Biomedical Informatics Hub

1. Biomedical Informatics Hub www.exeter.ac.uk/biomedicalhub

2. Wellcome Trust ISSF Biomedical Informatics Hub Dr Konrad Paszkiewicz

3. Contents • Wellcome Trust ISSF • Background • Seed Corn Fund • Aims • Biomedical Informatics Hub • Purpose • Expertise • Resources • Training • Seminars • Project booking/Prioritisation • Sustainability

4. Institutional Strategic Support Fund A £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

5. University of Exeter ISSF project • Create a virtual Biomedical Informatics Hub • to maximise output from emerging technologies and large datasets • Establish an ISSF Seed Corn Fund • to support highly-talented researchers to generate preliminary data in support of independent fellowship and grant applications • 8 projects supported in 2012 • University match-funding = new academic posts • that will utilise the Hub to enable major advances in interdisciplinary biomedical research

6. Seed Corn Fund

7. Round 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 applications • mid-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)

8. Round 3: What? • Must be in the Wellcome Trust’s remit • 5 to 7 projects (up to 12 months) • Up to £20k (£30k for senior researchers) • Closing date = 1st Feb 2013 • Assessment criteria • track record • proposed project • outputs • Contact Allison McCaig (a.mccaig@exeter.ac.uk)

9. Biomedical Informatics Hub

10. Purpose 1. Supply informatics expertise in bioinformatics, mass-spectrometry, imaging and statistics 2. Train researchers through existing and newly developed programs to make best use of their data 3. 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 infrastructure 5. Support researchers with access to centralised computational infrastructure and equipment 6. Act as a central point of contact for initial research ideas

11. Expertise • Bioinformatics • Medical - Marcus Tuke, Anna Murray & Mike Weedon (Prof. Tim Frayling) • Bioscience - Dr Christine Sambles (Sequencing Service) • Metabolomics/Proteomics • Dr Venura Perera (Dr Hannah Florance) • Image analysis • Dr Jeremy Metz (starting November) (Prof. Rob Beardmore) • Tomography and EM • TBC (Prof. Gero Steinberg) • Statistics • TBC (Prof. Tim Frayling) • Computational modelling/sensor-based networks • Dr Mahmood Javaid (Prof. Ed Watkins)

12. Resources • Sequencing Service (Konrad Paszkiewicz, Karen Moore) • Illumina HiSeq 2000 • Mass-spectrometry Service (Hannah Florance) • Agilent QQQ • Agilent QTOF • Metabolomics/Proteomics • Imaging (Martin Schuster, Gero Steinberg) • Confocal, EM Tomography, SEM, TEM • Computational Resources • Zeus cluster

13. Resources • Zeus Systems Biology cluster • 19 nodes with 144 cores • Nodes have between 24Gb and 192Gb RAM • 150TB of storage • Designed for serial jobs, not MPI/OpenMP jobs • Upcoming £150k upgrade • Contact Konrad for access

14. Hub Training Courses Training courses currently offered: • Amazon EC2 cloud computing • Unix & Perl • Short read genomics • Phylogenetics • Use of R statistical package • RNA-seq New courses in 2013

15. 6. Seminars Monthly seminars/workshop meetings Scope: bioinformatics, statistics, image analysis, programming

16. Submitting requests You can approach Hub members informally for initial discussions about projects If you’re unsure – email me

17. Submitting requests • BUT before they undertake any work for you: • You must apply via bioinformatics-hub.ex.ac.uk • Await 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 these • Allison 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.

18. Some screenshots.....

19. Project proposal submission bio-informaticsHub.ex.ac.uk

20. Project proposal submission bio-informaticsHub.ex.ac.uk

21. Project proposal tracking bio-informaticsHub.ex.ac.uk

22. Prioritisation • Wellcome 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 projects • Existing Wellcome Trust funded projects • Wellcome Trust remit research • Other research

23. Sustainability • Funding 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 now • Any projects which use Hub expertise and subsequently apply for a grant need to cost relevant members

24. Hub team presentations

25. Ven Perera

26. Who Am I • Dr Venura Perera • Located Room: M01 Mezzanine Floor Biosciences College of Life and Environmental Sciences Geoffrey Pope • Background: • PhD in Systems biology/Bioinformatics • Using mathematical methods for analysis of untargeted mass profiling data sets. • Applied mathematics • Use of numerical methods for forecasting and predictive modeling of non-linear systems • Data drive techniques for parameter optimization • Ordinary and partial differential equations for system modeling

