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

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Page 1: Www.exeter.ac.uk/biomedicalhub Biomedical Informatics Hub

www.exeter.ac.uk/biomedicalhub

Biomedical Informatics Hub

Page 2: Www.exeter.ac.uk/biomedicalhub Biomedical Informatics Hub

WELLCOME TRUST ISSF BIOMEDICAL INFORMATICS

HUB

Dr Konrad Paszkiewicz

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Contents

Wellcome Trust ISSF• Background

Seed Corn Fund• Aims

Biomedical Informatics Hub• Purpose• Expertise• Resources• Training• Seminars• Project booking/Prioritisation• Sustainability

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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

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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

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Seed Corn Fund

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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)

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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 ([email protected])

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Biomedical Informatics Hub

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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

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Expertise

1. Bioinformatics• Medical - Marcus Tuke, Anna Murray & Mike Weedon

(Prof. Tim Frayling)• Bioscience - Dr Christine Sambles (Sequencing

Service)2. Metabolomics/Proteomics

• Dr Venura Perera (Dr Hannah Florance)3. Image analysis

• Dr Jeremy Metz (starting November) (Prof. Rob Beardmore)

4. Tomography and EM• TBC (Prof. Gero Steinberg)

5. Statistics• TBC (Prof. Tim Frayling)

6. Computational modelling/sensor-based networks• Dr Mahmood Javaid (Prof. Ed Watkins)

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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

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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

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Hub Training Courses

Training courses currently offered: 1. Amazon EC2 cloud computing

2. Unix & Perl

3. Short read genomics

4. Phylogenetics

5. Use of R statistical package

6. RNA-seq

New courses in 2013

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6. Seminars

Monthly seminars/workshop meetingsScope: bioinformatics, statistics, image

analysis, programming

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Submitting requests

You can approach Hub members informally for initial discussions about projects

If you’re unsure – email me

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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.

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Some screenshots.....

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Project proposal submission

bio-informaticsHub.ex.ac.uk

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Project proposal submission

bio-informaticsHub.ex.ac.uk

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Project proposal tracking

bio-informaticsHub.ex.ac.uk

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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

1. Seed Corn Fund projects2. Existing Wellcome Trust funded projects3. Wellcome Trust remit research4. Other research

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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

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Hub team presentations

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Ven Perera

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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

Page 27: Www.exeter.ac.uk/biomedicalhub Biomedical Informatics Hub

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

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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

My research interests

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Targeted / Quantitative Analysis

Multiple Reaction Monitorin

g

Statistical analysis,

Modelling and Clustering

SampleComparis

onQuantificationExploratory

Non-targeted Analysis

Extract Data

Molecular Feature

Extraction (MFE) and data pre-

processing

My WorkSmall Molecule analysis:

Untargeted profiling and Targeted quantification

Page 30: Www.exeter.ac.uk/biomedicalhub Biomedical Informatics Hub

Targeted / Quantitative Analysis

Multiple Reaction

Monitoring

Statistical analysis,

Modelling and Clustering

SampleComparison

QuantificationExploratory

Non-targeted Analysis

Extract Data

Molecular Feature

Extraction (MFE) and data pre-

processing

Page 31: Www.exeter.ac.uk/biomedicalhub Biomedical Informatics Hub

Example ProjectTwo groups of patient types :

• Healthy• Cancer

Three patients

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

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Example Project

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Example Project

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

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http://biosciences.exeter.ac.uk/facilities/spectrometry/

http://bio-massspeclocal.ex.ac.uk/

• Nick Smirnoff (Director of Mass Spectrometry) [email protected]

• Hannah Florance (MS Facility Manager) [email protected]

• Venura Perera (Bioinformatics and Mathematical Support) [email protected]

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Numerical Dynamic Modeling

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

Ak

AU

B

CU

C

E

BU

λ

α

β

μ

γ

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Example of Substrate-Product combo

Substrate-Product combo: • Switch profiles show delayed affect

indicating possible reaction scheme• Profiles visually illustrate similarity

Ak

AU

B

CU

C

E

BU

λ

α

β

μ

γ

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Anna Murray & Mike Weedon

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Mike Weedon, PhDLecturer in Bioinformatics and Statistics, Exeter Medical School, St Luke’s Campus

[email protected]

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, PhDSenior Lecturer in Human Genetics, Exeter Medical School, St Luke’s Campus

[email protected]

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

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Whole exome/genome sequencing

ENCODE and other projects to annotate non-coding genome

Genome-wide SNP and expression array studies

Biological pathway analysis

Statistical analysis of large datasets

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Marcus Tuke

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Background

Computer Science Graduate

University of Exeter Medical School

Supercomputer systems administrator

8 months working on projects at the Wellcome Trust Centre for Human Genetics

MSc Bioinformatics

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Expertise I can offer

Human Next Generation Sequence data processing and

analysis

Human RNA-Seq processing and

analysis

Computational expertise

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Expertise I can offer

Human RNA-Seq processing and analysis

Human Next Generation Sequence data

processing and analysis

Computational expertise

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Computational expertise

• Help with projects that could benefit from expertise in:

