Skip to main content

Inferring Gene Regulatory Networks and Predicting the Effect of Gene Perturbations via IQCELL

  • Protocol
  • First Online:
Embryo Models In Vitro

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2767))

  • 291 Accesses

Abstract

IQCELL is a platform that infers Boolean gene regulatory networks from single-cell RNA sequencing data. Boolean networks can be simulated under normal and perturbed conditions. In this chapter, we provide a detailed guideline for implementing IQCELL from a raw dataset. The steps include processing data, inferring informative genes, inferring gene regulatory network, and simulating the resulted network under normal and perturbed conditions.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Aibar S, González-Blas CB, Moerman T, Huynh-Thu VA, Imrichova H, Hulselmans G, Rambow F, Marine J-C, Geurts P, Aerts J, van den Oord J, Atak ZK, Wouters J, Aerts S (2017) SCENIC: single-cell regulatory network inference and clustering. Nat Methods 14:1083–1086. https://doi.org/10.1038/nmeth.4463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bass AJ, Robinson DG, Storey JD (2019) Determining sufficient sequencing depth in RNA-Seq differential expression studies. bioRxiv: 635623

    Google Scholar 

  3. Boveri T (1907) Zellen-Studien: Die Entwicklung dispermer Seeigel-Eier. G. Fischer

    Google Scholar 

  4. Britten RJ, Davidson EH (1969) Gene regulation for higher cells: a theory. Science 165:349–357

    Article  CAS  PubMed  Google Scholar 

  5. Davidson EH (2002) A genomic regulatory network for development. Science 295:1669–1678. https://doi.org/10.1126/science.1069883

    Article  CAS  PubMed  Google Scholar 

  6. Heydari T, Langley MA, Fisher CL, Aguilar-Hidalgo D, Shukla S, Yachie-Kinoshita A, Hughes M, M. McNagny K, Zandstra PW (2022) IQCELL: a platform for predicting the effect of gene perturbations on developmental trajectories using single-cell RNA-seq data. PLOS Comput Biol 18:e1009907. https://doi.org/10.1371/journal.pcbi.1009907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kathiriya IS, Rao KS, Iacono G, Devine WP, Blair AP, Hota SK, Lai MH, Garay BI, Thomas R, Gong HZ, Wasson LK, Goyal P, Sukonnik T, Hu KM, Akgun GA, Bernard LD, Akerberg BN, Gu F, Li K, Speir ML, Haeussler M, Pu WT, Stuart JM, Seidman CE, Seidman JG, Heyn H, Bruneau BG (2021) Modeling human TBX5 haploinsufficiency predicts regulatory networks for congenital heart disease. Dev Cell 56:292–309.e9. https://doi.org/10.1016/j.devcel.2020.11.020

  8. Lipsitz YY, Timmins NE, Zandstra PW (2016) Quality cell therapy manufacturing by design. Nat Biotechnol 34:393–400. https://doi.org/10.1038/nbt.3525

    Article  CAS  PubMed  Google Scholar 

  9. Longabaugh WJR, Zeng W, Zhang JA, Hosokawa H, Jansen CS, Li L, Romero-Wolf M, Liu P, Kueh HY, Mortazavi A, Rothenberg EV (2017) Bcl11b and combinatorial resolution of cell fate in the T-cell gene regulatory network. Proc Natl Acad Sci 114:5800–5807. https://doi.org/10.1073/pnas.1610617114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Morgan TH, others (1934) Embryology and genetics. Embryol Genet

    Google Scholar 

  11. Nestorowa S, Hamey FK, Pijuan Sala B, Diamanti E, Shepherd M, Laurenti E, Wilson NK, Kent DG, Göttgens B (2016) A single-cell resolution map of mouse hematopoietic stem and progenitor cell differentiation. Blood 128:e20–e31. https://doi.org/10.1182/blood-2016-05-716480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Peter IS, Davidson EH (2015) Genomic control process: development and evolution. Academic Press, San Diego

    Google Scholar 

  13. Peter IS, Faure E, Davidson EH (2012) Predictive computation of genomic logic processing functions in embryonic development. Proc Natl Acad Sci 109:16434–16442. https://doi.org/10.1073/pnas.1207852109

    Article  PubMed  PubMed Central  Google Scholar 

  14. Small S, Kraut R, Hoey T, Warrior R, Levine M (1991) Transcriptional regulation of a pair-rule stripe in Drosophila. Genes Dev 5:827–839

    Article  CAS  PubMed  Google Scholar 

  15. Street K, Risso D, Fletcher RB, Das D, Ngai J, Yosef N, Purdom E, Dudoit S (2018) Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics. BMC Genomics 19:477. https://doi.org/10.1186/s12864-018-4772-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676. https://doi.org/10.1016/j.cell.2006.07.024

    Article  CAS  PubMed  Google Scholar 

  17. Tewary M, Shakiba N, Zandstra PW (2018) Stem cell bioengineering: building from stem cell biology. Nat Rev Genet 19:595–614. https://doi.org/10.1038/s41576-018-0040-z

    Article  CAS  PubMed  Google Scholar 

  18. Van de Sande B, Flerin C, Davie K, De Waegeneer M, Hulselmans G, Aibar S, Seurinck R, Saelens W, Cannoodt R, Rouchon Q, Verbeiren T, De Maeyer D, Reumers J, Saeys Y, Aerts S (2020) A scalable SCENIC workflow for single-cell gene regulatory network analysis. Nat Protoc 15:2247–2276. https://doi.org/10.1038/s41596-020-0336-2

    Article  CAS  PubMed  Google Scholar 

  19. Wolf FA, Hamey FK, Plass M, Solana J, Dahlin JS, Göttgens B, Rajewsky N, Simon L, Theis FJ (2019) PAGA: graph abstraction reconciles clustering with trajectory inference through a topology preserving map of single cells. Genome Biol 20:59. https://doi.org/10.1186/s13059-019-1663-x

    Article  PubMed  PubMed Central  Google Scholar 

  20. Yachie-Kinoshita A, Onishi K, Ostblom J, Langley MA, Posfai E, Rossant J, Zandstra PW (2018) Modeling signaling-dependent pluripotency with Boolean logic to predict cell fate transitions. Mol Syst Biol 14. https://doi.org/10.15252/msb.20177952

  21. Yuh C-H, Moore JG, Davidson EH (1996) Quantitative functional interrelations within the cis-regulatory system of the S. purpuratus Endo16 gene. Development 122:4045–4056

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Funding: TH and PWZ were supported by the Canadian Institutes of Health Research (CIHR), Foundation Grant FRN 154283, and the Natural Sciences and Engineering Research Council of Canada (NSERC), Discovery Grant RGPIN-2020-06496), to PWZ. PWZ is the Canada Research Chair in Stem Cell Bioengineering (https://www.chairs-chaires.gc.ca). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors declare that no competing interests exist.

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2023 Springer Science+Business Media, LLC

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Heydari, T., Zandstra, P.W. (2023). Inferring Gene Regulatory Networks and Predicting the Effect of Gene Perturbations via IQCELL. In: Zernicka-Goetz, M., Turksen, K. (eds) Embryo Models In Vitro. Methods in Molecular Biology, vol 2767. Humana, New York, NY. https://doi.org/10.1007/7651_2022_465

Download citation

  • DOI: https://doi.org/10.1007/7651_2022_465

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3685-5

  • Online ISBN: 978-1-0716-3686-2

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics