Regulatory genomic profiling in schizophrenia
Lead Research Organisation:
UNIVERSITY OF EXETER
Department Name: Institute of Biomed & Clinical Science
Abstract
Schizophrenia is a severe psychiatric disorder, characterised by psychotic symptoms, delusions and hallucinations, disorganisation, dysfunctional affective responses, and altered cognitive functioning. The social and economic consequences of schizophrenia are severe, eclipsing those of many other illnesses. With a lifetime prevalence rate of ~1%, schizophrenia contributes significantly to the global burden of disease, ranking among the top ten causes of disability in developed countries worldwide. Although the symptoms of schizophrenia do not typically appear until late adolescence or early adulthood, evidence from neuroimaging, neuropathology and epidemiological studies indicate that it is a neurodevelopmental disorder, influenced by risk factors with effects during prenatal development of the brain. To date, however, the neurobiological mechanisms underlying the disorder remain largely undefined, and molecular evidence linking neurodevelopmental dysfunction to schizophrenia is limited.
Studies into the causes of schizophrenia have focused on describing the genetic contribution to the disorder. Recent genome-wide association studies (GWAS) of schizophrenia have been highly successful, identifying over 100 regions of the genome associated with risk. Despite this success, however, there remains uncertainty about the specific causal genes involved in schizophrenia, and how their function is regulated in development and disease. Sequencing the genome was, however, only the first step in our quest to understand how genes are expressed and regulated. Sitting above the DNA sequence is a second layer of information (the 'epigenome') that mediates the regulation of when and where genes are functionally transcribed. These mechanisms play a critical role in determining cell-type-specific patterns of gene transcription in the human brain.
This study aims, for the first time, to systematically examine the role of these regulatory genomic processes in schizophrenia. We will purify neuronal nuclei from a unique collection of post-mortem brain samples with the goal of identifying novel pathways involved in the disease. Given evidence for a neurodevelopmental component to schizophrenia, we will also annotate patterns of gene regulation across development of the human cortex, enabling us to explore the hypothesis that disease-associated loci are dynamically regulated during this critical period. Building on novel findings from our previous MRC-funded research, our integrated-genomics approach will bring together a world-class group of investigators and collaborators to explore the dynamic regulation of gene function during human brain development and its relevance to the aetiology of schizophrenia.
Studies into the causes of schizophrenia have focused on describing the genetic contribution to the disorder. Recent genome-wide association studies (GWAS) of schizophrenia have been highly successful, identifying over 100 regions of the genome associated with risk. Despite this success, however, there remains uncertainty about the specific causal genes involved in schizophrenia, and how their function is regulated in development and disease. Sequencing the genome was, however, only the first step in our quest to understand how genes are expressed and regulated. Sitting above the DNA sequence is a second layer of information (the 'epigenome') that mediates the regulation of when and where genes are functionally transcribed. These mechanisms play a critical role in determining cell-type-specific patterns of gene transcription in the human brain.
This study aims, for the first time, to systematically examine the role of these regulatory genomic processes in schizophrenia. We will purify neuronal nuclei from a unique collection of post-mortem brain samples with the goal of identifying novel pathways involved in the disease. Given evidence for a neurodevelopmental component to schizophrenia, we will also annotate patterns of gene regulation across development of the human cortex, enabling us to explore the hypothesis that disease-associated loci are dynamically regulated during this critical period. Building on novel findings from our previous MRC-funded research, our integrated-genomics approach will bring together a world-class group of investigators and collaborators to explore the dynamic regulation of gene function during human brain development and its relevance to the aetiology of schizophrenia.
Technical Summary
We propose the first comprehensive analysis of regulatory genomic variation associated with schizophrenia. Given evidence for a neurodevelopmental component to the aetiology of schizophrenia, we will also annotate patterns of gene regulation across development of the human cortex, enabling us to explore the hypothesis that disease-associated loci are dynamically regulated during this critical period.
We will first profile key markers of genomic regulation (DNA methylation (5mC), DNA hydroxymethylation (5hmC), and lysine H3K27 acetylation (H3K27ac)) in purified neuronal nuclei isolated from post-mortem prefrontal cortex tissue from >400 schizophrenia cases and matched controls.
