Accelerated discovery of functional non-coding genomic variation using single molecule real-time (SMRT) sequencing.

Lead Research Organisation: University of Exeter
Department Name: University of Exeter Medical School

Abstract

The last decade has seen tremendous advances in our understanding about the role of genetic variation in health and disease, driven largely by developments in technology for sequencing the genome. Genes involved in a spectrum of debilitating disorders and health-related traits have been identified, including many by researchers at the University of Exeter Medical School, and these discoveries are starting to directly impact upon clinical practice. Despite this success, however, many regions of the genome remain hidden to contemporary first- and second-generation sequencing approaches. These include highly complex stretches of repetitive DNA and regions harbouring other types of genetic variation such as deletions and duplications. Furthermore, because the sequencing reads generated by current approaches are relatively short, they cannot be used to examine the long-distance relationships between more distal variants, nor explore the extent to which different genes are expressed in different versions in health and disease. Finally, most focus in disease genetics has been on regions of the genome that actually encode specific genes, ignoring the role of regulatory variation occurring outside of these regions. Of note, current sequencing approaches cannot be used to directly detect the presence of non-sequence-based epigenetic modifications and explore their role in disease. In this application we are requesting funds to support the acquisition of "third generation" sequencing technology, which will enable us to fully characterise genomic complexity. We are also requesting funds to support the high-performance computing infrastructure needed to store and analyse this complex data. Our aim is to advance genomics research into diabetes, neurological and other medical conditions by defining functional genetic and epigenetic variation in non-coding regions of the human genome.

Technical Summary

We are requesting funds to develop our genomic sequencing infrastructure, primarily through the acquisition of a Pacific Biosciences single molecule real-time (SMRT) sequencing system, making us one of only a handful of institutes in Europe to have such capability. This system will enable us to assay, identify and analyse regions of the genome hidden from current methods for gene discovery, and facilitate research into the functional mechanisms involved in disease. The Pacific Biosciences RS II SMRT Sequencing System provides the highest consensus accuracy and longest read lengths of any sequencing technology; current average read-lengths are >8.5kb (with a maximum of ~50kb). SMRT sequencing will facilitate advances in disease characterisation, stratification and diagnosis via its unique utility for de novo assembly across highly complex regions of the genome, targeted re-sequencing, long-range phasing of genetic variation, and epigenomic analysis via the direct allele-specific detection of modified DNA bases. We will also develop our High-Performance Computing/Informatics Infrastructure to enable the storage, analysis, alignment, and assembly of SMRT sequencing data. This infrastructure investment will enable the world-leading genetic and epigenetic research groups at the University of Exeter Medical School to further develop their innovative program of clinical genomic research in human disease, with a specific focus on diabetes and neurological phenotypes.

Planned Impact

In addition to other scientists (especially other and research groups investigating the role of genetics in diabetes and neurological diseases) the data generated using the new sequencing infrastructure has the potential to impact on a number of other beneficiaries. These include patients, the pharmaceutical industry, health service providers, and academic groups investigating the causes of other disease phenotypes and functional genomics. Existing genetics research by Exeter groups has already made significant impact in terms of understanding the causes of disease and the mechanisms behind disease progression (see description in the Case for Support), with tangible patient benefit. For example, Professor Hattersley's group discovered that patients with neonatal diabetes caused by K-ATP channel mutations demonstrate a remarkable improvement in glycaemic control when sulphonylurea tablets replace insulin injections. Quality of life has also been improved for many patients with maturity onset diabetes of the young (MODY) who have either stopped treatment or transferred from insulin to sulphonylureas as a consequence of their genetic diagnosis. The ability of SMRT sequencing to interrogate regions of the genome hidden from second generation sequencing, in addition to epigenetic and transcriptomic variation, will identify additional pathways to disease that we hope to have similar impact on clinical diagnosis, prognosis, and treatment.

