WP5 : Methods, Technologies & Tools

WP5: Methods, Technologies & Tools Work in the last year +1st George Potamias Vassilis Moustakis …. Institute of Computer Science (ICS) FORTH

Web-site … for REVIEW WP5: Methods, Technologies & Tools (1st year) SoA on Systems, Methods & Tools in BMI

WP5: Methods, Technologies & Tools (2nd year) D13 … after REVIEW partners, SAB members • First report on systems interoperability for data analysis, information retrieval and decision support • Collaboration between all INFOBIOMED partners • Basic work of WP5 for the first 19 months Rational • To sensitive, aware, informthe related communities about advances in BioMedical Informatics (WP2: Dissemination). • Educate them about BMI SoA methods in order to tackle related biomedical problems and tasks (WP3: Education). • Single-stop reference to BMI tasks, methods, technologies and tools. • As a ‘consultation’ service for INFOBIOMED pilots (WP6: Pilots). • Enabling clinico-genomics research and clinico-genomic trials. • Integrated Clinico-Genomics Environment(WP4: Standards). • Special focus on biomedical knowledge discovery. George Potamias (FORTH; Editor) Lead participant: FORTH Date: 23/01/2006 Type: Deliverable Dissemination level: Public Key-points

WP5: Methods, Technologies & Tools (1st/2nd years) D13: Structure … oriented around ‘biomedical-tasks’ Description Linksto methods, technologies, SW tools, Web-sites, databases, … References

Section 1:Biomedical Informatics • ‘hot’ biomedical tasks • ‘key’ technologies to tackle them • towards an ‘operational’ definition of BMI … a scientific discipline • linkage and synergies between BI and MI Section 2:Bioinformatics • genomicinformation and data analysis tasks • BI approaches (technology, systems and tools) to tackle them Section 3:Medical Informatics • clinicalinformation and data analysis tasks • MI approaches (technology, systems and tools) to tackle them enabling BMI infrastructure WP5: Methods, Technologies & Tools (2nd year) D13: Summary

WP5: Methods, Technologies & Tools (2nd year) D13: The BMI context • Biology / BI • Human Genome Annotation  Polymorphisms • Biology & Medicine / BI & MI •  Phenotyping •  Individualized/Genomic Medicine •  Oncogenomics •  Tissue Microarrays • BI/MI •  Pharmacogenetic •  Environment / Epigenetics

WP5: Methods, Technologies & Tools (2nd year) D13: BMI … a Scientific Discipline … draws on and contribute to computer science, … closely related to the decision, cognitive, information and management sciences ….BMI researcher tightly linked to some underlying problem from the real world of health or biomedicine • BMI spans the spectrum from the theoretical to the applied, it has equally-developed ´basic science´ and ´clinical´ components • In addition, there is a strong component comprised of organizational theory and applications tailored to health-care systems and institutions.

WP5: Methods, Technologies & Tools (2nd year) D13:BMI ‘vertical’ / ‘horizontal’ dimensions

WP5: Methods, Technologies & Tools (2nd year) D13: The BMI TARGETs

WP5: Methods, Technologies & Tools (2nd year) D13:BMI & GRID technology … a ‘must’

Genome Database Mining Structural annotation Computational/Mining for Gene Discovery Comparative Genomics Gene Expression Mining Proteomics and Data Mining Metabolomics and Data Mining Standards / Environment PMML(Predictive Model Markup Language) R-package: An integrated environment for data-mining BBR tools WP5: Methods, Technologies & Tools (2nd year) D13:BMI & Knowledge Discovery