We will next extend these analyses to human fetal cortex samples spanning ~7 to 20 weeks post-conception, enabling us to annotate functional genomic domains in the developing cortex and test the hypothesis that there is an enrichment of neurodevelopmentally-dynamic loci in regions of schizophrenia-associated regulatory genomic variation.
Alternative splicing and RNA isoforms dramatically increase the protein-coding potential of the human genome during development. Our third aim is to employ novel long-read sequencing approaches to undertake the first comprehensive analysis of RNA splicing and isoform diversity in both the developing and adult human cortex, exploring the role of alternative splicing in schizophrenia.
Finally, we will examine how schizophrenia-associated genetic variation influences regulatory genomic processes in the developing and adult cortex, building on our recent work showing that schizophrenia GWAS loci are enriched for 5mC quantitative trait loci in the developing brain.
Building on findings from our previous MRC-funded research, our integrated-genomics approach will enable us to explore the dynamic regulation of gene function during human brain development and its relevance to the aetiology of schizophrenia.
We will first profile key markers of genomic regulation (DNA methylation (5mC), DNA hydroxymethylation (5hmC), and lysine H3K27 acetylation (H3K27ac)) in purified neuronal nuclei isolated from post-mortem prefrontal cortex tissue from >400 schizophrenia cases and matched controls.
We will next extend these analyses to human fetal cortex samples spanning ~7 to 20 weeks post-conception, enabling us to annotate functional genomic domains in the developing cortex and test the hypothesis that there is an enrichment of neurodevelopmentally-dynamic loci in regions of schizophrenia-associated regulatory genomic variation.
Alternative splicing and RNA isoforms dramatically increase the protein-coding potential of the human genome during development. Our third aim is to employ novel long-read sequencing approaches to undertake the first comprehensive analysis of RNA splicing and isoform diversity in both the developing and adult human cortex, exploring the role of alternative splicing in schizophrenia.
Finally, we will examine how schizophrenia-associated genetic variation influences regulatory genomic processes in the developing and adult cortex, building on our recent work showing that schizophrenia GWAS loci are enriched for 5mC quantitative trait loci in the developing brain.
Building on findings from our previous MRC-funded research, our integrated-genomics approach will enable us to explore the dynamic regulation of gene function during human brain development and its relevance to the aetiology of schizophrenia.
Planned Impact
In addition to other scientists (especially other research groups investigating neurodevelopment and the aetiology of schizophrenia) the results of this project have the potential to impact on a number of other beneficiaries. These include patients suffering from schizophrenia, the pharmaceutical industry, health service providers, and academic groups investigating the causes of other complex disease phenotypes.
The social and economic consequences of schizophrenia are severe, eclipsing those of many other mental and somatic illnesses. With a lifetime prevalence rate of ~1%, the disorder contributes significantly to the global burden of disease, ranking among the top ten causes of disability in developed countries worldwide. Importantly, there is no cure for schizophrenia, and available treatments are often inefficient and characterised by severe side-effects. Given the dynamic and potentially-reversible nature of the epigenome, the outputs from this research could potentially nominate new targets for drug development for the treatment of schizophrenia. A number of pharmaceutical companies are actively developing so-called "epigenetic drugs" and could rapidly take advantage of these outputs. Our data may also highlight novel neurobiological pathways involved in schizophrenia, again stimulating the development of novel therapeutic interventions. Developing new treatments for schizophrenia will have subsequent benefits to the family and friends of affected individuals, and potentially boost the economy by enabling affected individuals to return to work. Of note, we work extensively with industrial partners and were recently funded by Eli Lilly's Lilly Research Award Program to undertake systems level genomic connectivity mapping in neural cell lines exposed to a panel of test compounds relevant to schizophrenia.
We propose to employ a range of cutting-edge technologies to undertake this work and develop novel strategies for performing integrated systems-level genomics analyses. This has the potential to not only benefit those scientists directly employed to work on the project, but may stimulate research into developmental genomics more broadly across the life sciences sector in the UK and beyond.
We are committed to communicating the impact of our research not only through standard scientific activities (high impact journals, conference attendance, and presentations at scientific seminars) but also via more accessible fora, such as our lab website (http://www.epigenomicslab.com/), Twitter (https://twitter.com/PsyEpigenetics) and the media (see http://www.epigenomicslab.com/media/ for media case-studies). Information arising from the proposed research will be communicated to the public following consultation with the host institutions and the MRC Press Office. Advice on dissemination of this research will also be sought from the host department, which has a strong track record in the public dissemination of scientific findings.
