Integrating Microarray Data and GRNs.

With the completion of the Human Genome Project and the emergence of high-throughput technologies, a vast amount of molecular and biological data are being produced. Two of the most important and significant data sources come from microarray gene-expression experiments and respective databanks (e,g., Gene Expression Omnibus-GEO (http://www.ncbi.nlm.nih.gov/geo)), and from molecular pathways and Gene Regulatory Networks (GRNs) stored and curated in public (e.g., Kyoto Encyclopedia of Genes and Genomes-KEGG (http://www.genome.jp/kegg/pathway.html), Reactome (http://www.reactome.org/ReactomeGWT/entrypoint.html)) as well as in commercial repositories (e.g., Ingenuity IPA (http://www.ingenuity.com/products/ipa)). The association of these two sources aims to give new insight in disease understanding and reveal new molecular targets in the treatment of specific phenotypes.Three major research lines and respective efforts that try to utilize and combine data from both of these sources could be identified, namely: (1) de novo reconstruction of GRNs, (2) identification of Gene-signatures, and (3) identification of differentially expressed GRN functional paths (i.e., sub-GRN paths that distinguish between different phenotypes). In this chapter, we give an overview of the existing methods that support the different types of gene-expression and GRN integration with a focus on methodologies that aim to identify phenotype-discriminant GRNs or subnetworks, and we also present our methodology.

Modeling susceptibility to periodontitis.

Chronic inflammatory diseases like periodontitis have a complex pathogenesis and a multifactorial etiology, involving complex interactions between multiple genetic loci and infectious agents. We aimed to investigate the influence of genetic polymorphisms and bacteria on chronic periodontitis risk. We determined the prevalence of 12 single-nucleotide polymorphisms (SNPs) in immune response candidate genes and 7 bacterial species of potential relevance to periodontitis etiology, in chronic periodontitis patients and non-periodontitis control individuals (N = 385). Using decision tree analysis, we identified the presence of bacterial species Tannerella forsythia, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and SNPs TNF -857 and IL-1A -889 as discriminators between periodontitis and non-periodontitis. The model reached an accuracy of 80%, sensitivity of 85%, specificity of 73%, and AUC of 73%. This pilot study shows that, on the basis of 3 periodontal pathogens and SNPs, patterns may be recognized to identify patients at risk for periodontitis. Modern bioinformatics tools are valuable in modeling the multifactorial and complex nature of periodontitis.

Nanoinformatics: developing new computing applications for nanomedicine.

Nanoinformatics has recently emerged to address the need of computing applications at the nano level. In this regard, the authors have participated in various initiatives to identify its concepts, foundations and challenges. While nanomaterials open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treatment of diseases. In this paper, we analyze the different aspects of nanoinformatics and suggest five research topics to help catalyze new research and development in the area, particularly focused on nanomedicine. We also encompass the use of informatics to further the biological and clinical applications of basic research in nanoscience and nanotechnology, and the related concept of an extended "nanotype" to coalesce information related to nanoparticles. We suggest how nanoinformatics could accelerate developments in nanomedicine, similarly to what happened with the Human Genome and other -omics projects, on issues like exchanging modeling and simulation methods and tools, linking toxicity information to clinical and personal databases or developing new approaches for scientific ontologies, among many others.

International efforts in nanoinformatics research applied to nanomedicine.

