SCENIC: Single-cell Regulatory Network Inference and Clustering

Overview

Journal Nat Methods

Specialties Biomedical Engineering
Pathology

Date 2017 Oct 10

PMID 28991892

Citations 2308

Authors

Sara Aibar

Carmen Bravo Gonzalez-Blas

Thomas Moerman

Van Anh Huynh-Thu

Hana Imrichova

Gert Hulselmans

Florian Rambow

Jean-Christophe Marine

Pierre Geurts

Jan Aerts

Joost van den Oord

Zeynep Kalender Atak

Jasper Wouters

Stein Aerts

Affiliations

Soon will be listed here.

Abstract

We present SCENIC, a computational method for simultaneous gene regulatory network reconstruction and cell-state identification from single-cell RNA-seq data (http://scenic.aertslab.org). On a compendium of single-cell data from tumors and brain, we demonstrate that cis-regulatory analysis can be exploited to guide the identification of transcription factors and cell states. SCENIC provides critical biological insights into the mechanisms driving cellular heterogeneity.

Citing Articles

Combination therapy with Chicoric acid and PD-1/PD-L1 blockade improves the immunotherapy response in patient-derived ovarian cancer xenograft model.

Lan H, Zhu J, Hou H, Zhang C, Huo X, Zhang Y Cell Commun Signal. 2025; 23(1):137.

PMID: 40087780 DOI: 10.1186/s12964-025-02146-7.

Integrated analysis of single-cell and bulk transcriptomes uncovers clinically relevant molecular subtypes in human prostate cancer.

Ding T, He L, Lin G, Xu L, Zhu Y, Wang X Chin J Cancer Res. 2025; 37(1):90-114.

PMID: 40078560 PMC: 11893346. DOI: 10.21147/j.issn.1000-9604.2025.01.07.

Single-Cell Transcriptional Profiling Reveals Cell Type-Specific Sex-Dependent Molecular Patterns of Schizophrenia.

Zhou R, Zhang T, Sun B Int J Mol Sci. 2025; 26(5).

PMID: 40076849 PMC: 11900070. DOI: 10.3390/ijms26052227.

Single-Cell Sequencing: Genomic and Transcriptomic Approaches in Cancer Cell Biology.

Ortega-Batista A, Jaen-Alvarado Y, Moreno-Labrador D, Gomez N, Garcia G, Guerrero E Int J Mol Sci. 2025; 26(5).

PMID: 40076700 PMC: 11901077. DOI: 10.3390/ijms26052074.

The Emerging Role of CD8 T Cells in Shaping Treatment Outcomes of Patients with MDS and AML.

Tasis A, Spyropoulos T, Mitroulis I Cancers (Basel). 2025; 17(5).

PMID: 40075597 PMC: 11898900. DOI: 10.3390/cancers17050749.

References

Denny S, Yang D, Chuang C, Brady J, Lim J, Gruner B . Nfib Promotes Metastasis through a Widespread Increase in Chromatin Accessibility. Cell. 2016; 166(2):328-342. PMC: 5004630. DOI: 10.1016/j.cell.2016.05.052. View

Janky R, Verfaillie A, Imrichova H, Van de Sande B, Standaert L, Christiaens V . iRegulon: from a gene list to a gene regulatory network using large motif and track collections. PLoS Comput Biol. 2014; 10(7):e1003731. PMC: 4109854. DOI: 10.1371/journal.pcbi.1003731. View

Aerts S, Quan X, Claeys A, Naval Sanchez M, Tate P, Yan J . Robust target gene discovery through transcriptome perturbations and genome-wide enhancer predictions in Drosophila uncovers a regulatory basis for sensory specification. PLoS Biol. 2010; 8(7):e1000435. PMC: 2910651. DOI: 10.1371/journal.pbio.1000435. View

Tirosh I, Venteicher A, Hebert C, Escalante L, Patel A, Yizhak K . Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma. Nature. 2016; 539(7628):309-313. PMC: 5465819. DOI: 10.1038/nature20123. View