Finally, we hope that our novel integrated genetic-epigenetic approach to schizophrenia may stimulate similar research strategies to be adopted by academics working in the context of other complex disease phenotypes.
The social and economic consequences of schizophrenia are severe, eclipsing those of many other mental and somatic illnesses. With a lifetime prevalence rate of ~1%, the disorder contributes significantly to the global burden of disease, ranking among the top ten causes of disability in developed countries worldwide. Importantly, there is no cure for schizophrenia, and available treatments are often inefficient and characterised by severe side-effects. Given the dynamic and potentially-reversible nature of the epigenome, the outputs from this research could potentially nominate new targets for drug development for the treatment of schizophrenia. A number of pharmaceutical companies are actively developing so-called "epigenetic drugs" and could rapidly take advantage of these outputs. Our data may also highlight novel neurobiological pathways involved in schizophrenia, again stimulating the development of novel therapeutic interventions. Developing new treatments for schizophrenia will have subsequent benefits to the family and friends of affected individuals, and potentially boost the economy by enabling affected individuals to return to work. Of note, we work extensively with industrial partners and were recently funded by Eli Lilly's Lilly Research Award Program to undertake systems level genomic connectivity mapping in neural cell lines exposed to a panel of test compounds relevant to schizophrenia.
We propose to employ a range of cutting-edge technologies to undertake this work and develop novel strategies for performing integrated systems-level genomics analyses. This has the potential to not only benefit those scientists directly employed to work on the project, but may stimulate research into developmental genomics more broadly across the life sciences sector in the UK and beyond.
We are committed to communicating the impact of our research not only through standard scientific activities (high impact journals, conference attendance, and presentations at scientific seminars) but also via more accessible fora, such as our lab website (http://www.epigenomicslab.com/), Twitter (https://twitter.com/PsyEpigenetics) and the media (see http://www.epigenomicslab.com/media/ for media case-studies). Information arising from the proposed research will be communicated to the public following consultation with the host institutions and the MRC Press Office. Advice on dissemination of this research will also be sought from the host department, which has a strong track record in the public dissemination of scientific findings.
Finally, we hope that our novel integrated genetic-epigenetic approach to schizophrenia may stimulate similar research strategies to be adopted by academics working in the context of other complex disease phenotypes.
Organisations
- UNIVERSITY OF EXETER (Lead Research Organisation)
- UNIVERSITY OF EDINBURGH (Collaboration)
- Princeton University (Collaboration)
- Aarhus University (Collaboration)
- University College London (Collaboration)
- Eli Lilly & Company Ltd (Collaboration)
- Icahn School of Medicine at Mount Sinai (Collaboration)
- Cambridge Epigenetix (Collaboration)
- UK Biobank (Collaboration)
- UNIVERSITY OF CAMBRIDGE (Collaboration)
- UNIVERSITY OF ESSEX (Collaboration)
- University of Virginia Medical Center (Collaboration)
Publications
Alameda L
(2023)
Exploring the mediation of DNA methylation across the epigenome between childhood adversity and First Episode of Psychosis-findings from the EU-GEI study.
in Molecular psychiatry
Bell CG
(2019)
DNA methylation aging clocks: challenges and recommendations.
in Genome biology
Bell, Christopher G.
(2019)
DNA methylation aging clocks: challenges and recommendations
Caspi A
(2023)
Accelerated Pace of Aging in Schizophrenia: Five Case-Control Studies.
in Biological psychiatry
Chan RF
(2020)
Independent Methylome-Wide Association Studies of Schizophrenia Detect Consistent Case-Control Differences.
in Schizophrenia bulletin
El Khoury LY
(2019)
Systematic underestimation of the epigenetic clock and age acceleration in older subjects.
in Genome biology
Hannon E
(2019)
Genetic risk variants for brain disorders are enriched in cortical H3K27ac domains.
