About

Abasy Atlas provides a comprehensive atlas of annotated functional systems (hereinafter also referred as modules), global network properties, and system-level elements predicted by the natural decomposition approach[1,2,3] (NDA) for reconstructed and meta-curated regulatory networks across a large range of bacteria, including pathogenic and biotechnologically relevant organisms. Regulatory networks could be thought of as a “take decisions” organ in bacteria. They not only sense stimulus and respond accordingly but, for example, in a complex environment, they “take composite decisions” to prioritize the assimilation and catabolism of carbon sources according to the metabolic preferences of each organism. To accomplish this, RNs composed by thousands of regulatory interactions, must follow well-defined organization principles governing their dynamics.

In the last decades of the 20th century, the first levels of gene organization were unveiled as the operon and the regulon[2]. Currently, a few databases (RegulonDB, SubtiWiki, DBTBS, CoryneRegNet, and RegTransBase) extract, by manual curation of literature, the molecular knowledge about gene regulation in different organisms providing an invaluable source of information. Nevertheless, information on these databases never goes beyond the regulon level, whereas cumulative evidence has showed that regulatory networks are complex hierarchical-modular networks whose organizational and evolutionary principles are pivotal for determining the dynamics of the cell and still challenging our understanding. In this atlas, we take the first step towards a global understanding of the regulatory networks organization by building a cartography of the functional architecture for each of the best-studied organisms.

Citation policy

If you want to reference Abasy Atlas, data provided or any generated image, please cite:

Ibarra-Arellano, M.A., Campos-González, A.I., Treviño-Quintanilla, L.G., Tauch, A., Freyre-González, J.A. Abasy Atlas: a comprehensive inventory of systems, global network properties and systems-level elements across bacteria. Database 2016:baw089 (2016) doi:10.1093/database/baw089

The natural decomposition approach

The NDA defines criteria to identify systems and system-level elements in a regulatory network, and rules to reveal its functional architecture by controlled decomposition (Figure 1). This biologically motivated approach mathematically derives the architecture and system-level elements from the global structural properties of a given regulatory network. It is based on two biological premises[1]:

  1. A module is a set of genes cooperating to carry out a particular physiological function, thus conferring different phenotypic traits to the cell.
  2. Given the pleiotropic effect of global regulators, they must not belong to modules but rather coordinate them in response to general-interest environmental cues.

According to this approach, every gene in a regulatory network is predicted to belong to one out of four possible classes of system-level elements, which interrelate in a non-pyramidal, three-tier, hierarchy shaping the functional architecture as follows[1,2,3]: (1) Global regulators are responsible for coordinating both the (2) basal cell machinery, composed of exclusively globally regulated genes (EGRGs), and (3) locally autonomous modules (shaped by modular genes), whereas (4) intermodular genes integrate, at promoter level, physiologically disparate module responses eliciting a combinatorial processing of environmental cues (Figure 2).

There are a couple of advantages resulting from developing an ad-hoc method based on biological knowledge: (1) Global regulators (hubs) does not belong to any module. This is biologically important because they are not related to a particular physiologic function. (2) We identify that there are overlap among modules and it is mediated by the intermodular genes. None of this key features existing in bacterial regulatory networks could be identified with any of the methods commonly used to identify communities in complex networks.

Figure 1. The natural decomposition approach.
Figure 2. The functional architecture unveiled by the NDA is a diamond-shaped, three-tier hierarchy, exhibiting some feedback between processing and coordination layers, which is shaped by four classes of system-level elements: global regulators, locally autonomous modules, basal machinery, and intermodular genes.

Credits

Abasy Atlas is actively developed by the Regulatory Systems Biology Research Group at the Program of Evolutionary Genomics, Center for Genomic Sciences (CCG), UNAM:

Project leader: Automated data extraction, gene symbols disambiguation and meta-curation: Automated NDA predictions and functional annotation: Web and database programming:
  • Julio A. Freyre-González, PhD (CCG, UNAM)
  • Josué Jiménez (ITZ)
Interactive network panel programming: External contributors:

Funding

The development of Abasy Atlas was supported by grants IA200614 and IA200616 from PAPIIT-UNAM to Julio A. Freyre-González.

References

  1. Freyre-González, J.A., Treviño-Quintanilla, L.G., Valtierra-Gutiérrez, I., Gutierrez-Ríos, R.M., and Alonso-Pavón, J.A. Prokaryotic regulatory systems biology: Common principles governing the functional architectures of Bacillus subtilis and Escherichia coli unveiled by the natural decomposition approach. Journal of Biotechnology 161(3):278-286 (2012)
  2. Freyre-González, J.A. and Treviño-Quintanilla, L.G. Analyzing regulatory networks in bacteria. Nature Education 3(9):24 (2010)
  3. Freyre-González, J.A., Alonso-Pav√≥n, J.A., Treviño-Quintanilla, L.G., and Collado-Vides, J. Functional architecture of Escherichia coli: new insights provided by a natural decomposition approach. Genome Biology 9(10):R154 (2008)