Bacarena: Individual Based Metabolic Analysis of Cellular Communities in Their Environments

BacArena: Individual based metabolic analysis of cellular communities in their environments

Eugen Bauer¹, Johannes Zimmermann², Ines Thiele¹ and Christoph Kaleta²

1. University of Luxembourg, Luxembourg Centre for Systems Biomedicine, L-4362 Esch-sur-Alzette, Luxembourg

2. Research Group Medical Systems Biology, Institute for Experimental Medicine, ChristianAlbrechts-University Kiel, 24105 Kiel, Germany

Classical approaches in biology and systems biology have broadened our understanding of the metabolic processes within a single cell. However, recent advances focus more and more on populations of several individuals and species (1). This is in particular important for understanding the involvement of cellular communities in human health and disease, as well as biotechnological approaches optimizing the production and consumption of certain compounds. While traditional methods, such as flux balance analysis model specific states of cell metabolism (2), ecological modeling approaches, such as individual based modeling, can study spatio-temporal dynamics of whole populations. In this study, we present the new object oriented R package BacArena, which combines both techniques to study the metabolic as well as physical interactions of cellular communities. In our framework constraint based modeling was implemented using the R package sybil (3) and allows to manipulate and modify the underlying metabolic model dynamically.
We compare the results of our approach with established modeling methods in microbial communities and discuss novel functionalities. In particular, we show that the spatial structure of multi-species communities matters for their interactions with each other and is therefore relevant to study with such multi-scale modeling tools.
Through its modular object oriented structure BacArena is easy to use and extendable to model further interactions. Furthermore, additional data, such as high throughput sequencing and metabolomics, can be analyzed in R and subsequently integrated in BacArena to model condition specific cellular communities.

1. Harcombe WR, Riehl WJ, Dukovski I, Granger BR, Betts A, Lang AH, et al. Metabolic resource allocation in individual microbes determines ecosystem interactions and spatial dynamics. Cell reports. 2014;7(4):1104-15.

2. Orth JD, Thiele I, Palsson BØ. What is flux balance analysis? Nature biotechnology. 2010;28(3):245-8.

3. Gelius-Dietrich G, Desouki AA, Fritzemeier CJ, Lercher MJ. sybil–Efficient constraint-based modelling in R. BMC systems biology. 2013;7(1):125.