Publications

10 25 50
 
Description ARUK Project Grant
Amount £433,549 (GBP)
Funding ID ARUK-PG2018B-016 
Organisation Alzheimer's Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2019 
End 02/2022
 
Description Accelerating genetic research in Exeter with the Illumina NovaSeq 6000 DNA Sequencing System
Amount £616,706 (GBP)
Funding ID 218247/Z/19/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2019 
End 10/2020
 
Description CASE STUDENTSHIP
Amount £100,000 (GBP)
Funding ID MR/P016227/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 08/2017 
End 09/2021
 
Description Development of software to model multi-modal genomic data as an integrated system: application to understanding the gene regulatory landscape
Amount £823,688 (GBP)
Funding ID EP/V052527/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 11/2021 
End 10/2026
 
Description Establishment of a single cell isolation platform for identification of heavy and light1 chains in the antibody repertoire using PacBio sequencing" MRC Proximity to Discovery Grant, University of Exeter (S.Pagliara & K.Paszkiewicz, £137,427
Amount £137,427 (GBP)
Organisation University of Exeter 
Sector Academic/University
Country United Kingdom
Start 03/2016 
End 12/2016
 
Description NARSAD YOUNG INVESTIGATOR [EILIS HANNON]
Amount $70,000 (USD)
Organisation Brain & Behaviour Research Foundation 
Sector Charity/Non Profit
Country United States
Start 01/2018 
End 12/2019
 
Description Research grant
Amount £1,012,743 (GBP)
Funding ID MR/R005176/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2018 
End 12/2020
 
Description SFARI Research Grant
Amount $975,000 (USD)
Organisation Simons Foundation 
Sector Charity/Non Profit
Country United States
Start 02/2018 
End 02/2021
 
Description University of Exeter - SMRT Pump-priming funds
Amount £50,000 (GBP)
Organisation University of Exeter 
Sector Academic/University
Country United Kingdom
Start 01/2016 
End 07/2016
 
Title Fluorescence-activated nuclei sorting (FANS) on human post-mortem cortex tissue enabling the isolation of distinct neural cell populations for multiple omic profiling 
Description Increased understanding of the functional complexity of the genome has led to growing recognition about the role of epigenetic/transcriptional variation in health and disease. Current analyses of the human brain, however, are limited by the use of "bulk" tissue, comprising a heterogeneous mix of different neural cell types. Because epigenetic processes play a critical role in determining cell type-specific patterns of gene regulation it is important to consider cellular composition in regulatory genomic studies of human post-mortem tissue, and there is a need for methods to purify populations of specific cell-types. Furthermore, the valuable nature of human post-mortem tissue means it is important to use methods that maximize the amount of genomic data generated on each sample. This protocol describes a method that uses fluorescence-activated nuclei sorting (FANS) to isolate and profile nuclei from multiple different human brain cell-types from frozen post-mortem tissue. This protocol can be used to robustly purify populations of neuronal (NeuN+ve), oligodendrocytes (SOX10+ve), microglia (IRF8+ve) and other glial origin nuclei (NeuN-ve/SOX10-ve/IRF8-ve) from adult post-mortem frozen brain, with each tissue sample yielding purified populations of nuclei amenable to simultaneous analysis of i) DNA modifications (via bisulfite sequencing / array), ii) histone modifications (via CUT&Run-seq), iii) open chromatin analysis (via ATAC-seq), and iv) gene expression (via RNA-seq). 
Type Of Material Technology assay or reagent 
Year Produced 2020 
Provided To Others? Yes  
Impact This method for isolating purified nuclei populations from human cortex is being widely used by us and other groups to undertake work into the genomic underpinnings of disease. 
URL https://www.protocols.io/view/fluorescence-activated-nuclei-sorting-fans-on-huma-bmh2k38e.html
 
Title Genetics of DNA methylation Consortium mQTL dataset 
Description Cis and trans meta-analysis results from genome-wide scans of 420,509 DNA methylation sites 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
Impact Therse data are being widely used by the wider research community. 
URL http://mqtldb.godmc.org.uk/
 
Title GitHub code for genomic studies on purified brain cell types 
Description We have made all our analysis code available to other researchers on GitHub. 
Type Of Material Computer model/algorithm 
Year Produced 2020 
Provided To Others? Yes  
Impact Our code means that other groups can replicate our findings and apply our methods to their own projects. 
URL https://github.com/ejh243/BrainFANS
 
Title Human and Mouse Brain Iso-seq and RNA-Seq 
Description Visual database of brain isoforms from human and mouse cortex. 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
Impact The database has been accessed by multiple research groups and we have instigated a number of new collaborations from these data. 
URL https://genome.exeter.ac.uk/build/index.html
 