27. My skills • Applied Mathematics • Use of Numerical models for data modeling • Development of dynamic models using numerical methods • Statistical Modeling using non-parametric methods • Large Data Sets Analysis • Focus on Untargeted Metabolite data • New methods to solve any question … • Metabolite Pipeline ExSpec • Development of metabolite centers untargeted pipeline • Programming • Java  Data Modeling • R  Mainly for data visualization • Matlab  Data Modeling and Visualization • HTML, PHP, MySQL and basic Java Script

28. My research interests • Further the use of MS techniques • Numerical methods for data modelling • Using probabilistic methods for data driven coupled systems • Development of techniques for the MS fingerprinting • Using MS methods for polygenetic tree reconstruction

29. Sample Comparison Quantification Targeted / Quantitative Analysis Extract Data My Work Small Molecule analysis: Untargeted profiling and Targeted quantification Exploratory Non-targeted Analysis Multiple Reaction Monitoring Molecular Feature Extraction (MFE) and data pre-processing Statistical analysis, Modelling and Clustering

30. Sample Comparison Quantification Targeted / Quantitative Analysis Extract Data Exploratory Non-targeted Analysis Molecular Feature Extraction (MFE) and data pre-processing Multiple Reaction Monitoring Statistical analysis, Modelling and Clustering

31. Example Project • Project Aim: • Using a variety of techniques both targeted analysis as well as untargeted profiling to determine key components which are effected by the cancer • Two groups of patient types : • Healthy • Cancer • Three patients

32. Example Project

33. Example Project Patient 24 had a large amount of inflammation causing the control and cancer tissue to share a great deal of features similarities.

34. http://biosciences.exeter.ac.uk/facilities/spectrometry/ http://bio-massspeclocal.ex.ac.uk/ • Nick Smirnoff (Director of Mass Spectrometry) N.Smirnoff@exeter.ac.uk • Hannah Florance (MS Facility Manager) H.V.Florance@exeter.ac.uk • Venura Perera (Bioinformatics and Mathematical Support) V.perera@exeter.ac.uk

35. Numerical Dynamic Modeling γ BU Ak λ μ B C α AU E β • Reaction scheme: • AK: known substrate of B (can be removed if un-mapped • AU: Unknown substrate of B • B : Substrate to model • E : Enzyme(s) controlling the reaction • C : Known product of B • CU: Unknown product of B • BU : Unknown substrate of C CU

36. Example of Substrate-Product combo • Substrate-Product combo: • Switch profiles show delayed affect indicating possible reaction scheme • Profiles visually illustrate similarity γ BU Ak λ μ B C α AU E β CU

37. Anna Murray & Mike Weedon

38. Mike Weedon, PhD Lecturer in Bioinformatics and Statistics, Exeter Medical School, St Luke’s Campus M.N.Weedon@exeter.ac.uk Graduate in Biochemistry and Molecular Biology PhD in molecular genetics of type 2 diabetes, Peninsula Medical School Postdoc on genetics of complex traits, Peninsula Medical School Current research interests – genome-wide investigations of monogenic and polygenic traits Anna Murray, PhD Senior Lecturer in Human Genetics, Exeter Medical School, St Luke’s Campus A.Murray@exeter.ac.uk Graduate in Biology PhD in molecular biology of T cell receptor rearrangement in coeliac disease in Southampton Postdoc on population genetics of Fragile X syndrome in Salisbury/Southampton Current research interests – Genetics of female reproductive lifespan

40. Genome-wide SNP and expression array studies Whole exome/genome sequencing Statistical analysis of large datasets ENCODE and other projects to annotate non-coding genome Biological pathway analysis

41. Marcus Tuke

42. Supercomputer systems administrator Background Computer Science Graduate MSc Bioinformatics University of Exeter Medical School 8 months working on projects at the Wellcome Trust Centre for Human Genetics

43. Expertise I can offer Human Next Generation Sequence data processing and analysis Human RNA-Seq processing and analysis Computational expertise

44. Expertise I can offer Human Next Generation Sequence data processing and analysis Human RNA-Seq processing and analysis Computational expertise

45. Computational expertise • Help with projects that could benefit from expertise in: • Programming/scripting • Database/web development • Linux command line and cluster computing

46. Expertise I can offer Human Next Generation Sequence data processing and analysis Human RNA-Seq processing and analysis Computational expertise

47. Human 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 Genome Realign reads mis-aligned in genome due to indels Deletion SNP g>c heterozygote g c c g g g c

48. Expertise I can offer Human Next Generation Sequence data processing and analysis Human RNA-Seq processing and analysis Computational expertise

49. Human RNA-Seq processing and analysis Align RNA-Seq reads to Human Genome Transcriptome assembly Differential expression analysis

50. Research 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