Multiscale characterization of ageing and cancer progression by a novel network entropy measure.

We characterize different cell states, related to cancer and ageing phenotypes, by a measure of entropy of network ensembles, integrating gene expression profiling values and protein interaction network topology. In our case studies, network entropy, that by definition estimates the number of possible network instances satisfying the given constraints, can be interpreted as a measure of the "parameter space" available to the cell. Network entropy was able to characterize specific pathological conditions: normal versus cancer cells, primary tumours that developed metastasis or relapsed, and extreme longevity samples. Moreover, this approach has been applied at different scales, from whole network to specific subnetworks (biological pathways defined on a priori biological knowledge) and single nodes (genes), allowing a deeper understanding of the cell processes involved.

[1]  Carlo C. Maley,et al.  Clonal evolution in cancer , 2012, Nature.

[2]  A. Barabasi,et al.  Interactome Networks and Human Disease , 2011, Cell.

[3]  Gary D. Bader,et al.  Pathway Commons, a web resource for biological pathway data , 2010, Nucleic Acids Res..

[4]  L. Ferrucci,et al.  Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. , 2004, The journals of gerontology. Series A, Biological sciences and medical sciences.

[5]  Damian Szklarczyk,et al.  The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored , 2010, Nucleic Acids Res..

[6]  D. Hanahan,et al.  The Hallmarks of Cancer , 2000, Cell.

[7]  M. Pagel,et al.  Evolutionary Genomics and Proteomics , 2007 .

[8]  Ulrik Brandes,et al.  Biological Networks , 2013, Handbook of Graph Drawing and Visualization.

[9]  P. Johnston,et al.  Cancer drug resistance: an evolving paradigm , 2013, Nature Reviews Cancer.

[10]  G. Bianconi Entropy of network ensembles. , 2008, Physical review. E, Statistical, nonlinear, and soft matter physics.

[11]  M. J. van de Vijver,et al.  Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. , 2006, Journal of the National Cancer Institute.

[12]  D. Shore,et al.  Growth control and ribosome biogenesis. , 2009, Current opinion in cell biology.

[13]  Simone Brabletz,et al.  The ZEB/miR‐200 feedback loop—a motor of cellular plasticity in development and cancer? , 2010, EMBO reports.

[14]  F. Barea,et al.  Aging defined by a chronologic–replicative protein network in Saccharomyces cerevisiae: An interactome analysis , 2009, Mechanisms of Ageing and Development.

[15]  Mirko Francesconi,et al.  Overcoming resistance to conventional drugs in Ewing sarcoma and identification of molecular predictors of outcome. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  P. Pin,et al.  Assessing the relevance of node features for network structure , 2008, Proceedings of the National Academy of Sciences.

[17]  Aad van der Vaart,et al.  Statistical analysis of the cancer cell's molecular entropy using high-throughput data , 2011, Bioinform..

[18]  Ginestra Bianconi,et al.  Entropy measures for networks: toward an information theory of complex topologies. , 2009, Physical review. E, Statistical, nonlinear, and soft matter physics.

[19]  Simone Severini,et al.  Increased entropy of signal transduction in the cancer metastasis phenotype , 2010, BMC Systems Biology.

[20]  C. Franceschi,et al.  Lifelong maintenance of composition, function and cellular/subcellular distribution of proteasomes in human liver , 2014, Mechanisms of Ageing and Development.

[21]  J. Bergh,et al.  Definition of clinically distinct molecular subtypes in estrogen receptor-positive breast carcinomas through genomic grade. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  G. Castellani,et al.  Complex patterns of gene expression in human T cells during in vivo aging. , 2010, Molecular bioSystems.

[23]  G. Bianconi,et al.  Differential network entropy reveals cancer system hallmarks , 2012, Scientific Reports.

[24]  A. Barabasi,et al.  Network biology: understanding the cell's functional organization , 2004, Nature Reviews Genetics.

[25]  Javier De Las Rivas,et al.  Protein–Protein Interactions Essentials: Key Concepts to Building and Analyzing Interactome Networks , 2010, PLoS Comput. Biol..

[26]  Z. Szallasi,et al.  Evaluation of Microarray Preprocessing Algorithms Based on Concordance with RT-PCR in Clinical Samples , 2009, PloS one.

[27]  Luigi Ferrucci,et al.  Mapping the road to resilience: Novel math for the study of frailty , 2008, Mechanisms of Ageing and Development.

[28]  Ginestra Bianconi,et al.  Gibbs entropy of network ensembles by cavity methods. , 2010, Physical review. E, Statistical, nonlinear, and soft matter physics.

[29]  J. Foekens,et al.  Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer , 2005, The Lancet.