Metacode: One code to rule them all.

The code of codes or metacode is a microcosm where biological layers, as well as their codes, interact together allowing the continuity of information flow in organisms by increasing biological entities' complexity. Through this novel organic code, biological systems scale towards niches with higher informatic freedom building structures that increase the entropy in the universe. Code biology has developed a novel informational framework where biological entities strive themselves through the information flow carried out through organic codes consisting of two molecular or functional landscapes intertwined through arbitrary linkages via an adaptor whose nature is autonomous from molecular determinism. Here we will integrate genomic and epigenomic codes according to the evidence released in ENCODE (phase 3), psychENCODE and GTEx project, outlining the principles of the metacode, to address the continuous nature of biological systems and their inter-layered information flow. This novel complex metacode maps from very constrained sets of elements (i.e., regulation sites modulating gene expression) to new ones with greater freedom of decoding (i.e., a continuous cell phenotypic space). This leads to a new domain in code biology where biological systems are informatic attractors that navigate an energy metaspace through a complexity-noise balance, stalling in emergent niches where organic codes take meaning.

Review article: shared disease mechanisms between non-alcoholic fatty liver disease and metabolic syndrome - translating knowledge from systems biology to the bedside.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide. Characterised by abnormal fat accumulation in the liver, NAFLD presents high degree of comorbidity with disorders of the metabolic syndrome, including type 2 diabetes, obesity and cardiovascular disease. These comorbidities have strong negative impact on the natural course of NAFLD and vice versa, whereby the presence of NAFLD substantially modifies the course and prognosis of metabolic syndrome-associated diseases. AIM: To use systems biology strategies to interrogate disease mechanisms that are common to NAFLD and metabolic syndrome. METHODS: We mapped shared gene/protein-disease interaction networks, we performed gene-disease enrichment analysis to assess pleiotropy, and we created a gene-drug connectivity network. RESULTS: We found that a shared network of genes/proteins is overrepresented by immune response-related pathways, post-translational modifications of nuclear receptors, and platelet-related processes, including activation and platelet signalling. Likewise, gene-based disease-enrichment analysis suggested underlying molecular effectors that are shared with major systemic disorders, including diverse autoimmune diseases, kidney, respiratory and nervous system disorders, cancer and infectious diseases. The shared list of genes/proteins was enriched in drug targets for anti-inflammatory therapy, drugs used to treat cardiovascular diseases, antimicrobial agents and phytochemicals, among many other approved pharmaceutical compounds. By leveraging on publicly available OMICs data, we were able to show that shared loci are not necessarily affected by reverse causality. CONCLUSION: We provide evidence indicating that NAFLD treatment, including severe histological traits, cannot be limited to the use of a single drug, as it rather requires a multi-target therapeutic approach.

Network Medicine: A Mandatory Next Step for Inflammatory Bowel Disease.

Despite unquestionable progress in the management of inflammatory bowel disease (IBD) and the much improved clinical results achievable today in Crohn's disease (CD) and ulcerative colitis (UC) patients, the overall therapeutic outcome remains far from optimal. The main reason of this partial success is that all current medications only block individual components of a highly complex disease process that results from the integration of multiple and incompletely identified pathogenic components. Thus, if further progress is to be achieved in IBD therapeutics and we want to move from the current success rate to nearly 100%, bold new ideas must be entertained and new approaches put into practice. Both are necessary because in IBD we are dealing with a prototypical complex disease superimposed to the background of the extreme biological diversity of humans in response to injury. An unresolved challenge mandates the adoption of new solutions specifically designed to address the unique features of that challenge. Translated to a disease condition, and IBD in particular, the unresolved challenges of CD and UC demand bold new thinking leading to the conception and implementation of totally innovative therapies. In this article, we propose that one such new thinking is the notion of network medicine for IBD, and that the development of brand new treatments should be based on the identification of the molecular structure of the IBD interactome with the purpose of targeting its controlling elements (central nodes or hubs). This specific targeting of the underlying molecular disease modules will lead to the disruption of the IBD interactome and foster the resolution of intestinal inflammatory process.

Clinical and diagnostic utility of saliva as a non-invasive diagnostic fluid: a systematic review.

This systematic review presents the latest trends in salivary research and its applications in health and disease. Among the large number of analytes present in saliva, many are affected by diverse physiological and pathological conditions. Further, the non-invasive, easy and cost-effective collection methods prompt an interest in evaluating its diagnostic or prognostic utility. Accumulating data over the past two decades indicates towards the possible utility of saliva to monitor overall health, diagnose and treat various oral or systemic disorders and drug monitoring. Advances in saliva based systems biology has also contributed towards identification of several biomarkers, development of diverse salivary diagnostic kits and other sensitive analytical techniques. However, its utilization should be carefully evaluated in relation to standardization of pre-analytical and analytical variables, such as collection and storage methods, analyte circadian variation, sample recovery, prevention of sample contamination and analytical procedures. In spite of all these challenges, there is an escalating evolution of knowledge with the use of this biological matrix.

Modeling cancer: integration of "omics" information in dynamic systems.

The last 10 years have seen the rise of many technologies that produce an unprecedented amount of genome-scale data from many organisms. Although the research community has been successful in exploring these data, many challenges still persist. One of them is the effective integration of such data sets directly into approaches based on mathematical modeling of biological systems. Applications in cancer are a good example. The bridge between information and modeling in cancer can be achieved by two major types of complementary strategies. First, there is a bottom-up approach, in which data generates information about structure and relationship between components of a given system. In addition, there is a top-down approach, where cybernetic and systems-theoretical knowledge are used to create models that describe mechanisms and dynamics of the system. These approaches can also be linked to yield multi-scale models combining detailed mechanism and wide biological scope. Here we give an overall picture of this field and discuss possible strategies to approach the major challenges ahead.