COMPUTATIONAL GENOMICS ANALYSIS AND TRAINING (CGAT)AT THE MRC FUNCTIONAL GENOMICS UNIT
Lead Research Organisation:
University of Oxford
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Organisations
- University of Oxford (Lead Research Organisation)
- Francis Crick Institute (Collaboration)
- University College London (Collaboration)
- University of Basel (Collaboration)
- UNIVERSITY OF STRATHCLYDE (Collaboration)
- IMPERIAL COLLEGE LONDON (Collaboration)
- UNIVERSITY OF EXETER (Collaboration)
- UNIVERSITY OF OXFORD (Collaboration)
- University of Sheffield (Collaboration)
- Cardiff University (Collaboration)
- University of Bath (Collaboration)
- UNIVERSITY OF EDINBURGH (Collaboration)
- Medical Research Council (MRC) (Collaboration)
- University of Bristol (Collaboration)
- KING'S COLLEGE LONDON (Collaboration)
People |
ORCID iD |
Publications
Rajan P
(2014)
Next-generation sequencing of advanced prostate cancer treated with androgen-deprivation therapy.
in European urology
Sims D
(2014)
Sequencing depth and coverage: key considerations in genomic analyses.
in Nature reviews. Genetics
Cooper S
(2014)
Targeting polycomb to pericentric heterochromatin in embryonic stem cells reveals a role for H2AK119u1 in PRC2 recruitment.
in Cell reports
Vance KW
(2014)
The long non-coding RNA Paupar regulates the expression of both local and distal genes.
in The EMBO journal
Chalei V
(2014)
The long non-coding RNA Dali is an epigenetic regulator of neural differentiation.
in eLife
Sims D
(2014)
CGAT: computational genomics analysis toolkit.
in Bioinformatics (Oxford, England)
Saliba DG
(2014)
IRF5:RelA interaction targets inflammatory genes in macrophages.
in Cell reports
Pfeffer G
(2015)
SPG7 mutations are a common cause of undiagnosed ataxia.
in Neurology
| Description | MRC Molecular Cellular Medicine Board - supplementary funding (CGAT) |
| Amount | £614,100 (GBP) |
| Funding ID | MC_EX_G1000902 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 07/2015 |
| End | 03/2016 |
| Title | CGAT Code Collection |
| Description | A manuscript was published in Bioinformatics presenting how to get started with the CGAT Code Collection: http://bioinformatics.oxfordjournals.org/content/30/9/1290 |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2014 |
| Provided To Others? | Yes |
| Impact | Unknown -- provided to bioinformatics community at large |
| URL | http://bioinformatics.oxfordjournals.org/content/30/9/1290 |
| Title | Computational genomics pipelines |
| Description | Software for the analysis of next generation sequencing data. |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2010 |
| Provided To Others? | Yes |
| Impact | CGAT members contribute to the development of open source software provided to bioinformatics community at large for the analysis of Next Generation Sequencing data. The code is publicly available from GitHub: https://github.com/CGATOxford |
| URL | https://github.com/CGATOxford |
| Title | Software Sustainability |
| Description | CGAT has been successfully evaluated by the Software Sustainability Institute which confirmed that CGAT's software development process follow best practices (report available): http://www.software.ac.uk/blog/2015-02-05-introduction-cgat |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2015 |
| Provided To Others? | Yes |
| Impact | Unknown |
| URL | http://www.software.ac.uk/blog/2015-02-05-introduction-cgat |
| Title | UMI-tools |
| Description | Tools for handling Unique Molecular Identifiers in NGS data sets |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2017 |
| Provided To Others? | Yes |
| Impact | A manuscript was published in Genome Research: UMI-tools: modeling sequencing errors in Unique Molecular Identifiers to improve quantification accuracy |
| URL | https://github.com/CGATOxford/UMI-tools |
| Description | Proj 001 (Lindsay) |
| Organisation | University of Bath |
| Department | Department of Pharmacy and Pharmacology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Analysis of microarray and Chip-Seq data. Research question focuses on: lincRNAs in human macrophages. |
