Wellcome Trust ISSF Biomedical Informatics Hub

www.exeter.ac.uk/biomedicalhubBiomedical Informatics Hub

Wellcome Trust ISSF Biomedical Informatics HubDr Konrad PaszkiewiczContentsWellcome Trust ISSFBackgroundSeed Corn FundAimsBiomedical Informatics HubPurposeExpertiseResourcesTrainingSeminarsProject booking/PrioritisationSustainability

Institutional Strategic Support FundA 1.5 million Wellcome Trust award.. .....match funded by the University

to enhance institutional strategies for the biomedical sciences to support scientific progress, translation and interdisciplinary collaboration to encourage greater efficiency, effectiveness and accountability in the stewardship of Wellcome Trust funding

University of Exeter ISSF projectCreate a virtual Biomedical Informatics Hubto maximise output from emerging technologies and large datasetsEstablish an ISSF Seed Corn Fund to support highly-talented researchers to generate preliminary data in support of independent fellowship and grant applications8 projects supported in 2012University match-funding = new academic posts that will utilise the Hub to enable major advances in interdisciplinary biomedical research

Seed Corn FundRound 3: Who?outstanding postdoctoral researchers - to generate preliminary data to support independent Fellowship applications early career academics - to generate preliminary data in support of research grant applicationsmid-career and senior academics seeking pump priming support for new activity that will lead to a Wellcome Trust application (first time applicants to the Trust particularly encouraged) Round 3: What?Must be in the Wellcome Trusts remit5 to 7 projects (up to 12 months)Up to 20k (30k for senior researchers)Closing date = 1st Feb 2013Assessment criteriatrack recordproposed projectoutputs Contact Allison McCaig (a.mccaig@exeter.ac.uk)

Biomedical Informatics HubPurpose1. Supply informatics expertise in bioinformatics, mass-spectrometry, imaging and statistics2. Train researchers through existing and newly developed programs to make best use of their data3. Supply PhD students, postdocs and junior researchers with the tools and expertise to produce 4* research 4. Provide leadership, governance and coordination to leverage and extend Exeter's IT research infrastructure5. Support researchers with access to centralised computational infrastructure and equipment6. Act as a central point of contact for initial research ideas

ExpertiseBioinformaticsMedical - Marcus Tuke, Anna Murray & Mike Weedon (Prof. Tim Frayling)Bioscience - Dr Christine Sambles (Sequencing Service)Metabolomics/ProteomicsDr Venura Perera (Dr Hannah Florance)Image analysisDr Jeremy Metz (starting November) (Prof. Rob Beardmore)Tomography and EMTBC (Prof. Gero Steinberg)StatisticsTBC (Prof. Tim Frayling)Computational modelling/sensor-based networksDr Mahmood Javaid (Prof. Ed Watkins)ResourcesSequencing Service (Konrad Paszkiewicz, Karen Moore)Illumina HiSeq 2000 Mass-spectrometry Service (Hannah Florance)Agilent QQQAgilent QTOFMetabolomics/ProteomicsImaging (Martin Schuster, Gero Steinberg)Confocal, EM Tomography, SEM, TEMComputational ResourcesZeus cluster

ResourcesZeus Systems Biology cluster

19 nodes with 144 coresNodes have between 24Gb and 192Gb RAM150TB of storageDesigned for serial jobs, not MPI/OpenMP jobsUpcoming 150k upgrade

Contact Konrad for access

Hub Training CoursesTraining courses currently offered: Amazon EC2 cloud computingUnix & PerlShort read genomicsPhylogeneticsUse of R statistical packageRNA-seqNew courses in 2013

6. SeminarsMonthly seminars/workshop meetingsScope: bioinformatics, statistics, image analysis, programming

Submitting requestsYou can approach Hub members informally for initial discussions about projectsIf youre unsure email me

Submitting requestsBUT before they undertake any work for you:You must apply via bioinformatics-hub.ex.ac.ukAwait approval by the head of discipline (no more than a few days)You need to specify up-front outcomes in terms of grant applications and/or publications and when you expect to achieve theseAllison McCaig will review outputs. Users who use Hub time and do not publish or apply for grants outcomes will be penalised in future hub applications.

Some screenshots.....Project proposal submission

bio-informaticsHub.ex.ac.ukProject proposal submission

bio-informaticsHub.ex.ac.ukProject proposal tracking

bio-informaticsHub.ex.ac.ukPrioritisationWellcome Trust remit projects have priority to achieve extraordinary improvements in human and animal health....... we support the brightest minds in biomedical research and the medical humanities.See Research Challenges at www.wellcome.ac.uk

Seed Corn Fund projectsExisting Wellcome Trust funded projectsWellcome Trust remit researchOther research