Title Human and mouse cortex isoform database 
Description tive splicing is a post-transcriptional regulatory mechanism producing multiple distinct mRNA molecules from a single pre-mRNA. Alternative splicing has a prominent role in the central nervous system, impacting neurodevelopment and various neuronal functions as well as being increasingly implicated in brain disorders including autism, schizophrenia and Alzheimer's disease. Standard short-read RNA-seq approaches only sequence fragments of the mRNA molecule, making it difficult to accurately characterize the true nature of transcript isoform diversity. In this study, we used long-read isoform sequencing (Iso-Seq) to generate full-length cDNA sequences and map transcript diversity in the human and mouse cortex. We identify widespread isoform diversity amongst expressed genes in the cortex, including many novel transcripts not present in existing genome annotations. Alternative splicing events were found to make a major contribution to isoform diversity in the cortex, with intron retention being a relatively common event associated with nonsense mediated decay and reduced expression. Of note, we found evidence for transcription from novel (unannotated genes) and fusion events between neighbouring genes. Although global patterns of isoform diversity were found to be generally similar between human and mouse cortex, we identified some notable exceptions. We also identified striking developmental changes in isoform diversity, with differential transcript usage between adult and fetal cortex. Finally, we found evidence for extensive isoform diversity in genes associated with autism, schizophrenia and Alzheimer's disease. Our data confirm the importance of alternative splicing in the cortex, dramatically increasing transcriptional diversity and representing an important mechanism underpinning gene regulation in the brain. We provide this isoform level data as a resource to the scientific community. 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
Impact This is the largest database of cortex isoforms generated using long-read sequencing. The database has been widely accessed and used by other researchers in the field. 
URL http://genome.exeter.ac.uk/BrainIsoforms.html
 
Description Collaboration with Eli Lilly & Co 
Organisation Eli Lilly & Company Ltd
Country United Kingdom 
Sector Private 
PI Contribution We have begun working extensively with collaborators at Eli Lilly on projects spanning neuroscience, genomics, dementia and schizophrenia. We now have a joint grant funded and two CASE PhD students.
Collaborator Contribution Access to transgenic models and resources for research studies Access to laboratory facilities and compounds Co-funding of students
Impact We have submitted several grant applications, and have been funded by ARUK to undertake a joint project on rodent models of neuropathology. We have successfully applied for funding for two CASE PhD students [one MRC, one BBSRC]
Start Year 2016
 
Description Collaboration with Gloria Sheynkman group 
Organisation University of Virginia Medical Center
Country United States 
Sector Hospitals 
PI Contribution We are collaborating on validation of protein changes related to novel gene transcripts identified in human brain
Collaborator Contribution They are providing expertise and data to help us compare RNA and protein isoforms
Impact We are working on a joint publication.
Start Year 2021
 
Description Collaboration with Pinto group, Mount Sinai School of Medicine, New York 
Organisation Icahn School of Medicine at Mount Sinai
Country United States 
Sector Academic/University 
PI Contribution We are working with the group of Dalila Pinto to create a database of isoform diversity and alternative splicing in the human and mouse brain. We have generated fetal cortex Pacific Biosciences Iso-Seq data as part of our MRC funding and mouse cortex iso-seq data as part of our ARUK funding.
Collaborator Contribution Our partner group have generated complementary datasets, including data on adult cortex samples.
Impact We are currently finalising a publication for submission.
Start Year 2019
 
Description Collaboration with The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPsych) and Minerva consortia 
Organisation Aarhus University
Country Denmark 
Sector Academic/University 
PI Contribution We are working extensively on DNA methylation analyses of dried blood spots collected at birth to identify molecular biomarkers of prenatal exposures and risk for developing psychiatric illness.
Collaborator Contribution We have played an integral role in analysing and generating DNAS methylation data from Danish blood spot data. I am a member of the Scientific Advisory Board for iPsych.
Impact We have been involved in several collaborative research projects, with several papers already published and other in preparation.
Start Year 2016
 
