# Characterizing behavioural differentiation in gene regulatory networks with representation graphs

**Authors:** Juris Viksna, Karlis Cerans, Lelde Lace, Gatis Melkus

PMC · DOI: 10.1093/nargab/lqae102 · NAR Genomics and Bioinformatics · 2024-08-09

## TL;DR

This paper introduces a new way to visualize and understand gene regulatory networks using representation graphs, which help explain how cells differentiate into distinct behaviors.

## Contribution

The novel contribution is the introduction of representation graphs to compactly capture and analyze stable states and differentiation processes in gene regulatory networks.

## Key findings

- Representation graphs can capture differentiation processes into lytic and lysogenic states in phage viruses with consistent structure despite different mechanisms.
- The approach is effective for modeling myeloid cell differentiation from a common progenitor into distinct cell types.
- Representation graphs can derive and validate hypotheses about regulatory interactions necessary for biologically viable behaviors.

## Abstract

We introduce the formal notion of representation graphs, encapsulating the state space structure of gene regulatory network models in a compact and concise form that highlights the most significant features of stable states and differentiation processes leading to distinct stability regions. The concept has been developed in the context of a hybrid system-based gene network modelling framework; however, we anticipate that it can also be adapted to other approaches of modelling gene networks in discrete terms. We describe a practical algorithm for representation graph computation as well as two case studies demonstrating their real-world application and utility. The first case study presents models for three phage viruses. It shows that the process of differentiation into lytic and lysogenic behavioural states for all these models is described by the same representation graph despite the distinctive underlying mechanisms for differentiation. The second case study shows the advantages of our approach for modelling the process of myeloid cell differentiation from a common progenitor into different cell types. Both case studies also demonstrate the potential of the representation graph approach for deriving and validating hypotheses about regulatory interactions that must be satisfied for biologically viable behaviours.

## Full-text entities

- **Genes:** xis [NCBI Gene 2703504], KLF1 (KLF transcription factor 1) [NCBI Gene 10661] {aka CDAN4A, CDAN4B, EKLF, EKLF/KLF1}, cII [NCBI Gene 2703494], TRU-TCA1-1 (tRNA-SeC (anticodon TCA) 1-1) [NCBI Gene 7234] {aka THMA3, TRNAU1, TRSP, tRNA(Sec)}, cIII [NCBI Gene 3827056], cI [NCBI Gene 3827059], JUN (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3725] {aka AP-1, AP1, c-Jun, cJUN, p39}, FLI1 (Fli-1 proto-oncogene, ETS transcription factor) [NCBI Gene 2313] {aka BDPLT21, EWSR2, FLI-1, SIC-1}, cro [NCBI Gene 2703467], CEBPA (CCAAT enhancer binding protein alpha) [NCBI Gene 1050] {aka C/EBP-alpha, CEBP}, GATA1 (GATA binding protein 1) [NCBI Gene 2623] {aka CNSHA9, ERYF1, GATA-1, GF-1, GF1, HAEADA}, GATA2 (GATA binding protein 2) [NCBI Gene 2624] {aka DCML, IMD21, MONOMAC, NFE1B}, GFI1 (growth factor independent 1 transcriptional repressor) [NCBI Gene 2672] {aka GFI-1, GFI1A, SCN2, ZNF163}, SIX5 (SIX homeobox 5) [NCBI Gene 147912] {aka BOR2, DMAHP}, LCT (lactase) [NCBI Gene 3938] {aka LAC, LPH, LPH1}, xis [NCBI Gene 1262493], SPI1 (Spi-1 proto-oncogene) [NCBI Gene 6688] {aka AGM10, OF, PU.1, SFPI1, SPI-1, SPI-A}, ACSBG1 (acyl-CoA synthetase bubblegum family member 1) [NCBI Gene 23205] {aka BG, BG1, BGM, GR-LACS, LPD}, INTU (inturned planar cell polarity protein) [NCBI Gene 27152] {aka CPLANE4, INT, OFD17, PDZD6, PDZK6, SRTD20}, ZFPM1 (zinc finger protein, FOG family member 1) [NCBI Gene 161882] {aka FOG, FOG1, PRDM18, ZC2HC11A, ZNF89A}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}
- **Diseases:** infection (MESH:D007239)
- **Chemicals:** A (MESH:D001151), GMP (-)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Bacteriophage sp. (species) [taxon 38018], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** HK022 — Homo sapiens (Human), Laryngeal squamous cell carcinoma, Cancer cell line (CVCL_5991)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11310862/full.md

## References

27 references — full list in the complete paper: https://tomesphere.com/paper/PMC11310862/full.md

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Source: https://tomesphere.com/paper/PMC11310862