in Molecular brain
Description | AMP-CMD - Functional genomic annotations in human brain regions implicated in BMI and obesity |
Amount | £153,297 (GBP) |
Organisation | Foundation for the National Institutes of Health (FNIH) |
Sector | Charity/Non Profit |
Country | United States |
Start | 12/2022 |
End | 12/2024 |
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 | Brain & Behaviour Research Foundation - NARSAD Young Investigator Award - Anna Migdalska-Richards |
Amount | $70,000 (USD) |
Organisation | Brain & Behaviour Research Foundation |
Sector | Charity/Non Profit |
Country | United States |
Start | 01/2019 |
End | 12/2021 |
Description | Building on Brains for Dementia Research (BDR): A UK Nervous Tissue Network (UKNTN) for the Twenty-first Century |
Amount | £1,855,571 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2022 |
End | 10/2025 |
Description | Defining Best Practises for Data Science Education across Disciplines |
Amount | £16,191 (GBP) |
Organisation | Alan Turing Institute |
Sector | Academic/University |
Country | United Kingdom |
Start | 01/2023 |
End | 01/2024 |
Description | Developing a blood test for the early detection of ALS |
Amount | $100,000 (USD) |
Organisation | The ALS Association |
Sector | Charity/Non Profit |
Country | United States |
Start | 12/2022 |
End | 01/2025 |
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 | Exeter Brain Network |
Amount | £10,000 (GBP) |
Organisation | University of Exeter |
Sector | Academic/University |
Country | United Kingdom |
Start | 01/2023 |
End | 01/2024 |
Description | Exploring the role of epigenetic mechanisms in the manifestation of Huntington's disease |
Amount | £1,248,387 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2024 |
End | 03/2027 |
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 | The Autism Prenatal Sex Differences (APEX) study |
Amount | $16,000,000 (USD) |
Organisation | Simons Foundation |
Sector | Charity/Non Profit |
Country | United States |
Start | 01/2022 |
End | 01/2027 |
Title | Barcoded and targeted cDNA library preparation for Oxford Nanopore Technologies sequencing |
Description | The NEBNext Single Cell/Low Input cDNA Synthesis & Amplification Module (NEB) was adapted for the purpose of adding Oxford Nanopore Technologies (ONT) compatible barcodes during reverse transcription of RNA. This is a useful process for multiplexing low input samples for ONT transcriptome library preparation. An optional step before ONT library preparation is the targeted enrichment of cDNA molecules using IDT hybridisation probes. Here we provide a protocol for this process based on the 'PacBio cDNA capture using IDT xGen Lockdown Probes' protocol. Using this approach, up to 100 samples can be barcoded with individual ONT barcodes via reverse transcription. Samples can then be pooled together and a cDNA PCR amplification performed. This allows sufficient material for cDNA enrichment and/or ONT ligation sequencing library preparation. |
Type Of Material | Technology assay or reagent |
Year Produced | 2024 |
Provided To Others? | Yes |
Impact | Requests for more information on our protocol. |
URL | https://www.protocols.io/view/barcoded-and-targeted-cdna-library-preparation-for-kqdg3xzwzg25/v1 |
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 | Purification of human cortex excitatory neuron nuclei from fetal and postnatal tissue using fluorescent activated nuclei sorting (FANS) in combination with a SATB2 antibody. |
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. This protocol builds on a previous protocol that uses fluorescence-activated nuclei sorting (FANS) to isolate and profile nuclei from multiple different human brain cell-types from frozen post-mortem tissue. Because NeuN is not an optimal marker for neuronal nuclei from fetal cortex, we have optimized a method using a SATB2 antibody to purify nuclei from excitatory neurons in both fetal and postnatal cortex. Purified populations of nuclei are amenable to simultaneous profiling of i) DNA modifications (via bisulfite sequencing / array), ii) histone modifications (via CUT&Tag), iii) open chromatin analysis (via ATAC-seq), and iv) gene expression (via RNA-seq). |
Type Of Material | Technology assay or reagent |
Year Produced | 2023 |
Provided To Others? | Yes |
Impact | This protocol has been used by several other groups and in our own work on the developing human brain. |
URL | https://www.protocols.io/view/purification-of-human-cortex-excitatory-neuron-nuc-b4efqtbn.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 |
Title | Long-read transcriptome data (Iso-Seq) of the human and mouse brain |
Description | Datasets from "Full-length transcript sequencing of human and mouse cerebral cortex identifies widespread isoform diversity and alternative splicing", SK.Leung, A.Jeffries. et al. (2021) Deposited files are generated from running Cupcake, SQANTI2 (v7.4) and filter. Note, only the files generated from SQANTI2 filtering are deposited. To re-run SQANTI, use the files in cupcake_collapse folder as input. Please refer to code (https://github.com/SziKayLeung/Whole_Transcriptome_Paper) for more information. Datasets: - AdultCTX: Adult human prefrontal cortex tissue (n = 4) merged dataset - FetalCTX: Fetal human prefrontal cortex tissue (n = 3) merged dataset - FetalHIP: Fetal human hippocampus tissue (n = 2, subset of FetalCTX) merged dataset - FetalSTR: Fetal human striatum tissue (n = 2, subset of FetalCTX) merged dataset - MouseCTX: Mouse entorhinal cortex tissue (n = 12) merged dataset |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