Description Collaboration with The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPsych) and Minerva consortia 
Organisation Icahn School of Medicine at Mount Sinai
Country United States 
Sector Academic/University 
PI Contribution We are working extensively on DNA methylation analyses of dried blood spots collected at birth to identify molecular biomarkers of prenatal exposures and risk for developing psychiatric illness.
Collaborator Contribution We have played an integral role in analysing and generating DNAS methylation data from Danish blood spot data. I am a member of the Scientific Advisory Board for iPsych.
Impact We have been involved in several collaborative research projects, with several papers already published and other in preparation.
Start Year 2016
 
Description Collaboration with Understanding Society cohort 
Organisation University of Essex
Department Institute for Social and Economic Research, Essex
Country United Kingdom 
Sector Academic/University 
PI Contribution We have worked with Professor Kumari and Professor Schalkwyk to generate an extensive DNA methylation resource in the Understanding Society cohort. This resource is available to other researchers and is being used in many ongoing projects.
Collaborator Contribution They provided us with DNA samples for profiling from ~4500 individuals. This represents one of the largest DNA methylation resources available.
Impact 1/ a DNA methylation data resource that is being used by groups across the world 2/ multiple publications coauthored by us and other groups
Start Year 2019
 
Description Collaboration with Understanding Society cohort 
Organisation University of Essex
Department Institute for Social and Economic Research, Essex
Country United Kingdom 
Sector Academic/University 
PI Contribution We have worked with Professor Kumari and Professor Schalkwyk to generate an extensive DNA methylation resource in the Understanding Society cohort. This resource is available to other researchers and is being used in many ongoing projects.
Collaborator Contribution They provided us with DNA samples for profiling from ~4500 individuals. This represents one of the largest DNA methylation resources available.
Impact 1/ a DNA methylation data resource that is being used by groups across the world 2/ multiple publications coauthored by us and other groups
Start Year 2019
 
Description 2017 WORKSHOP ON GENOMICS, CESKY KRUMLOV 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact The Workshop on Genomics was developed in response to the increasing demand for training on how to effectively analyze and manage data generated by modern sequencing technologies. The Workshop curriculum includes extensive coverage of fundamental techniques required of all studies utilizing modern sequence data. This includes management and modification of modern sequence data files, using the Unix command-line and editors to manipulate large data files, assembly and best practices for sequence data generation, management and analysis. The second-half of the Workshop is devoted to specific sub-disciplines within the genomic sciences. While these topics may change from year-to-year, efforts are made to devote significant amounts of time to techniques being used widely in the field (e.g. transcriptomics, genome assembly, metagenomics, population genomics).
Year(s) Of Engagement Activity 2017
URL http://evomics.org/workshops/workshop-on-genomics/2017-workshop-on-genomics-cesky-krumlov/
 
Description 2018 Paul Janssen Lecture at IoPPN 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The Paul Janssen Lecture has been a regular feature of the academic calendar at the Institute of Psychiatry, Psychology & Neuroscience for nearly 20 years.
Lecturers are chosen on the basis of their global eminence in the field of neuroscience with a focus on schizophrenia. The annual lecture is named in honour of Belgian pharmacologist Paul Janssen (1926-2003) noted for discovering various drugs important to psychiatry, such as haloperidol, and who founded Janssen - the pharmaceutical company which sponsors the event.
Year(s) Of Engagement Activity 2018
URL https://www.kcl.ac.uk/ioppn/news/special-events/paul-janssen-lecture
 
Description Brain Awareness Week Public Lecture 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact As part of the inaugural Exeter Brain Awareness Week, I gave a public (lay) presentation on our research into genomics of schizophrenia.
Year(s) Of Engagement Activity 2018
URL http://www.exeter.ac.uk/news/events/details/index.php?event=8040
 
Description Brain Prize meeting - Lundbeck Foundation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I was invited to give a presentation at the Brain Prize meeting arranged by the Lundbeck Foubdation. I gave an overview of our work into the genomics of brain disorders. I have been subsequently approached by several groups with requests for data and collaboration.
Year(s) Of Engagement Activity 2021
URL https://lundbeckfonden.com/en/the-brain-prize
 
Description British Society for Research on Aging Meeing - Keynote Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Professor Mill presented latest findings from brain genomics studies in context of ageing.
Year(s) Of Engagement Activity 2017
URL http://bsra.org.uk/bsra-2017-university-exeter/
 
Description Celebrating Diversity in Science Virtual Conference - Oral Presentation: Heterogeneity in purified neural populations: implications for post-mortem genomic studies. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact One of our team members gave a presentation at the Celebrating Diversity in Science Virtual Conference. This had a large impact, not only focused on scientific results but also discussing diversity in science.
Year(s) Of Engagement Activity 2020
URL https://www.facebook.com/events/d41d8cd9/celebrating-diversity-in-science-virtual-conference/1922678...
 
