Website of project LifeForm

Céline Chevalier (1st year Master bioinformatics) completed in September a 3 months research internship on the construction of a Boolean network for the regulation of Bacilius Subtilis.

The objective was to build both the influence graph and the Boolean rules for the dynamics of the regulatory network of B. Subtilis, which also take into account the links with the metabolism.

The data come from a recent article gathering the knowledge of the state of the art (http://journal.frontiersin.org/article/10.3389/fmicb.2016.00275/full). The interactions are referenced in an excel file.

The student implemented in python a tool which interprets the data in the excel file to extract the influences (activations/inhibitions/unknown) between genes, and deduce some Boolean rules for the activations of the genes of the network.

Various analyses have been conducted on the resulting influence graph and Boolean network. In particular, it turns out that the network, as described in the database, contains very few feedback loop.

The model obtained at the end includes metabolites as input. Therefore,  it will allow to compute putative steady states with respect to different metabolic fluxes operating in different stages of the B. Subtilis cell cycle.

• Papers from the Newcastle group
  • Goksel Misirli, Jennifer Hallinan, and Anil Wipat. 2014. Composable Modular Models for Synthetic Biology. J. Emerg. Technol. Comput. Syst. 11, 3, Article 22 (December 2014), 19 pages. DOI
  • Curtis Madsen^†‡, James Alastair McLaughlin^†, Göksel Mısırlı^†, Matthew Pocock^†§, Keith Flanagan^†, Jennifer Hallinan^†, and Anil Wipat^*† The SBOL Stack: A Platform for Storing, Publishing, and Sharing Synthetic Biology Designs.
    ACS Synth. Biol., 2016, 5 (6), pp 487–497.DOI
  • Bartley, Bryan ; Beal, Jacob ; Clancy, Kevin ; Misirli, Goksel ; Roehner, Nicholas ; Oberortner, Ernst ; Pocock, Matthew ; Bissell, Michael ; Madsen, Curtis ; Nguyen, Tramy ; Zhang, Zhen ; Gennari, John H. ; Myers, Chris J. ; Wipat, Anil ; Sauro, Herbert . Synthetic Biology Open Language (SBOL) Version 2.0.0.
    Journal of Integrative Bioinformatics – JIB (ISSN 1613-4516).DOI
  • Göksel Mısırlı^†, Jennifer Hallinan^†∥, Matthew Pocock^†‡, Phillip Lord^†, James Alastair McLaughlin^†, Herbert Sauro^§, and Anil Wipat^*†. Data Integration and Mining for Synthetic Biology Design. ACS Synth. Biol., 2016, 5 (10), pp. 1086–1097. DOI
  • Myers CJ, Beal J, Gorochowski TE, Kuwahara H, Madsen C, McLaughlin JA, Misirli G, Nguyen T, Oberortner E, Samineni M, Wipat A, Zhang M, Zundel Z. A standard-enabled workflow for synthetic biology. Biochemical Society Transactions 2017, 45(3), 793-803.
• French side
  • H. Mandon, S. Haar and L. Paulevé.  Relationship between the Reprogramming Determinants of Boolean Networks and their Interaction Graph.  In HSB’16, LNBI. Springer, 2016. To appear. ( PDF | BibTeX + Abstract )
  • J. Kolcák, D. Šafránek, S. Haar and L. Paulevé.  Unfolding of Parametric Logical Regulatory Networks.  In SASB’16, ENTCS. Elsevier Science Publishers, 2016. To appear. ( HAL | PDF | BibTeX + Abstract )
  • Loïc Paulevé. Goal-Oriented Reduction of Automata Networks. In CMSB 2016 – 14th conference on Computational Methods for Systems Biology, volume 9859 of Lecture Notes in Bioinformatics. Springer, 2016. [ DOI:10.1007/978-3-319-45177-0_16 | PDF | URL | Bibtex ]
  • H. Mandon, S. Haar and L. Paulevé.  Temporal Reprogramming of Boolean Networks.  In CMSB’17, LNBI 10545, pages 179-195. Springer-Verlag, 2017. ( PDF | BibTeX + Abstract )
  • Th. Chatain and L. Paulevé.  Goal-Driven Unfolding of Petri Nets.  In CONCUR’17, Leibniz International Proceedings in Informatics 85, pages 18:1-18:16. Leibniz-Zentrum für Informatik, 2017. ( Web page | PDF | BibTeX + Abstract )
• Miscellaneous
  • Internship reports:
    • J. Kolcák: Efficient Analysis of Boolean Networks under Parameter Uncertainty
      
    • Clara Scherbaum: Computing Cut Sets for Petri Nets
    • Hugues Mandon: Algorithms for cellular reprogramming

Several LifeForm-related  internships took place this spring and summer; let us start with the French side:

• Clara Scherbaum worked at LSV on Computing Cut Sets for Petri Nets; she developped unfolding-based techniques for determining sets of conditions to block from being satisfied so that some given place in the Net remains unmarked; such cut sets allow to ensure health properties in biological networks.
• Juraj Kolčák studied Efficient Analysis of Boolean Networks under Parameter Uncertainty  in his master’s thesis accepted at Masaryk University, Brno, Czech Republic; the research was carried out at LSV under the joint supervision of Stefan Haar and Loïc Paulevé, together with master’s advisor David Safranek at Brno.
• Hugues Mandon successfully completed his master’s thesis on Algorithms for cellular reprogramming  with Loïc Paulevé and Stefan Haar at LRI; he is now continuing as a PhD student at LSV under Stefan Haar and Loïc Paulevé.
• Céline CHEVALIER worked with Loïc Paulevé at LRI on a logical model for transcription regulation in Bacillus subtilis ; the results of her internship are presented here .

In Newcastle,

• Delia Casas Pastor did her MSc internship at Newcastle University under the supervision of  Anil Wipat, Goksel Misirli and Wendy Smith and in cooperation with Victor Khomenko, on Deriving stress-specific biomarkers for Bacillus subtilis from the integration of RNA-seq and tiling data.