URL | https://zenodo.org/record/7611813 |
Title | Uncertainty quantification of reference-based cellular deconvolution algorithms |
Description | The majority of epigenetic epidemiology studies to date have generated genome-wide profiles from bulk tissues (e.g., whole blood) however these are vulnerable to confounding from variation in cellular composition. Proxies for cellular composition can be mathematically derived from the bulk tissue profiles using a deconvolution algorithm; however, there is no method to assess the validity of these estimates for a dataset where the true cellular proportions are unknown. In this study, we describe, validate and characterize a sample level accuracy metric for derived cellular heterogeneity variables. The CETYGO score captures the deviation between a sample's DNA methylation profile and its expected profile given the estimated cellular proportions and cell type reference profiles. We demonstrate that the CETYGO score consistently distinguishes inaccurate and incomplete deconvolutions when applied to reconstructed whole blood profiles. By applying our novel metric to >6,300 empirical whole blood profiles, we find that estimating accurate cellular composition is influenced by both technical and biological variation. In particular, we show that when using a common reference panel for whole blood, less accurate estimates are generated for females, neonates, older individuals and smokers. Our results highlight the utility of a metric to assess the accuracy of cellular deconvolution, and describe how it can enhance studies of DNA methylation that are reliant on statistical proxies for cellular heterogeneity. To facilitate incorporating our methodology into existing pipelines, we have made it freely available as an R package (https://github.com/ds420/CETYGO). |
Type Of Material | Database/Collection of data |
Year Produced | 2023 |
Provided To Others? | Yes |
URL | https://tandf.figshare.com/articles/dataset/Uncertainty_quantification_of_reference-based_cellular_d... |
Title | Uncertainty quantification of reference-based cellular deconvolution algorithms |
Description | The majority of epigenetic epidemiology studies to date have generated genome-wide profiles from bulk tissues (e.g., whole blood) however these are vulnerable to confounding from variation in cellular composition. Proxies for cellular composition can be mathematically derived from the bulk tissue profiles using a deconvolution algorithm; however, there is no method to assess the validity of these estimates for a dataset where the true cellular proportions are unknown. In this study, we describe, validate and characterize a sample level accuracy metric for derived cellular heterogeneity variables. The CETYGO score captures the deviation between a sample's DNA methylation profile and its expected profile given the estimated cellular proportions and cell type reference profiles. We demonstrate that the CETYGO score consistently distinguishes inaccurate and incomplete deconvolutions when applied to reconstructed whole blood profiles. By applying our novel metric to >6,300 empirical whole blood profiles, we find that estimating accurate cellular composition is influenced by both technical and biological variation. In particular, we show that when using a common reference panel for whole blood, less accurate estimates are generated for females, neonates, older individuals and smokers. Our results highlight the utility of a metric to assess the accuracy of cellular deconvolution, and describe how it can enhance studies of DNA methylation that are reliant on statistical proxies for cellular heterogeneity. To facilitate incorporating our methodology into existing pipelines, we have made it freely available as an R package (https://github.com/ds420/CETYGO). |
Type Of Material | Database/Collection of data |
Year Produced | 2023 |
Provided To Others? | Yes |
URL | https://tandf.figshare.com/articles/dataset/Uncertainty_quantification_of_reference-based_cellular_d... |
Title | mQTL and SMR database |
Description | As part of our project identifying DNA methylation quantitative trait loci and using these to fine-map genetic association signals we have created an online database/tool that enables other research groups to use these data in their work. |
Type Of Material | Database/Collection of data |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | We have several groups contact us for collaboration. The data has been used in several other studies. |
URL | https://epigenetics.essex.ac.uk/shiny/ShinySMR/ |
Description | Collaboration with Cambridge Epigenetix |
Organisation | Cambridge Epigenetix |
Country | United Kingdom |
Sector | Private |
PI Contribution | Our lab is beta testing a new chemistry for profiling DNA methylation and DNA hydroxymethylation. |
Collaborator Contribution | We were provided with early access to a new kit, free of charge. |
