deutsche Forschungsgemeinschaft (German Research Foundation) EN-459969915Deutsche Forschungsgemeinschaft (German Research Foundation) Research Training Group 2236 UnRAVeLEC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) ERC-COG 101043403EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) ERC-StG-101039827EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) ERC-StG-101040726
6 · The paper itself

Abstract

Computational trajectory analysis is a key computational task for inferring differentiation trees from this single-cell data. An open challenge is the prediction of complex and multi-branching trees from multimodal data. To address these challenges, we present PHLOWER (decomposition of the Hodge Laplacian for inferring trajectories from flows of cell differentiation), which leverages the harmonic component of the Hodge decomposition on simplicial complexes to infer trajectory embeddings from single-cell multimodal data. These natural representations of cell differentiation facilitate the estimation of their underlying differentiation trees. We evaluate PHLOWER through benchmarking with multi-branching differentiation trees and using kidney organoid multimodal and spatial single-cell data. These demonstrate the power of PHLOWER in both the inference of complex trees and the identification of transcription factors regulating off-target cells in kidney organoids. Thus, PHLOWER enables inference of complex branching trajectories and prediction of transcriptional regulators by leveraging multimodal data.

Indexed as

Cell DifferentiationComputational BiologySingle-Cell AnalysisAlgorithmsAnimalsHumansKidneyMiceOrganoidsTranscription FactorsTranscription Factors

Identifiers

PMID41131366
PMCPMC12615267

What OpenQuestion holds

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Registered trials

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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.