“The ability to detect, through imaging, the molecular changes associated with a tumor cell will improve our ability to detect and stage tumors, select appropriate treatments, monitor the effectiveness of a treatment, and determine prognosis.” Ellen Feigal (MD, Acting Director, Division of Cancer Treatment and Diagnosis, National Cancer Institute, USA) Direct approaches.e.g., Monoclonal antibody targeting of a particular enzyme (e.g., hexokinase) with an enzyme-specific probe (e.g. deoxyglucose), using nuclear medicine  PET Biomarker approaches. Molecular indicator of a specific biological property; to monitor down-stream effects of changes in specific molecular-genetic pathways in diseases Indirect approaches. Imaging a reporter-gene using probes (e.g. transgene HSV1-tk) – to develope gene-therapies, visualization of regulation of gene-expression and intracellular protein-protein interactions Microarray Imaging Informatics WP5: Methods, Technologies & Tools (2nd year) D13:BMI &(Medical) Molecular Imaging • Key criteria : • High affinity probes with reasonable pharmacodynamics; • The probes to overcome biologic delivery barriers (vascular, cell membrane); • Use of amplification strategies (chemical or biologic); • Availability of sensitive, fast, high-resolution imaging techniques.

WP5: Methods, Technologies & Tools (2ndyear) D13:Contents - BMI

WP5: Methods, Technologies & Tools (2nd year) D13:Contents - BI

WP5: Methods, Technologies & Tools (2nd year) D13:Contents - MI

WP5: Methods, Technologies & Tools WP5 in support of WP6 pilots material / links / references … on partners’ bilateralcollaboration … exploit SoA / D13 methods, technologies, tools 2 examples 

WP5: Methods, Technologies & Tools WP5 WP6.1

WP5 in support of WP6 pilots (2nd year) WP5  WP6.1:Pharmainformatics Biomedical Text Mining Data Analysis: Clustering MI-EMC (Erasmus)  AstraZeneca

WP5 in support of WP6 pilots (2nd year) WP5/WP4  WP6.1:Pharmainformatics Molecular Pathways: Model, Represent, Reason & Visualize WP5, WP4 (standards)

WP5 in support of WP6 pilots (2nd year) WP5  WP6.2:Genomics & Infection UEDIN /GTI  FORTH Validation and Novel miRNA targets The basic Task Overlap of predicted miRNA target networks onto the interferon network in order to understand how miRNAs may act to control the expression of interferon-related proteins in vivo. • BioInformaticsSystems, Methods and Tools for miRNA prediction • Prediction of host target sites for viral miRNA binding • Prediction of viral target sites for host miRNA binding • Prediction of viral target sites for viral miRNA binding • Prediction of host interferon-related target sites for predicted host miRNA binding

WP5 in support of WP6 pilots (2nd year) WP5  WP6.2:miRNA prediction Genome wide prediction the pipeline 2 851 352 871 bases Feature Extraction: Energy + structural features full genome Classification SVM SEARCH: windows of 104 nt along genome Cross-species conservation FILTERING: Inverted repeats/composition & palindromes HMM RNA secondary structure prediction: using novel Dynamic programming algorithm • Novel microRNAs … involved in intreferon and herpes virus pathways • Microarray verification

WP5 in support of WP6 pilots (2nd year) WP5  WP6.2:miRNA prediction …and the GO terms of all genes regulated by it A miRNA Visualization of miRNA regulation

WP5 in support of WP6 pilots (2nd year) WP5  WP6.2:miRNA prediction Preliminary results:All miRNA targets (in IFN map) with high score miRNA-ID HUGO Ensembl-ID miranda- Score -------------------------------------------------- Single targets: miRUL22A-1_3p HSPA5 ENSG00000044574 119 miRUL22A-1_3p CTSS ENSG00000163131 127 miRUL112-1_3p CBFB ENSG00000067955 113 miRUL112-1_3p DAP ENSG00000112977 132 miRUL148D-1_3p SOCS3 ENSG00000184557 113 miR-US5-1_3p CASP8 ENSG00000064012 124 miR-US5-2_3p PSMD12 ENSG00000197170 111 miRUS33-1_5p PRKCA ENSG00000154229 112 miRUL36-1_5p BCL6 ENSG00000113916 123 Double target: miRUL36-1_5p CAMK2A ENSG00000070808 115 miRUS25-2_3p CAMK2A ENSG00000070808 114 • verification of known mouse miRNAs • Virus miRNA prediction pipeline without conservation features • miRNA scan of mouse cytomegalovirus (MCMV) • 11 high-scoring candidates sent to UEdin Collaboration with: Artemis Hatzigeorgiou, Praveen Sethupathy, Molly Megraw, Karol Szafranski Center for Bioinformatics, School of Medicine, University of Pennsylvania, USA