Description Cold Spring Harbor Laboratories: Workshop on Autism Spectrum Disorders - Foetal Brain Development and Neuropsychiatric Disease 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact We presented our work on gene regulation in human brain development at this workshop in which attendees develop their knowledge of the field of research into ASD and the implications on clinical output. Wide range of experience from attendees, from various backgrounds of research. Attendees share their research and develop networking connections.
Year(s) Of Engagement Activity 2019
URL https://meetings.cshl.edu/autism19
 
Description Epigenomic and transcriptional signatures of progressive neuropathology in transgenic models of Alzheimer's disease - Oral presentation at the Wellcome Trust Epigenoics of Common Diseases meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact We presented our first major findings from our study of gene regulation in mouse models of Alzheimer's disease pathology.There was considerable interest in this work from the audience with many questions and requests for additional information.
Year(s) Of Engagement Activity 2019
URL https://coursesandconferences.wellcomegenomecampus.org/register/conferences/form1.aspx?e=771
 
Description Epigenomics of Common Diseases Meeting - Wellcome Trust 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Our group presented a series of posters and talks on data generated by our MRC funding.
Year(s) Of Engagement Activity 2017
URL https://coursesandconferences.wellcomegenomecampus.org/events/item.aspx?e=638
 
Description Evaluation of nanopore sequencing for epigenetic epidemiology: a comparison with DNA methylation microarrays 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Gave a presentation on our long-read isoform sequencing approaches to explore alternative splicing in the brain
Year(s) Of Engagement Activity 2021
 
Description Feature article on our research in British Neuroscience Association (BNA) Newsletter 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact The BNA interviewed me, and wrote a feature article on our work.
Year(s) Of Engagement Activity 2016
URL https://www.bna.org.uk/publications/bna-bulletin/
 
Description Functional characterisation of GWAS loci using epigenetic editing - Oral Presentation at Wellcome Trust Epigenomics of Common Disease Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact We presented our work on epigenetic editing of schizophrenia candidate genes nominated from our MRC-funded project. The talk instigated considerable debate and interest from novel collaborators.
Year(s) Of Engagement Activity 2019
URL https://coursesandconferences.wellcomegenomecampus.org/register/conferences/form1.aspx?e=771
 
Description International Molecular Pathology Symposium - Edinburgh 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Professor Mill gave an invited talk at the 2017 International Molecular Pathology Symposium. He discussed current advances in using genomics in molecular pathology. There was considerable discussion following the even and several new collaborations established.
Year(s) Of Engagement Activity 2017
URL https://www.ed.ac.uk/centre-genomic-medicine/news-events/news-2017/international-molecular-pathology...
 
Description Invited Lecture - Astex Pharmaceuticals. Global Lecture Series 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Invited to give an update of our research to a wide audience online.
Year(s) Of Engagement Activity 2021
URL https://astx.com/
 
Description Invited Lecture - Radboud University, Nijmegen 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact Professor Mill was invited to give a lecture at Radboud University in Nijmegen, The Netherlands; hosted by Barbara Franke. He presented an overview of our work on epigenetic analyses of mental health including schizophrenia. He also gave an overview of novel genomic sequencing technologies. The lecture sparked considerable discussion and several new potential collaborations.
Year(s) Of Engagement Activity 2017
URL http://www.ru.nl/english/people/franke-b/
 
Description Invited seminar - Roche Pharmaceuticals, pRED, Neurosciences & Rare Disease. Invited Seminar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Online virtual seminar to the pRED department at Roche.
Year(s) Of Engagement Activity 2021
 
Description Invited seminar at Department of Psychiatry, University of Oxford 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact I gave an invited seminar to researchers at the University of Oxford Departmenty of Psychiatry. I presented an overview of our work on the genomics of schizophrenia and dementia. Following this seminar I visited the department in person, met with several researchers and discussed novel collaborations.
Year(s) Of Engagement Activity 2020
URL https://www.psych.ox.ac.uk/
 