Impact | Experiments ongoing. |
Start Year | 2023 |
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 John Hardy and group, UCL |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We are working with John Hardy and his team on a collaboration to use long-read sequencing to map isoform diversity in Alzheimer's disease. |
Collaborator Contribution | We are sharing protocols, analysis pipelines and data. |
Impact | We aim to submit a new research grant in the next year. |
Start Year | 2023 |
Description | Collaboration with Olga Troyanskaya and team |
Organisation | Princeton University |
Country | United States |
Sector | Academic/University |
PI Contribution | We have established a collaboration with Olga Troyanskaya and her team. We are providing data and bioinformatics pipelines to the collaboration. |
Collaborator Contribution | They are using our data to generate deep-learning models for the prediction of cell-specific epigenetic states and alternative splicing of transcripts. |
Impact | The collaboration has just started but we are planning to develop models for predicting transcriptional states and epigenetic regulation using AI. |
Start Year | 2023 |
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 | Epigenetics in UK Biobank |
Organisation | UK Biobank |
Country | United Kingdom |
Sector | Charity/Non Profit |
PI Contribution | We are leading a consortium effort to raise funds to generate DNA methylation data in the UK Biobank cohort |
Collaborator Contribution | UK Biobank have provided networking opportunities with potential funders (commercial and non-commercial) |
Impact | I presented at the UK Bioabank annual conference in London and will be speaking at a fund-raising event in California in March 2024. |
Start Year | 2023 |
Description | Functional Genomics workgroup in the Psychiatric Genomics Consortium |
Organisation | University of Cambridge |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We are leading a sub-group on alternative splicing and epigenetics. This will establish an international collaborative research program. |
Collaborator Contribution | Providing data and analysis plans. |
Impact | We have established a new functional genomics working group within the PGC. I am on the management committee and leading a sub-group on alternative splicing. |
Start Year | 2023 |
Description | Functional Genomics workgroup in the Psychiatric Genomics Consortium |
Organisation | University of Edinburgh |
Department | Edinburgh Genomics |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We are leading a sub-group on alternative splicing and epigenetics. This will establish an international collaborative research program. |
Collaborator Contribution | Providing data and analysis plans. |
Impact | We have established a new functional genomics working group within the PGC. I am on the management committee and leading a sub-group on alternative splicing. |
Start Year | 2023 |
Description | - London Calling, Oxford Nanopore Technologies Conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | Invited platform presentation at flagship ONT meeting in London. Title - Long read transcriptome sequencing reveals isoform diversity across human neurodevelopment and aging. |
Year(s) Of Engagement Activity | 2022 |
URL | https://londoncallingconf.co.uk/lc23 |
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 Awareness Week, Public Engagement Seminar: 13th - 19th March 2019 Title: Schizophrenia: Examining the light switches of our DNA |
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 Brain Awareness Week activities in Exeter, we presented an overview of our ongoing work into the genomics of schizophrenia. This even was targeted at a lay audience and stimulated considerable interest. |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.brainawareness.org/ |
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 | 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 | College student visit |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | We hosted a college student thinking about applying for medicine at the RILD building. I demonstrated examples of medical research and organised a tour/chats with RILD colleagues. |
Year(s) Of Engagement Activity | 2024 |
Description | Developmental trajectories of DNA methylation in the human cortex: evidence for sex differences - Poster presentation at the Epigenomics of Common Diseases conference (Wellcome Connecting Science, Hinxton, UK |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Presentation on our work into sex differences in the human brain. Led to new collaboration opportunities. |
Year(s) Of Engagement Activity | 2023 |
Description | Disrupted microRNA expression in the dorsolateral prefrontal cortex is associated with schizophrenia - Poster 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 work on microRNA changes in the brain of schizophrenia patients. The data was well-recieeved and we are now writing a paper for publication based on these results. |
Year(s) Of Engagement Activity | 2019 |
URL | https://coursesandconferences.wellcomegenomecampus.org/register/conferences/form1.aspx?e=771 |
Description | Epigenetics Workshop at NIMHANS, Bangalore |