BACKGROUND: Nanomedicine and nanoinformatics are novel disciplines facing substantial challenges. Since nanomedicine involves complex and massive data analysis and management, a new discipline named nanoinformatics is now emerging to provide the vision and the informatics methods and tools needed for such purposes. Methods from biomedi-cal informatics may prove applicable with some adaptation despite nanomedicine involving different biophysical and biochemical characteristics of nanomaterials and corresponding differences in information complexity. OBJECTIVES: We analyze recent initiatives and opportunities for research in nanomedicine and nanoinformatics as well as the previous experience of the authors, particularly in the context of a European project named ACTION-Grid. In this project the authors aimed to create a collaborative environment in biomedical and nanomedical research among countries in Europe, Western Balkans, Latin America, North Africa and the USA. METHODS: We review and analyze the rationale and scientific issues behind the new fields of nanomedicine and nanoinformatics. Such a review is linked to actual research projects and achievements of the authors within their groups. RESULTS: The work of the authors at the intersection between these two areas is presented. We also analyze several research initiatives that have recently emerged in the EU and USA context and highlight some ideas for future action at the international level. CONCLUSIONS: Nanoinformatics aims to build new bridges between medicine, nanotechnology and informatics, allowing the application of computational methods in the nano-related areas. Opportunities for world-wide collaboration are already emerging and will be influential in advancing the field.

A semantically aware platform for the authoring and secure enactment of bioinformatics workflows.

Recent advances in the field of bioinformatics present a number of challenges in the secure and efficient management and analysis of biological data resources. Workflow technologies aim to assist scientists and domain experts in the design of complex, long running, data and computing intensive experiments that involve many data processing and analysis tasks with the objective of generating new knowledge or formulate new hypothesis. In this paper we present a bioinformatics workflow authoring and execution environment that intends to greatly facilitate the whole lifecycle of such experiments. Emphasis is given on the security and ethical requirements of these scenarios and the corresponding technological response. In addition we present our semantic framework used for supporting specific user-requirements related to the reasoning and inference capabilities of the environment.

Functional specifications of an integrated proteomics information management and analysis platform.

Detecting proteins in human blood holds the promise of a revolution in cancer diagnosis. Also, the ability to perform laboratory operations on small scales using miniaturized (lab-on-a-chip) devices has many benefits. Designing and fabricating such systems is extremely challenging, but physicists and engineers are beginning to construct such highly integrated and compact labs on chips with exciting functionality. This paper focuses on the presentation of the requirements of the information technology layer in such an integrated platform been developed in the LOCCANDIA project. LOCCANDIA is a Specific Targeted Research project (STREP) funded under the 6th Framework program of the EC. Its ultimate objective is to develop an innovative nano-technology based (lab-on-a-chip) platform for the medical-proeomics field. The paper presents the main engineering aspects, challenges and architecture for creating an Integrated Clinico-Proteomic Environment. The environment will be used to monitor and document the analysis and discovery chain and to allow the physician to interpret the digital spectrogram data delivered by the mass spectrometer, for diagnostic purposes.

Building a European biomedical grid on cancer: the ACGT Integrated Project.

This paper presents the needs and requirements that led to the formation of the ACGT (Advancing Clinico Genomic Trials) integrated project, its vision and methodological approaches of the project. The ultimate objective of the ACGT project is the development of a European biomedical grid for cancer research, based on the principles of open access and open source, enhanced by a set of interoperable tools and services which will facilitate the seamless and secure access to and analysis of multi-level clinico-genomic data, enriched with high-performing knowledge discovery operations and services. By doing so, it is expected that the influence of genetic variation in oncogenesis will be revealed, the molecular classification of cancer and the development of individualised therapies will be promoted, and finally the in-silico tumour growth and therapy response will be realistically and reliably modelled. Its main design decisions and results at its current stage of development are presented.

Role-based access to patients clinical data: the InterCare approach in the region of Crete.

The basics of a particular Integrated Electronic Health Record (I-EHR) implementation are presented, as realised by the Patient Clinical Data Directory (PCDD) system. PCDD operates within the context of HYGEIAnet, the Integrated Healthcare Telematics Network of Crete. PCDD is based on a federation of autonomous information systems and provides to its authorized users alternative views of the health record as well as access and retrieval services to its geographically distributed segments. The data model of the PCDD is based on the Subjective Objective Assessment Plan (SOAP) model that originates from the primary healthcare domain. Access to detailed information on particular patients healthcare encounters is delivered via role-based authorization privileges and controls. The administration of the national healthcare organizations' business rules, for different user-groups, is made via a specially tailored and developed rule-editor.