Programming/scripting

Database/web development

Linux command line and cluster computing

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Expertise I can offer

Human RNA-Seq processing and analysis

Computational expertise

Human Next Generation Sequence data processing and

analysis

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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

g

c

cgggc

Deletion SNP g>c heterozygote

Realign reads mis-aligned in genome due to indels

Page 48: Www.exeter.ac.uk/biomedicalhub Biomedical Informatics Hub

Expertise I can offer

Computational expertise

Human Next Generation Sequence data

processing and analysis

Human RNA-Seq processing and

analysis

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Human RNA-Seq processing and analysis

Align RNA-Seq reads to Human Genome

Transcriptome assembly

Differential expression analysis

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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

Page 51: Www.exeter.ac.uk/biomedicalhub Biomedical Informatics Hub

Whole-genome sequencing in the Inchianti Study

Ongoing projects

• A longitudinal study of aging from the Chianti region of Tuscany, Italy

• 1453 individuals have been followed up over 4 waves since 1998• Extensive phenotypic and biomedical information collected• Hundreds of circulating biomarkers (e.g. Interleukins, sex

hormones, vitamins) measured• RNA expression profiling in lymphocytes (Illumina 46K array)• Methylation profiling (450K array)• Already had the Illumina 550K SNP Chip genotyped• We are performing low-pass (median 7X) whole genome

sequencing on 680 of these individuals

http://www.inchiantistudy.net

RNA-Seq whole-transcriptome assembly and analysis

• Assemble transcriptomes for 3 primary human microvascular endothelial cells

• 2 treated with cathepsin L and D respectively, and 1 control• Analyse whether there are any differences in expression of RNA between

two treatments and control

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Christine Sambles

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Jeremy Metz

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JEREMY METZ, PHD

PhD: Quantum computing - theory & simulations Imperial College London

Postdoc: Biological image analysis & cellular modelling Einstein College of Medicine, NY

Page 56: Www.exeter.ac.uk/biomedicalhub Biomedical Informatics Hub

Research Interests

• Image processing and computer vision applied to biological systemso Object segmentation o Tracking in range of dynamical scenarioso Quantitative analysis

• Modelling biological systems - analytical and numerical approacheso Monte-carlo simulationso Integration of data and insight from multiple scales

of inquiry, e.g. AFM, single cell analysis, high throughput screening

Page 57: Www.exeter.ac.uk/biomedicalhub Biomedical Informatics Hub

Skills and Expertise

• Python, C++, Java, Matlab

• Image processingo Matlab - image processing toolkito Python - Scipy and OpenCV bindingso Java - ImageJ plugins

• Simulationo C/C++ for fast low-level routineso Python as "glue" code and visualization

• Linux, shell scripting, Oracle Grid Engine

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Past Projects - Image processing

Object 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 formalism

Page 59: Www.exeter.ac.uk/biomedicalhub Biomedical Informatics Hub

Simulation

Biological 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 illumination

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How 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?

Experiments Extract data

Model, Simulation

Theory

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Mahmood Javaid

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Area of expertise:• Computational Modelling• Sensor-based Networks and Embedded

Systems• High Performance Computing• Software Development

MAHMOOD JAVAID PHD COMPUTER SCIENCEEXPERIMENTAL OFFICER- RESEARCH COMPUTINGWELLCOME TRUST BIOMEDICAL INFORMATICS HUB

Page 63: Www.exeter.ac.uk/biomedicalhub Biomedical Informatics Hub

Computational Modelling

Agent-based modelling using Agent-based simulation frameworks such as FLAME and SWARM

Benefits: Close association between the model entities and

the real-world agents Heterogeneous agents within an environment Interaction between the agents through message

passing Potential to uncover emergent behaviours Possibility of multi-scale modelling

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Some examples

Prospecting asteroid belt

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Hypothesis testing

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Economics and Systems biological applications of ABM

Eurace project

(Dept. of Computer Science, University of Sheffield.)

System Understanding of Microbial Oxygen Responses (SUMO)

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Sensor-based networks, embedded systems

Involving 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

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Sensory augmentation device

In 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.

Page 69: Www.exeter.ac.uk/biomedicalhub Biomedical Informatics Hub

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 them—stroking with the fingertips to investigate texture, for instance, or palpating to investigate shape.

Active Touch

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Inspired from biological and biomimetics

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Physical Components

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First Prototype

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High Performance Computing

Agent-based models running on Linux

HPC clusters

Administration of Linux HPC cluster

Publishing legacy applications running

on Linux clusters using web-services

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Software Development

Desktop applications for Linux and

Windows platforms including Matlab

Web-based applications and publishing

legacy systems using web-services

Mobile Operating System applications

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Online Depression and Mood Disorder Screener

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www.exeter.ac.uk/biomedicalhub

Thanks for listening.....