| Collaborator Contribution | Expertise in the role of non-coding RNAs in the innate immune response; provision of above data for analysis |
| Impact | Paper: Long non-coding RNAs and enhancer RNAs regulate the lipopolysaccharide-induced inflammatory response in human monocytes. IIott NE, Heward JA, Roux B, Tsitsiou E, Fenwick PS, Lenzi L, Goodhead I, Hertz-Fowler C, Heger A, Hall N, Donnelly LE, Sims D, Lindsay MA. Nat Commun. 2014 Jun 9. |
| Start Year | 2011 |
| Description | Proj 008 (Udalova) |
| Organisation | Imperial College London |
| Department | Faculty of Medicine |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We are conducting integrative meta-analysis of different types of data (gene expression data, ChIP-Seq, RNA-Seq). Research question focuses on: co-regulation of macrophage inflammatory phenotype by IRF5 and RelA. |
| Collaborator Contribution | Knowledge of IRF transcription factors in establishing phenotype of immune cells; provision of above data for analysis |
| Impact | Paper: IRF5:RelA Interaction Targets Inflammatory Genes in Macrophages. Saliba DG, Heger A, Eames HL, Oikonomopoulos S, Teixeira A, Blazek K, Androulidaki A, Wong D, Goh FG, Weiss M, Byrne A, Pasparakis M, Ragoussis J, Udalova IA. Cell Rep. 2014 Sep 11. |
| Start Year | 2011 |
| Description | Proj 010 (Tybulewicz) |
| Organisation | Medical Research Council (MRC) |
| Department | MRC National Institute for Medical Research (NIMR) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Design and analysis of RNAseq experiments; mining of existing data relating to lincRNAs, CHIPseq data on B cell transcription factors; interpretation of data leading to design of follow up studies. Research question focuses on: the role that lincRNAs play in the development and activation of B cells. |
| Collaborator Contribution | Extensive experience in the analysis of how mutations perturb B cell development and activation; provision of above data for analysis; experience of performing RNAseq experiments. |
| Impact | Paper: Brazao, T.*, Johnson, J.*, Ponting, C., Heger, A., Tybulewicz, V. "Long non-coding RNAs expressed in naïve and activated B cells" |
| Start Year | 2012 |
| Description | Proj 011 (Hammond) |
| Organisation | University of Bristol |
| Department | School of Physiology, Pharmacology and Neuroscience |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Advising on collection of appropriate sequence data; analysing the data collected. Research question focuses on: mapping genes that cause osteoarthritis in zebrafish using NGS |
| Collaborator Contribution | Unique knowledge of the zebrafish model in studying the genetics of osteoarthritis. |
| Impact | On going awaiting collaborator validation. |
| Start Year | 2012 |
| Description | Proj 013 (Drake) |
| Organisation | University of Edinburgh |
| Department | Centre for Cardiovascular Science |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Storage, processing and interpretation of large amounts of data from enrichment of 5mC. |
| Collaborator Contribution | Project title: The role of DNA methylation and hydroxymethylation in the programming of neurodevelopment Contributions from collaborators include: dissected brain tissue available from their well-characterised rat model of prenatal glucocorticoid overexposure; enrichment of 5mC and 5hmC performed using affinity based methods. |
| Impact | No findings |
| Start Year | 2013 |
| Description | Proj 014 (Karadimitris) |
| Organisation | Imperial College London |
| Department | Centre for Haematology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Computational and statistical analysis and visual representation of the data resulting from sequencing of eighteen e4C-Seq and ChiP-e4C-Seq libraries. Research question focuses on: the impact of a disease-causing mutation on the genomic interactome. |
| Collaborator Contribution | Expertise in the epigenetic basis of disease; extensive experience with ChiP assays, chromosome conformation capture-based techniques such as 3C and enhanced 4C-Seq (e4C-seq), lentiviral overexpression and knock down systems, advanced flow-cytometry and sorting, protein biochemistry, cell culture and xenograft models of multiple myeloma. |