SustainabilityFunding via the Wellcome Trust ISSF for up to three years (annual approval)To continue the Hub, we need to ensure members are costed into grant applications nowAny projects which use Hub expertise and subsequently apply for a grant need to cost relevant members Hub team presentationsVen PereraWho Am IDr Venura PereraLocated Room: M01 Mezzanine FloorBiosciencesCollege of Life and Environmental SciencesGeoffrey PopeBackground:PhD in Systems biology/BioinformaticsUsing mathematical methods for analysis of untargeted mass profiling data sets.Applied mathematicsUse of numerical methods for forecasting and predictive modeling of non-linear systemsData drive techniques for parameter optimizationOrdinary and partial differential equations for system modeling

My skillsApplied MathematicsUse of Numerical models for data modelingDevelopment of dynamic models using numerical methodsStatistical Modeling using non-parametric methodsLarge Data Sets AnalysisFocus on Untargeted Metabolite dataNew methods to solve any question Metabolite Pipeline ExSpecDevelopment of metabolite centers untargeted pipelineProgrammingJava Data ModelingR Mainly for data visualizationMatlab Data Modeling and VisualizationHTML, PHP, MySQL and basic Java Script

Further the use of MS techniquesNumerical methods for data modellingUsing probabilistic methods for data driven coupled systemsDevelopment of techniques for the MS fingerprintingUsing MS methods for polygenetic tree reconstructionMy research interests

Targeted / Quantitative Analysis

Multiple Reaction MonitoringStatistical analysis, Modelling and ClusteringSampleComparisonQuantification

Exploratory Non-targeted AnalysisExtract DataMolecular Feature Extraction (MFE) and data pre-processingMy WorkSmall Molecule analysis: Untargeted profiling and Targeted quantificationData Reduction extracted data loaded into the pipeline which Ven will explain29Targeted / Quantitative Analysis

Multiple Reaction MonitoringStatistical analysis, Modelling and ClusteringSampleComparisonQuantification

Exploratory Non-targeted AnalysisExtract DataMolecular Feature Extraction (MFE) and data pre-processing

Example ProjectTwo groups of patient types : HealthyCancerThree patientsProject Aim: Using a variety of techniques both targeted analysis as well as untargeted profiling to determine key components which are effected by the cancer

Example Project

Example ProjectPatient 24 had a large amount of inflammation causing the control and cancer tissue to share a great deal of features similarities.33http://biosciences.exeter.ac.uk/facilities/spectrometry/http://bio-massspeclocal.ex.ac.uk/

Nick Smirnoff (Director of Mass Spectrometry) N.Smirnoff@exeter.ac.ukHannah Florance (MS Facility Manager) H.V.Florance@exeter.ac.ukVenura Perera (Bioinformatics and Mathematical Support) V.perera@exeter.ac.uk

Numerical Dynamic ModelingReaction scheme:

AK: known substrate of B (can be removed if un-mappedAU: Unknown substrate of BB : Substrate to modelE : Enzyme(s) controlling the reactionC : Known product of BCU: Unknown product of BBU : Unknown substrate of CAkAUBCUCEBUExample of Substrate-Product combo

Substrate-Product combo: Switch profiles show delayed affect indicating possible reaction schemeProfiles visually illustrate similarityAkAUBCUCEBUAnna Murray & Mike Weedon

Mike Weedon, PhDLecturer in Bioinformatics and Statistics, Exeter Medical School, St Lukes CampusM.N.Weedon@exeter.ac.ukGraduate in Biochemistry and Molecular BiologyPhD in molecular genetics of type 2 diabetes, Peninsula Medical SchoolPostdoc on genetics of complex traits, Peninsula Medical SchoolCurrent research interests genome-wide investigations of monogenic and polygenic traits Anna Murray, PhDSenior Lecturer in Human Genetics, Exeter Medical School, St Lukes CampusA.Murray@exeter.ac.ukGraduate in BiologyPhD in molecular biology of T cell receptor rearrangement in coeliac disease in SouthamptonPostdoc on population genetics of Fragile X syndrome in Salisbury/SouthamptonCurrent research interests Genetics of female reproductive lifespan

Whole exome/genome sequencingENCODE and other projects to annotate non-coding genome

Genome-wide SNP and expression array studiesBiological pathway analysis

Statistical analysis of large datasetsMarcus Tuke

BackgroundComputer Science Graduate University of Exeter Medical SchoolSupercomputer systems administrator8 months working on projects at the Wellcome Trust Centre for Human GeneticsMSc Bioinformatics

42Expertise I can offer

Human Next Generation Sequence data processing and analysisHuman RNA-Seq processing and analysisComputational expertise4343Expertise I can offer

Human RNA-Seq processing and analysisHuman Next Generation Sequence data processing and analysisComputational expertise4444

Computational expertise

Help with projects that could benefit from expertise in:

Programming/scripting

Database/web development

Linux command line and cluster computing

4545Expertise I can offer

Human RNA-Seq processing and analysisComputational expertiseHuman Next Generation Sequence data processing and analysis4646Human Next Generation Sequence data processing and analysis

Align Next Generation Sequencing reads to reference genome

Pipelines to process and call variation in aligned genome including:

Pipelines to filter false positives and QC analysis

Reference GenomegccgggcDeletionSNP g>c heterozygoteRealign reads mis-aligned in genome due to indels 4747Expertise I can offer

Computational expertiseHuman Next Generation Sequence data processing and analysisHuman RNA-Seq processing and analysis4848Human RNA-Seq processing and analysis

Align RNA-Seq reads to Human Genome Transcriptome assemblyDifferential expression analysis

4949Research Interests

Understanding the genetic basis of human diseases and traits

Genome Wide Association Studies (GWAS) have identified numerous genomic regions associated with several major diseases

However, these studies have focussed mostly on common single nucleotide genetic variants

How much more disease-associated genetic variation can we discover from 'higher resolution' technologies such as next generation sequencing (NGS)?