WP5 in support of WP6 pilots (2nd year) WP5  WP6.4:Genomics & Hereditary Colon-cancer FUNEN (HNPCC) FORTH • Various communications/contacts – meeting on November 2005 Specify, define & develop HL7 based message standards to enable and support the communication between HNPCC Danish central colon-cancer disease registry (and other registries) with genetic consulting departments, DNA-laboratories and surgery-departments • The basic Tasks • FUNEN and HNPCC have agreed on contents of 4 standards: Family, Individual, Laboratory and the Surgery message. • The aim is to get these standards adapted to HL7 in order to support seamless communication and access to relative information and data  FORTH • Medical InformaticsSystems, Methods and Tools for standardised • communication and messaging between heterogeneous clinico-genomic feeder • systems • HL7 (Health Informatics) standard methodology (version 3) • HL7 (v.3) Message Specification & Implementation technology • HL7 fundamental concepts/classes  extension to cover HNPCC domain

WP5 in support of WP6 pilots (2nd year) WP5  WP6.4:Issues & Roadmap • Issues • Not every element in the currently defined XML messages is modeled (e.g., Exon analysed in Laboratory Analysis) • The R-MIMs are developed based on the current schemas, so: • They are too specific, and therefore … • they restrict the generic use of the model HL7/SIG-Genomics Roadmap • Develop a general enough model able to accommodate the semantics of the current XML schemas leaving out unimportant details based on input from our partners • Try to find the “golden ratio” between reusability and ease of understanding and use • The Family History models of Clinical Genomics SIG of HL7 could be all that we want… but some further refinement could be needed • Follow the next steps of the HL7 v3 methodology to end up with HL7 conforming XML schemas

WP5: Methods, Technologies & Tools WP5: next 6 months ( March 2006)

WP5: Methods, Technologies & Tools … next months D13 and INFOBIOMED BMI-technology • Techniques • Systems • Tools • Case-Studies  WP6 pilots D13 as Educational Material / Reference • Index Content • Web-based material Register & Describe Present ‘utilisation’ scenarios D13 appendices … a ‘living’ document D13 WP3 BMI-terminology

WP5: INFOBIOMED Technology FORTH BMI-technology Integrated intelligent microarray data analysis tool for the discovery of molecular/gene markers and the discovery of families of co-regulated genes (metagenes) based on clustering approaches

WP5: INFOBIOMED Technology FORTH BMI-technology Integrated / Combined Clinico-Genomics Knowledge Discovery: A Multistradegy Data-Mining Approach

Advancing Clinico-Genomic Trials A new Integrated project on BMI

User Applications and services layer in support of Clinical pilots … U U The ACGT Integration Layer, the ACGT Tools and Services U Simulation and Visualization Tools D U D Knowledge Discovery Tools D U D U D Ontologies and mediation tools D D D D D Basic GRID technology and security D User Data and Public Databases Layer Distributed Biomedical Data The Vision

Symbiomatics Special Support Action – Synergy between Bioinformatics and Medical Informatics (EU-IST, 2005-2007) Beyond The Horizon(BTH) ‘Bio-ICT Synergies’ Coordinated Action, EU-FP6-FET ERCIM ‘WG on BMI’ ERCIM News, Special issue on BMI January 2005 http://www.ercim.org/publication/Ercim_News/enw60/EN60.pdf Exploitation & Concertation

WP5: Methods, Technologies & Tools Schedule October 2006

WP5: Methods, Technologies & Tools

WP5 : Methods, Technologies & Tools