| Impact | Awaiting new data |
| Start Year | 2012 |
| Description | Proj 015 (Minczuk) |
| Organisation | Medical Research Council (MRC) |
| Department | MRC Mitochondrial Biology Unit |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Overall: The analysis of raw sequencing data that involves mapping and alignment of mt-RNA-derived reads. Specifically: designing the deep RNASeq approach allowing for precise analysis of mt-RNA; performing the next generation sequencing; analysis and interpretation of large volumes of sequence data |
| Collaborator Contribution | Project title: RNA polyadenylation and the maintenance and expression of the mitochondrial genome Establishing how poly(A) tails regulate mt-RNA abundance and mitochondrial protein synthesis. Identifying novel proteins that play a role in mitochondrial poly(A) tail metabolism. Determining whether poly(U) extensions play a role in RNA surveillance and/or turnover in human mitochondria. Elucidating the mechanism of mtDNA replication via sequencing of the RNAs associated with mitochondrial replication intermediates. |
| Impact | no outcome |
| Start Year | 2013 |
| Description | Proj 016 (Houlden) |
| Organisation | University College London |
| Department | Institute of Neurology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Analysis of exome data -- focusing on channel genes and determining if channel variants are causing episodic ataxia. Specifically: Exome analysis in families, in one or more affected individuals and in unaffected cases. Exome analysis of sporadic individuals for de-novo mutations. Investigating if variants in more than one channel gene can cause sporadic episodic ataxia or if these variants modify the clinical picture, age at onset and severity. |
| Collaborator Contribution | Project title: Collaborative project on next generation sequencing in brain channelopathies Episodic ataxia is an inherited disorder characterized by the core features of ataxia, migraine headaches, vertigo and seizures. The main genes known to cause this disorder are CACNA1A and KCNA1. Our partners have identified a number of small kindreds which have at least one affected member with episodic ataxia that are negative for the known channel genes, CACNA1A and KCNA1. They also have a number of sporadic cases with typical early onset episodic ataxia, again these are negative for the known genes and they have examined and imaged the parents. Our partners wish to perform next generation exome sequencing to identify the disease gene(s). |
| Impact | Currently writing manuscript. |
| Start Year | 2013 |
| Description | Proj 018 (Bundy) |
| Organisation | Imperial College London |
| Department | Faculty of Medicine |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Data analysis including assembly, annotation, identification of SNPs and indels, and mapping them to genomic features and classification into genic/intergenic and synonymous/non-synonymous. Also exploring ways to mine datasets. |
| Collaborator Contribution | Project title: Understanding adaptation of Pseudomonas aeruginosa to the cystic fibrosis lung environment Our partners have contributed 96 clinical isolates taken from clonal P. aeruginosa infections of individual CF patients over many years. They have extracted Genomic DNA and performed QCs. |
| Impact | Results will be published, but we are currently at the analysis stage. |
| Start Year | 2013 |
| Description | Proj 019 (Mill) |
| Organisation | King's College London |
| Department | Institute of Psychiatry, Psychology & Neuroscience |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Analysis of bisulfite sequencing data |
| Collaborator Contribution | Project title: Mapping cell-type specific methylomes in the human brain: reduced representation bisulfite sequencing (RRBS) in neurons, microglia and astrocytes Our partners have contributed laser-capture microdissection (LCM) methods to specifically isolate the three major cell types of the brain (microglia, astrocytes and neurons) from post-mortem cortical tissue. |
| Impact | Data generated unsuccessful |