Description Invited seminar at Roche Pharma 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact I gave an invited seminar on genomics to the neuroscience genomics group at Roche. I presented an overview of our work and how this might inform drug discovery in the future.
Year(s) Of Engagement Activity 2021
URL https://www.roche.com/
 
Description Invited seminar at the UCL Dementia Research Institute 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact I gave an invited seminar to the UK Dementia Research Institute at UCL where I presented our research into the genomic basis of dementia and schizophrenia. As a result of this seminar, I have established several novel collaborations and disseminated information about our data resources to the wider community.
Year(s) Of Engagement Activity 2020
URL https://www.ucl.ac.uk/uk-dementia-research-institute/
 
Description Invited seminar for the Imperial College London Dementia Research Institute 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact I gave an invited seminar to the UK Dementia Research Institute where I presented our research into the genomic basis of dementia and schizophrenia. As a result of this seminar, I have established several novel collaborations and disseminated information about our data resources to the wider community.
Year(s) Of Engagement Activity 2020
URL https://www.imperial.ac.uk/dementia-research-institute/seminars--events/2019-20-seminars/
 
Description Invited speaker at the "Epigenetics in the Nervous System" meeting in Stockholm 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I gave an invited presentation at this international meeting sponsored by Abcam. There was considerable discussion and interest in our work, and several new collaborative opportunities arising from this are being explored.
Year(s) Of Engagement Activity 2018
URL http://docs.abcam.com/pdf/events/stockholm-2018-program.pdf
 
Description Invited speaker at the 2018 International Human Epigenome Consortium (IHEC) meeting in Hong Kong 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I was an invited speaker at the 2018 IHEC meeting which brings together researchers from around the world working on epigenomics. I presented our ongoing work to leaders in the field and established new collaborations with other international groups.
Year(s) Of Engagement Activity 2018
URL http://ihec-epigenomes.org/news-events/hong-kong-2018/
 
Description Invited speaker at the virtual event Epigenetics - The Full Picture from Illumina International. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited presentation on our epigenomics work for Illumina seminar series
Year(s) Of Engagement Activity 2021
 
Description Invited talk - Genome Institute of Singapore 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Professor Mill gave a presentation and established new collaborations at GIS and other institutions in Singapore.
Year(s) Of Engagement Activity 2017
URL http://www.gis.a-star.edu.sg
 
Description Isoform diversity in the human cortex - SFARI Annual Meeting, New York 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I presented our work on RNA isoform diversity at the Simons Foundation in New York. This stimulated considerable interest, and interaction with research groups with whom we are now collaborating.
Year(s) Of Engagement Activity 2019
URL https://www.sfari.org/events/
 
Description Long-reads, single-cells and cream teas -- Third-generation sequencing meeting / workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact We organised a day workshop and conference to launch our MRC Clinical Infrastructure project. It was a great success with atendees from across the UK and international speakers. Programme below:
1st September 2015, University of Exeter, U.K.

Location: RILD Building, RD&E Hospital (directions here).

To celebrate the launch of our MRC Clinical Infrastructure and our new Pacific Biosciences instrument, we'd like to invite you to a special one-day meeting.

09:00 - 09:45 Tea/coffee

09:45 - 10:00 Welcome

10:00 - 10:30 Introduction to PacBio, Steve Picton Pacific Biosciences

10:30 - 11:00 Introduction to Oxford Nanopore, James Brayer/Oliver Hartwell Oxford Nanopore Technologies

11:15 - 12:00 18 months of PacBio sequencing - John Kenny, Liverpool Centre for Genomic Research

12:00 - 13:00 Lunch

13:00 - 14:00 Single cell genomics at Joint Genome Institute, Tanja Woyke

14:00 -14:45 Evolutionary genomics with PacBio - Alistair Darby, University of Liverpool

14:45 - 15:30 Clinical and bacterial applications of long-read sequencing - Nick Loman, University of Birmingham

15:30 - 16:15 Tea/coffee

16:15 - 17:15 Genomics at the New York Genome Centre, Mike Zody

17:15 - 18:15 Genome Sciences at University Washington, School of Medicine, Evan Eichler

Followed by an evening meal at the Cosy Club, Exeter.
Year(s) Of Engagement Activity 2015
URL http://sequencing.exeter.ac.uk/long_reads_and_cream_teas/
 
