DIRECTEUR : transcriptome-based prediction of small molecules that replace transcription factors for direct cell conversion
© The Author(s) 2024. Published by Oxford University Press..
MOTIVATION: Direct reprogramming (DR) is a process that directly converts somatic cells to target cells. Although DR via small molecules is safer than using transcription factors (TFs) in terms of avoidance of tumorigenic risk, the determination of DR-inducing small molecules is challenging.
RESULTS: Here we present a novel in silico method, DIRECTEUR, to predict small molecules that replace TFs for DR. We extracted DR-characteristic genes using transcriptome profiles of cells in which DR was induced by TFs, and performed a variant of simulated annealing to explore small molecule combinations with similar gene expression patterns with DR-inducing TFs. We applied DIRECTEUR to predicting combinations of small molecules that convert fibroblasts into neurons or cardiomyocytes, and were able to reproduce experimentally verified and functionally related molecules inducing the corresponding conversions. The proposed method is expected to be useful for practical applications in regenerative medicine.
AVAILABILITY AND IMPLEMENTATION: The code and data are available at the following link: https://github.com/HamanoLaboratory/DIRECTEUR.git.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:40 |
|---|---|
| Enthalten in: |
Bioinformatics (Oxford, England) - 40(2024), 2 vom: 01. Feb. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Hamano, Momoko [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Journal Article |
|---|
| Anmerkungen: |
Date Completed 14.02.2024 Date Revised 28.02.2024 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1093/bioinformatics/btae048 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM367641240 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM367641240 | ||
| 003 | DE-627 | ||
| 005 | 20240229234844.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240126s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1093/bioinformatics/btae048 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1311.xml |
| 035 | |a (DE-627)NLM367641240 | ||
| 035 | |a (NLM)38273708 | ||
| 035 | |a (PII)btae048 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Hamano, Momoko |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a DIRECTEUR |b transcriptome-based prediction of small molecules that replace transcription factors for direct cell conversion |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 14.02.2024 | ||
| 500 | |a Date Revised 28.02.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2024. Published by Oxford University Press. | ||
| 520 | |a MOTIVATION: Direct reprogramming (DR) is a process that directly converts somatic cells to target cells. Although DR via small molecules is safer than using transcription factors (TFs) in terms of avoidance of tumorigenic risk, the determination of DR-inducing small molecules is challenging | ||
| 520 | |a RESULTS: Here we present a novel in silico method, DIRECTEUR, to predict small molecules that replace TFs for DR. We extracted DR-characteristic genes using transcriptome profiles of cells in which DR was induced by TFs, and performed a variant of simulated annealing to explore small molecule combinations with similar gene expression patterns with DR-inducing TFs. We applied DIRECTEUR to predicting combinations of small molecules that convert fibroblasts into neurons or cardiomyocytes, and were able to reproduce experimentally verified and functionally related molecules inducing the corresponding conversions. The proposed method is expected to be useful for practical applications in regenerative medicine | ||
| 520 | |a AVAILABILITY AND IMPLEMENTATION: The code and data are available at the following link: https://github.com/HamanoLaboratory/DIRECTEUR.git | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 700 | 1 | |a Nakamura, Toru |e verfasserin |4 aut | |
| 700 | 1 | |a Ito, Ryoku |e verfasserin |4 aut | |
| 700 | 1 | |a Shimada, Yuki |e verfasserin |4 aut | |
| 700 | 1 | |a Iwata, Michio |e verfasserin |4 aut | |
| 700 | 1 | |a Takeshita, Jun-Ichi |e verfasserin |4 aut | |
| 700 | 1 | |a Eguchi, Ryohei |e verfasserin |4 aut | |
| 700 | 1 | |a Yamanishi, Yoshihiro |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Bioinformatics (Oxford, England) |d 1998 |g 40(2024), 2 vom: 01. Feb. |w (DE-627)NLM094620342 |x 1367-4811 |7 nnns |
| 773 | 1 | 8 | |g volume:40 |g year:2024 |g number:2 |g day:01 |g month:02 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1093/bioinformatics/btae048 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 40 |j 2024 |e 2 |b 01 |c 02 | ||