Warde-Farley D, Donaldson S, Comes O, Zuberi K, Badrawi R, Chao P . The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res. 2010; 38(Web Server issue):W214-20. PMC: 2896186. DOI: 10.1093/nar/gkq537. View

Lun A, McCarthy D, Marioni J . A step-by-step workflow for low-level analysis of single-cell RNA-seq data with Bioconductor. F1000Res. 2016; 5:2122. PMC: 5112579. DOI: 10.12688/f1000research.9501.2. View

Forbes S, Beare D, Boutselakis H, Bamford S, Bindal N, Tate J . COSMIC: somatic cancer genetics at high-resolution. Nucleic Acids Res. 2016; 45(D1):D777-D783. PMC: 5210583. DOI: 10.1093/nar/gkw1121. View

Marbach D, Costello J, Kuffner R, Vega N, Prill R, Camacho D . Wisdom of crowds for robust gene network inference. Nat Methods. 2012; 9(8):796-804. PMC: 3512113. DOI: 10.1038/nmeth.2016. View

Alizadeh A, Aranda V, Bardelli A, Blanpain C, Bock C, Borowski C . Toward understanding and exploiting tumor heterogeneity. Nat Med. 2015; 21(8):846-53. PMC: 4785013. DOI: 10.1038/nm.3915. View

10.

Pina C, Teles J, Fugazza C, May G, Wang D, Guo Y . Single-Cell Network Analysis Identifies DDIT3 as a Nodal Lineage Regulator in Hematopoiesis. Cell Rep. 2015; 11(10):1503-10. PMC: 4528262. DOI: 10.1016/j.celrep.2015.05.016. View

11.

Tirosh I, Izar B, Prakadan S, Wadsworth 2nd M, Treacy D, Trombetta J . Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science. 2016; 352(6282):189-96. PMC: 4944528. DOI: 10.1126/science.aad0501. View

12.

Guo M, Wang H, Potter S, Whitsett J, Xu Y . SINCERA: A Pipeline for Single-Cell RNA-Seq Profiling Analysis. PLoS Comput Biol. 2015; 11(11):e1004575. PMC: 4658017. DOI: 10.1371/journal.pcbi.1004575. View

13.

Linnarsson S, Teichmann S . Single-cell genomics: coming of age. Genome Biol. 2016; 17:97. PMC: 4862185. DOI: 10.1186/s13059-016-0960-x. View

14.

Macosko E, Basu A, Satija R, Nemesh J, Shekhar K, Goldman M . Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets. Cell. 2015; 161(5):1202-1214. PMC: 4481139. DOI: 10.1016/j.cell.2015.05.002. View

15.

Johnson W, Li C, Rabinovic A . Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics. 2006; 8(1):118-27. DOI: 10.1093/biostatistics/kxj037. View

16.

Zeisel A, Munoz-Manchado A, Codeluppi S, Lonnerberg P, La Manno G, Jureus A . Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science. 2015; 347(6226):1138-42. DOI: 10.1126/science.aaa1934. View

17.

Chang C, Pasolli H, Giannopoulou E, Guasch G, Gronostajski R, Elemento O . NFIB is a governor of epithelial-melanocyte stem cell behaviour in a shared niche. Nature. 2013; 495(7439):98-102. PMC: 3635831. DOI: 10.1038/nature11847. View

18.

Edgar R, Domrachev M, Lash A . Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 2001; 30(1):207-10. PMC: 99122. DOI: 10.1093/nar/30.1.207. View

19.

Kiselev V, Kirschner K, Schaub M, Andrews T, Yiu A, Chandra T . SC3: consensus clustering of single-cell RNA-seq data. Nat Methods. 2017; 14(5):483-486. PMC: 5410170. DOI: 10.1038/nmeth.4236. View

20.

Perotti V, Baldassari P, Molla A, Vegetti C, Bersani I, Maurichi A . NFATc2 is an intrinsic regulator of melanoma dedifferentiation. Oncogene. 2015; 35(22):2862-72. DOI: 10.1038/onc.2015.355. View