Description MRC Expert Group Meeting on Human Brain Research 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact We discussed optimal approaches for using human brain tissue in research
Year(s) Of Engagement Activity 2017
 
Description Meta-analysis of epigenome-wide association studies in Alzheimer's disease highlights 220 differentially methylated loci across cortex - Oral Presentation at Wellcome Trust Epigenomics of Common Diseases meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact We presented our findings from a large EWAS meta-analysis of Alzheimer's disease. We are assessing parallel changes at the same loci in our study of regulatory genomic changes in mouse models of neuropathology, funded by ARUK. The presentation sparked considerable interest with many questions and opportunities for novel collaborations.
Year(s) Of Engagement Activity 2019
URL https://coursesandconferences.wellcomegenomecampus.org/register/conferences/form1.aspx?e=771
 
Description Multiple presentations and posters at the World Congress of Psychiatric Genetics in Glasgow 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Our group had several presentations at the 2018 WCPG meeting, disseminating results from our work into the genomics of schizophrenia. There was considerable interest in our data and we interacted with collaborators on the projects.
Year(s) Of Engagement Activity 2018
URL https://wcpg2018.org
 
Description Multiple presentations at World Congress of Psychiatric Genetics 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact We presented multiple findings at the World Congress of Psychiatric Genetics, including talks on microRNAs in schizophrenia, epigenetic analyses in schizophrenia, and novel methods for profiling purified nuclei populations. Our work reached an international audience and several collaborations on future projects.
Year(s) Of Engagement Activity 2020
URL https://ispg.net/wcpg-2020/
 
Description Multiple presentations at the Wellcome Trust Epigenomics of Common Diseases meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact We presented our data in multiple presentations at the 2020 Epigenomics of Common Diseases meeting. This enabled us to disseminate our work to a wide scientific audience and also help foster novel collaborations.
Year(s) Of Engagement Activity 2020
URL https://coursesandconferences.wellcomegenomecampus.org/register/conferences/form1.aspx?e=808
 
Description Oral presentation at ARUK Conferences, Harrogate, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited talk at the annual ARUK meeting in Harrogate discussing my teams research into the epigenetics of Alzheimer's disease.
Year(s) Of Engagement Activity 2019
URL https://www.alzheimersresearchuk.org/for-researchers/research-conference-2020/
 
Description Oral presentation at Wellcome Trust Epigenomics of Common Diseases meeting - Pleiotropic effects of trait-associated genetic variation on DNA methylation: Utility for refining GWAS loci 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact We presented our work on fine-mapping schizophrenia risk loci using epigenetic annotations. The talked sparked questions and considerable positive feedback on our work.
Year(s) Of Engagement Activity 2019
URL https://coursesandconferences.wellcomegenomecampus.org/register/conferences/form1.aspx?e=771
 
Description PacBio Global Summit - Using Iso-Seq to uncover AD-associated splicing variants in mouse model of tau pathology and human cortex 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A team member was invited to join this panel discussion on long-read sequencing for identifying novel isoforms / transcripts. This had a very broad international audience and resulted in several new collaborations.
Year(s) Of Engagement Activity 2020
URL https://events.pacb.com/global-summit
 
Description Pacific Biosciences Long Read Sequencing - Exeter Engagement Day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact We organised a day workshop in collaboration with Pacific Biosciences to promote long-read sequencing infrastructure in Exeter. There were numerous end-user presentations and discussions about novel applications and sequencing approaches.
Year(s) Of Engagement Activity 2019
URL http://sequencing.exeter.ac.uk
 
Description Presentation at Academy of Medical Sciences meeting: The developing brain in health and disease - Molecular profiling of discrete cellular populations in post mortem human cortex 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact We presented our method for isolating nuclei from specific neural cell populations from human cortex developed in our MRC project grant. This two day meeting hosted by the Academy of Medical Sciences highlighted the latest advances in the field and provided a unique space for researchers across disciplines to discuss the challenges and priorities for neurodevelopmental research.
Year(s) Of Engagement Activity 2019
URL https://acmedsci.ac.uk/more/news/understanding-brain-development-what-next-for-research
 
