Evidence map›Paper›PMID 40672188›Full record

ArticlebioRxiv : the preprint server for biology2025

Refate identifies chemical compounds to target trans-regulatory networks for cellular conversion.

Di Xiao, Sonu Sahadevan, Melissa M Mangala, Hani Jieun Kim, Anna Fredericks, Hao Huang, Raja Jothi, Patrick Tam, Anai Gonzalez-Cordero, Katherine G Zyner and 1 more

Abstract readPreprint
PubMed Full text at PMC Publisher
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

11 authors.

Di XiaoComputational Systems Biology Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia.
Sonu SahadevanComputational Systems Biology Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia.
Melissa M MangalaStem Cell Medicine Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia.
Hani Jieun KimComputational Systems Biology Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia.
Anna FredericksComputational Systems Biology Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia.
Hao HuangComputational Systems Biology Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia.
Raja JothiEpigenetics & RNA Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC 27709, USA.
Patrick TamEmbryology Research Unit, Children's Medical Research Institute, and School of Medical Sciences, The University of Sydney, Westmead, NSW 2145, Australia.
Anai Gonzalez-CorderoStem Cell Medicine Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia.
Katherine G ZynerComputational Systems Biology Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia.
Pengyi YangComputational Systems Biology Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia.

Funding

Gene regulatory elements, networks, and mechanismsZIAES102625 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI JOTHI, RAJA · 2009 to 2025
$27.4M
Intramural NIH HHS ZIA ES102625
6 · The paper itself

Abstract

Identifying chemical compounds that target trans-regulatory networks (TRNs) underlying molecular programs of cells for directed cellular conversion (i.e. differentiation, reprogramming, transdifferentiation, and dedifferentiation) is a key step towards advancing regenerative medicine. Recent innovations in single-cell omics technologies enabled high-resolution profiling of TRNs that govern cell identity and cell-fate decisions. Here, we introduce Refate, a computational framework that integrates large-scale multimodal single-cell atlas data to quantify cell propensity of genes, together with six drug databases, to identify chemical compounds that target TRNs for directed cellular conversion. The reconstructed TRNs, including protein-protein interactions and gene regulatory networks, alongside chemical compounds that drive the cellular conversion provide greater biological interpretability and improve efficiency and efficacy. We evaluated Refate by testing its ability to uncover known transcription factors and chemical compounds validated in experimental conversions of various cell types. Furthermore, we experimentally validated the attribute of several novel chemical compounds identified by Refate for enhancing the conversion of human embryonic stem cells to human cranial neural crest cells. Together, these findings demonstrate Refate as an effective tool for discovering chemical compounds that target TRNs to enable cellular conversion, advancing efforts towards regenerative medicine.

Identifiers

PMID40672188
PMCPMC12265640

What Socratic holds

Textmetadata
LicenceCC BY-NC
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 Socratic graph.