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 | We organised a training workshop at the National Institute of neuroscience and mental Health in Bangalore. We provided training to local researchers and psychiatrists into genetics, genomics and epigenetics. Were hope to work with teams in India to instigate a program of cross-national psychiatric epigenetics research. |
Year(s) Of Engagement Activity | 2019 |
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 | 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 | 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 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 Sheffield Institute of Translational Neuroscience |
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 at SITRAN where I presented our work on genomic profiling in human neurodegenerative disease. The talk led to several new collaboration opportunities. |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.sheffield.ac.uk/sitran |
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 | 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 | Mapping cell-type specific markers of genomic variation in purified nuclei populations isolated from the human cortex - presentation at the Wellcome Trusy 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 experimental pipeline that uses fluorescence-activated nuclei sorting (FANS) to isolate and profile nuclei from different neural cell-types. We demonstrated that this can be used to robustly purify neuron-, oligodendrocyte- and gliaenrichedpopulations of nuclei from adult and fetal frozen cortex tissue, with each tissue sample yielding purified populations of nuclei amenable to simultaneous analysis of i) DNA modification analysis (5mC and 5hmC), ii) histone modification (ChIP-seq), iii) open chromatin (ATAC-seq), and iv) gene expression (RNA-seq). There was considerable interest in our method and requests 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 | Neurogenomics Seminar - Imperial College London |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Members of the team were invited to present our work at the online [international reach] Imperial College London neuogenomics seminar. Several hundred attendees joined the meeting and many questions were asked. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.youtube.com/watch?v=32_R9P_T0sQ |
Description | New Horizon's in Genomics - Queen Mary's University London |
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 our work on leveraging Quantitative-Trait Loci to Characterize the Relationship between Methylomic Variation, Gene Expression, and Complex Traits. We provided a discussion of the methods used in our MRC-funded study of schizophrenia. |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.evensi.uk/qmul-horizons-genomics-genome-sequencing-analysis-garrod-building-barts-london... |
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 | 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 at UK Biobank annual conference |
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 a presentation on the promise of profiling DNA methylation in UK biobank. As a result of this we have established an academic consortium to pursue funding to achieve this goal. |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&cad=rja&uact=8&ved=2ahUKEwj_rMDC8-uEA... |
Description | Presentation 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 | I gave a presentation about our work on alternative splicing in the developing brain and schizophrenia at the WCPG meeting in Montreal, Canada in October 2023. I had several requests for more information and collaboration. |
Year(s) Of Engagement Activity | 2023 |
URL | https://ispg.net/events/wcpg-2023-invitation-to-attend/ |
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 | Presentations at the World Congress of Psychiatric Genetics, Florence, Italy. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | We gave multiple presentations at the 2022 WCPG meeting in Florence, showcasing the results of our research projects. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.emedevents.com/c/medical-conferences-2022/world-congress-of-psychiatric-genetics-wcpg-20... |
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 | Talk at the Festival of Genomics |
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 a presentation on the use of long-read RNA sequencing for characterising transcript variation in the human brain. |
Year(s) Of Engagement Activity | 2024 |
URL | https://festivalofgenomics.com/london/en/page/home |
Description | Tools for the next generation of EWAS - presentation 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 a suite of innovative and data-driven tools focussed on quality controlling DNA methylation microarray data. These tools are designed to test for common problems such as inefficient bisulfite conversion, sample outliers, probe outliers, gradients within individual slides and variation introduced through (possibly unsuitable) normalisation (normalisation violence). The resource was of general interest to the audience and sparked considerable discussion. |
Year(s) Of Engagement Activity | 2019 |
URL | https://coursesandconferences.wellcomegenomecampus.org/register/conferences/form1.aspx?e=771 |
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 |