Description Presentation at INSAR meeting, Montreal, Canada. Epigenetic pathways to neurodevelopmental phenotypes. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I was an invited speaker at a workshop on gene regulation in the brain in neurodevelopmental phenotypes (autism, schizophrenia). I presented work to a large audience on our findings related to gene expression, epigenetics and isoform diversity in the human cortex. The meeting involved teams from across the world and resulted in ongoing collaborations with researchers at Mount Sinai School of Medicine in New York.
Year(s) Of Engagement Activity 2019
URL https://insar.confex.com/insar/2019/webprogram/start.html
 
Description Presentation on long-read genomics: 2016 Workshop on Genomics, Cesky Krumlov 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The Workshop on Genomics was developed in response to the increasing demand for training on how to effectively analyze and manage data generated by modern sequencing technologies. The Workshop curriculum includes extensive coverage of fundamental techniques required of all studies utilizing modern sequence data. This includes management and modification of modern sequence data files, using the Unix command-line and editors to manipulate large data files, assembly and best practices for sequence data generation, management and analysis. The second-half of the Workshop is devoted to specific sub-disciplines within the genomic sciences. While these topics may change from year-to-year, efforts are made to devote significant amounts of time to techniques being used widely in the field (e.g. transcriptomics, genome assembly, metagenomics, population genomics).
Year(s) Of Engagement Activity 2016
URL http://evomics.org/workshops/workshop-on-genomics/2016-workshop-on-genomics-cesky-krumlov/
 
Description Presentations at Alzheimer's Research UK 2022 meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact We presented several presentations detailing results from our research projects.
Year(s) Of Engagement Activity 2022
 
Description Presentations at the Wellcome Trust Genomics of Brain Disorders Meeting, Cambridge 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact We had a series of presentations - oral talks and posters - presented on our work at this international meeting on the genomics of brain disorders.
Year(s) Of Engagement Activity 2018
URL https://coursesandconferences.wellcomegenomecampus.org/our-events/genomics-of-brain-disorders-2018/
 
Description Seminar at OHSU in Portland, USA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact I was invited to give a seminar at OHSU in Portland where I discussed our work to medics and researchers. I discussed ongoing research into psychiatric epigenetics and established several new collaborations.
Year(s) Of Engagement Activity 2018
 
Description Symposium at 13th World Congress of Biological Psychiatry, Copenhagen 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Professor Mill was co-chair and a presenter at the ISBP meeting.
Year(s) Of Engagement Activity 2017
URL http://www.wfsbp-congress.org/former-congresses/highlights2017.html
 
Description Training seminars in genomics / bioinfotrmatics 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact The Bioinformatics Support Service (EXBiSS) offers a number of advanced training courses aimed at developing the skills necessary to handle large scale high-throughput datasets from sequencing, mass-spectrometry and ecology.
The course are available to PhD students, post-doctoral researchers and staff. As part of the current MRC funded grant, we established training in genomics and sequencing analysis.
Year(s) Of Engagement Activity 2015,2016
URL http://www.exeter.ac.uk/biomedicalhub/training/
 
Description Two selected oral presentations at the Wellcome Trust Epigenomics of Common Diseases meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact We had two platforms presenting work from this project at the Wellcome Trust Epigenomics of Common Diseases meeting.
Year(s) Of Engagement Activity 2016
URL https://coursesandconferences.wellcomegenomecampus.org/events/item.aspx?e=594
 
Description UK Pharmacogenetics and Stratified Medicine - Open Meeting - Invited Talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Professor Mill gave an invited lecture on how epigenetic epidemiology might inform pharmacokinetic studies. There was considerable interest and many questions.
Year(s) Of Engagement Activity 2017
URL http://www.uk-pgx-stratmed.co.uk
 
Description Workshop on Schizophrenia and Related Disorders - Cold Spring Harbor 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact I taught on the Cold Spring Harbor Schizophrenia Workshop as an invited lecturer. This involved small-group teaching to leading postdocs and PhD students selected form around the world. The students were enthused about genomics in schizophrenia and there was very positive feedback.
Year(s) Of Engagement Activity 2018
URL http://meetings.cshl.edu/schizophrenia18
 
Description XXV World Congress of Psychiatric Genetics, Orlando 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact We had multiple presentations at the 2017 WCPG meeting. We networked extensively with collaborators and established several new projects.
Year(s) Of Engagement Activity 2017
URL https://wcpg2017.org