Automation on the generation of genome scale metabolic models

Background: Nowadays, the reconstruction of genome scale metabolic models is a non-automatized and interactive process based on decision taking. This lengthy process usually requires a full year of one person's work in order to satisfactory collect, analyze and validate the list of all metabolic reactions present in a specific organism. In order to write this list, one manually has to go through a huge amount of genomic, metabolomic and physiological information. Currently, there is no optimal algorithm that allows one to automatically go through all this information and generate the models taking into account probabilistic criteria of unicity and completeness that a biologist would consider. Results: This work presents the automation of a methodology for the reconstruction of genome scale metabolic models for any organism. The methodology that follows is the automatized version of the steps implemented manually for the reconstruction of the genome scale metabolic model of a photosynthetic organism, {\it Synechocystis sp. PCC6803}. The steps for the reconstruction are implemented in a computational platform (COPABI) that generates the models from the probabilistic algorithms that have been developed. Conclusions: For validation of the developed algorithm robustness, the metabolic models of several organisms generated by the platform have been studied together with published models that have been manually curated. Network properties of the models like connectivity and average shortest mean path of the different models have been compared and analyzed.Comment: 24 pages, 2 figures, 2 table

MultiMetEval: comparative and multi-objective analysis of genome-scale metabolic models

Comparative metabolic modelling is emerging as a novel field, supported by the development of reliable and standardized approaches for constructing genome-scale metabolic models in high throughput. New software solutions are needed to allow efficient comparative analysis of multiple models in the context of multiple cellular objectives. Here, we present the user-friendly software framework Multi-Metabolic Evaluator (MultiMetEval), built upon SurreyFBA, which allows the user to compose collections of metabolic models that together can be subjected to flux balance analysis. Additionally, MultiMetEval implements functionalities for multi-objective analysis by calculating the Pareto front between two cellular objectives. Using a previously generated dataset of 38 actinobacterial genome-scale metabolic models, we show how these approaches can lead to exciting novel insights. Firstly, after incorporating several pathways for the biosynthesis of natural products into each of these models, comparative flux balance analysis predicted that species like Streptomyces that harbour the highest diversity of secondary metabolite biosynthetic gene clusters in their genomes do not necessarily have the metabolic network topology most suitable for compound overproduction. Secondly, multi-objective analysis of biomass production and natural product biosynthesis in these actinobacteria shows that the well-studied occurrence of discrete metabolic switches during the change of cellular objectives is inherent to their metabolic network architecture. Comparative and multi-objective modelling can lead to insights that could not be obtained by normal flux balance analyses. MultiMetEval provides a powerful platform that makes these analyses straightforward for biologists. Sources and binaries of MultiMetEval are freely available from https://github.com/PiotrZakrzewski/MetEv​al/downloads

The future of laboratory medicine - A 2014 perspective.

Predicting the future is a difficult task. Not surprisingly, there are many examples and assumptions that have proved to be wrong. This review surveys the many predictions, beginning in 1887, about the future of laboratory medicine and its sub-specialties such as clinical chemistry and molecular pathology. It provides a commentary on the accuracy of the predictions and offers opinions on emerging technologies, economic factors and social developments that may play a role in shaping the future of laboratory medicine

Synthetic Biology: A Bridge between Artificial and Natural Cells.

Artificial cells are simple cell-like entities that possess certain properties of natural cells. In general, artificial cells are constructed using three parts: (1) biological membranes that serve as protective barriers, while allowing communication between the cells and the environment; (2) transcription and translation machinery that synthesize proteins based on genetic sequences; and (3) genetic modules that control the dynamics of the whole cell. Artificial cells are minimal and well-defined systems that can be more easily engineered and controlled when compared to natural cells. Artificial cells can be used as biomimetic systems to study and understand natural dynamics of cells with minimal interference from cellular complexity. However, there remain significant gaps between artificial and natural cells. How much information can we encode into artificial cells? What is the minimal number of factors that are necessary to achieve robust functioning of artificial cells? Can artificial cells communicate with their environments efficiently? Can artificial cells replicate, divide or even evolve? Here, we review synthetic biological methods that could shrink the gaps between artificial and natural cells. The closure of these gaps will lead to advancement in synthetic biology, cellular biology and biomedical applications

BacillOndex: An Integrated Data Resource for Systems and Synthetic Biology

BacillOndex is an extension of the Ondex data integration system, providing a semantically annotated, integrated knowledge base for the model Gram-positive bacterium Bacillus subtilis. This application allows a user to mine a variety of B. subtilis data sources, and analyse the resulting integrated dataset, which contains data about genes, gene products and their interactions. The data can be analysed either manually, by browsing using Ondex, or computationally via a Web services interface. We describe the process of creating a BacillOndex instance, and describe the use of the system for the analysis of single nucleotide polymorphisms in B. subtilis Marburg. The Marburg strain is the progenitor of the widely-used laboratory strain B. subtilis 168. We identified 27 SNPs with predictable phenotypic effects, including genetic traits for known phenotypes. We conclude that BacillOndex is a valuable tool for the systems-level investigation of, and hypothesis generation about, this important biotechnology workhorse. Such understanding contributes to our ability to construct synthetic genetic circuits in this organism

metaSHARK: software for automated metabolic network prediction from DNA sequence and its application to the genomes of Plasmodium falciparum and Eimeria tenella

The metabolic SearcH And Reconstruction Kit (metaSHARK) is a new fully automated software package for the detection of enzyme-encoding genes within unannotated genome data and their visualization in the context of the surrounding metabolic network. The gene detection package (SHARKhunt) runs on a Linux systemand requires only a set of raw DNA sequences (genomic, expressed sequence tag and/ or genome survey sequence) as input. Its output may be uploaded to our web-based visualization tool (SHARKview) for exploring and comparing data from different organisms. We first demonstrate the utility of the software by comparing its results for the raw Plasmodium falciparum genome with the manual annotations available at the PlasmoDB and PlasmoCyc websites. We then apply SHARKhunt to the unannotated genome sequences of the coccidian parasite Eimeria tenella and observe that, at an E-value cut-off of 10(-20), our software makes 142 additional assertions of enzymatic function compared with a recent annotation package working with translated open reading frame sequences. The ability of the software to cope with low levels of sequence coverage is investigated by analyzing assemblies of the E.tenella genome at estimated coverages from 0.5x to 7.5x. Lastly, as an example of how metaSHARK can be used to evaluate the genomic evidence for specific metabolic pathways, we present a study of coenzyme A biosynthesis in P.falciparum and E.tenella

WormBase: a comprehensive resource for nematode research

WormBase (http://www.wormbase.org) is a central data repository for nematode biology. Initially created as a service to the Caenorhabditis elegans research field, WormBase has evolved into a powerful research tool in its own right. In the past 2 years, we expanded WormBase to include the complete genomic sequence, gene predictions and orthology assignments from a range of related nematodes. This comparative data enrich the C. elegans data with improved gene predictions and a better understanding of gene function. In turn, they bring the wealth of experimental knowledge of C. elegans to other systems of medical and agricultural importance. Here, we describe new species and data types now available at WormBase. In addition, we detail enhancements to our curatorial pipeline and website infrastructure to accommodate new genomes and an extensive user base