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1.  Bioinformatic approaches for functional annotation and pathway inference in metagenomics data 
Briefings in Bioinformatics  2012;13(6):696-710.
Metagenomic approaches are increasingly recognized as a baseline for understanding the ecology and evolution of microbial ecosystems. The development of methods for pathway inference from metagenomics data is of paramount importance to link a phenotype to a cascade of events stemming from a series of connected sets of genes or proteins. Biochemical and regulatory pathways have until recently been thought and modelled within one cell type, one organism, one species. This vision is being dramatically changed by the advent of whole microbiome sequencing studies, revealing the role of symbiotic microbial populations in fundamental biochemical functions. The new landscape we face requires a clear picture of the potentialities of existing tools and development of new tools to characterize, reconstruct and model biochemical and regulatory pathways as the result of integration of function in complex symbiotic interactions of ontologically and evolutionary distinct cell types.
doi:10.1093/bib/bbs070
PMCID: PMC3505041  PMID: 23175748
metagenomics; next-generation sequencing; microbiome; pathway analysis; gene annotation
2.  DC-ATLAS: a systems biology resource to dissect receptor specific signal transduction in dendritic cells 
Immunome Research  2010;6:10.
Background
The advent of Systems Biology has been accompanied by the blooming of pathway databases. Currently pathways are defined generically with respect to the organ or cell type where a reaction takes place. The cell type specificity of the reactions is the foundation of immunological research, and capturing this specificity is of paramount importance when using pathway-based analyses to decipher complex immunological datasets. Here, we present DC-ATLAS, a novel and versatile resource for the interpretation of high-throughput data generated perturbing the signaling network of dendritic cells (DCs).
Results
Pathways are annotated using a novel data model, the Biological Connection Markup Language (BCML), a SBGN-compliant data format developed to store the large amount of information collected. The application of DC-ATLAS to pathway-based analysis of the transcriptional program of DCs stimulated with agonists of the toll-like receptor family allows an integrated description of the flow of information from the cellular sensors to the functional outcome, capturing the temporal series of activation events by grouping sets of reactions that occur at different time points in well-defined functional modules.
Conclusions
The initiative significantly improves our understanding of DC biology and regulatory networks. Developing a systems biology approach for immune system holds the promise of translating knowledge on the immune system into more successful immunotherapy strategies.
doi:10.1186/1745-7580-6-10
PMCID: PMC3000836  PMID: 21092113
3.  Large-scale genetic variation of the symbiosis-required megaplasmid pSymA revealed by comparative genomic analysis of Sinorhizobium meliloti natural strains 
BMC Genomics  2005;6:158.
Background
Sinorhizobium meliloti is a soil bacterium that forms nitrogen-fixing nodules on the roots of leguminous plants such as alfalfa (Medicago sativa). This species occupies different ecological niches, being present as a free-living soil bacterium and as a symbiont of plant root nodules. The genome of the type strain Rm 1021 contains one chromosome and two megaplasmids for a total genome size of 6 Mb. We applied comparative genomic hybridisation (CGH) on an oligonucleotide microarrays to estimate genetic variation at the genomic level in four natural strains, two isolated from Italian agricultural soil and two from desert soil in the Aral Sea region.
Results
From 4.6 to 5.7 percent of the genes showed a pattern of hybridisation concordant with deletion, nucleotide divergence or ORF duplication when compared to the type strain Rm 1021. A large number of these polymorphisms were confirmed by sequencing and Southern blot. A statistically significant fraction of these variable genes was found on the pSymA megaplasmid and grouped in clusters. These variable genes were found to be mainly transposases or genes with unknown function.
Conclusion
The obtained results allow to conclude that the symbiosis-required megaplasmid pSymA can be considered the major hot-spot for intra-specific differentiation in S. meliloti.
doi:10.1186/1471-2164-6-158
PMCID: PMC1298293  PMID: 16283928

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