- Rarer- Structural- Non-autosomal- Sub-groups

5050Whole-genome sequencing in the Inchianti StudyOngoing projects

A longitudinal study of aging from the Chianti region of Tuscany, Italy1453 individuals have been followed up over 4 waves since 1998Extensive phenotypic and biomedical information collectedHundreds of circulating biomarkers (e.g. Interleukins, sex hormones, vitamins) measuredRNA expression profiling in lymphocytes (Illumina 46K array)Methylation profiling (450K array)Already had the Illumina 550K SNP Chip genotypedWe are performing low-pass (median 7X) whole genome sequencing on 680 of these individuals

http://www.inchiantistudy.netRNA-Seq whole-transcriptome assembly and analysisAssemble transcriptomes for 3 primary human microvascular endothelial cells 2 treated with cathepsin L and D respectively, and 1 controlAnalyse whether there are any differences in expression of RNA between two treatments and control

5151Christine SamblesChristine's preziJeremy MetzJeremy Metz, PhDPhD: Quantum computing - theory & simulations Imperial College LondonPostdoc:Biological image analysis & cellular modelling Einstein College of Medicine, NYResearch Interests Image processing and computer vision applied to biological systemsObject segmentation Tracking in range of dynamical scenariosQuantitative analysis

Modelling biological systems - analytical and numerical approachesMonte-carlo simulationsIntegration of data and insight from multiple scales of inquiry, e.g. AFM, single cell analysis, high throughput screeningSkills and ExpertisePython, C++, Java, MatlabImage processingMatlab - image processing toolkitPython - Scipy and OpenCV bindingsJava - ImageJ pluginsSimulationC/C++ for fast low-level routinesPython as "glue" code and visualizationLinux, shell scripting, Oracle Grid Engine Past Projects - Image processingObject tracking: Developed novel cross-correlation and Bayesian state estimation based object tracker

Object segmentation: (In progress) Object detection and segmentation based on Scale-space representation formalismSimulationBiological system: Kinesin diffusion-reaction during mitosis, spindle photo -bleached at t=0. Model using minimalist feature cell:

Check for presence of competition for binding sites between diffusing species

Quantum system: Noisy (open) atom-cavity system, laser illuminationHow can we work together?

With my expertise in the fields of biological data/image analysis, and mathematical & computational modeling, how can we combine our skills to produce an outstanding research project? ExperimentsExtract dataModel, Simulation TheoryMahmood JavaidArea of expertise:Computational ModellingSensor-based Networks and Embedded SystemsHigh Performance ComputingSoftware Development

Mahmood Javaid PhD Computer scienceExperimental Officer- Research ComputingWellcome Trust Biomedical Informatics HubComputational ModellingAgent-based modelling using Agent-based simulation frameworks such as FLAME and SWARMBenefits:Close association between the model entities and the real-world agentsHeterogeneous agents within an environmentInteraction between the agents through message passingPotential to uncover emergent behavioursPossibility of multi-scale modelling

Some examplesProspecting asteroid belt

Hypothesis testing

Economics and Systems biological applications of ABMEurace project (Dept. of Computer Science, University of Sheffield.)

System Understanding of Microbial Oxygen Responses (SUMO) Sensor-based networks, embedded systemsInvolving proximity sensors such as Ultrasonic, Infrared, and Laser-based.Inertial management units such Accelerometer, Gyroscope, and Magnetometer.Interfacing between sensors and computation units using interconnects such as Serial ports, Bluetooth, and I2C.PIC and AVR microcontroller based systems Sensory augmentation deviceIn order to move around in the world safely and quickly most of us are highly reliant on our visual sense. When vision is compromised, the problem of safely finding our way becomes much more difficult.Possibility of augmenting our existing senses with a form of remote touch generated by artificial distance sensors and tactile stimulus.

Movement is critical to how we use our tactile sense.We explore objects through touch by controlling the way that we move our sensory surfaces over themstroking with the fingertips to investigate texture, for instance, or palpating to investigate shape.

Active TouchInspired from biological and biomimetics

Physical Components

First Prototype

High Performance ComputingAgent-based models running on Linux HPC clustersAdministration of Linux HPC clusterPublishing legacy applications running on Linux clusters using web-servicesSoftware DevelopmentDesktop applications for Linux and Windows platforms including MatlabWeb-based applications and publishing legacy systems using web-servicesMobile Operating System applications

Online Depression and Mood Disorder Screener

www.exeter.ac.uk/biomedicalhub

Thanks for listening.....