| Start Year | 2013 |
| Description | Proj 020 (Pickard) |
| Organisation | University of Strathclyde |
| Department | Strathclyde Institute of Pharmacy & Biomedical Sciences |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Aiding in experimental design; data analysis with regards to normalization and statistical significance of adjusted fusion transcript abundances; discussion of biological interpretation of data. Research question focuses on: a cell-based gene trap to reveal the mechanisms of lithium, a treatment for bipolar disorder. |
| Collaborator Contribution | Expertise in the genetics and biology underlying risk of psychiatric disorders; provision of data for analysis |
| Impact | Project is at the experimental validation stage. |
| Start Year | 2012 |
| Description | Proj 022 (Brockdorff) |
| Organisation | University of Oxford |
| Department | Department of Biochemistry |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Analysis of H3K27me3 ChIP in Dnmt mutant cells. Analysis of ES cells grown in 2i conditions. Correlation of whole genome bisulfite data and H3K27me3 chip-seq data. |
| Collaborator Contribution | Project title: Polycomb recruitment and DNA methylation PcG ChIP-seq experiments using transcriptional inhibitors and/or knockdown of factors required for establishment of H3K4me3 and H3K36me3 both in wild-type and DNA methylation depleted ES cells. The aim is to assess the role of transcription linked histone modifications in defining PcG redistribution patterns in the presence and absence of DNA methylation. |
| Impact | Paper: Targeting Polycomb to Pericentric Heterochromatin in Embryonic Stem Cells Reveals a Role for H2AK119u1 in PRC2 Recruitment. Cooper S, Dienstbier M, Hassan R, Schermelleh L, Sharif J, Blackledge NP, De Marco V, Elderkin S, Koseki H, Klose R, Heger A, Brockdorff N. Cell Rep. 2014 May 21. |
| Start Year | 2013 |
| Description | Proj 023 (Rehwinkel) |
| Organisation | University of Oxford |
| Department | Weatherall Institute of Molecular Medicine (WIMM) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Bioinformatic analysis of retroelement sequences. |
| Collaborator Contribution | Project title: Retroelements and Aicardi-Goutières syndrome Generation of Samhd1 null mice. Preliminary data showing that IFN is spontaneously produced in Samhd1 -/- mouse embryonic fibroblasts (MEFs), macrophages, and in spleen tissue. Provision of Trex1 null mice as well as human cells from AGS patients harbouring mutations within these genes. |
| Impact | Data generated unsuccessful |
| Start Year | 2013 |
| Description | Proj 024 (Fry & Pilz) |
| Organisation | Cardiff University |
| Department | School of Medicine |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Analysis of exome data to include: Integration of different data sources: CNVs, exome data from trios (focused on DNMs) and small families (looking at rare inherited variation). Detection of mosaicism. Pathway analysis. Comparison with other brain phenotypes. |
| Collaborator Contribution | Project title: What is the genetic basis of polymicrogyria? Our partners have contributed: Genomic DNA from whole blood (and/or saliva). Extensive phenotype data. cMRI brain scans. NHS gene tests and screening by SNP-array or array-CGH for copy number variants (CNVs). |
| Impact | Manuscript submitted |
| Start Year | 2013 |
| Description | Proj 025 (Chapman) |
| Organisation | University of Edinburgh |
| Department | Centre for Cardiovascular Science |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Library preparation, sequencing and computational/bioinformatic analysis of nucleic acid from gut contents |
| Collaborator Contribution | Project title: GLUCOCORTICOIDS AND GUT IMMUNITY: DOES DEFICIENCY IN 11 -HSD1 ALTER THE GUT MICROBIOME? Contributions from partners: gut microbiome of 11 -HSD1-deficient and control C57BL/6J mice fed standard chow or western diet (0.21% cholesterol, 39% fat; Research Diets, D12079B) for 2 weeks (4 groups, n=6/group). The aim is to establish whether the gut microbiota of 11?-HSD1-deficient mice differs from that of controls. Combined caecal and faecal contents will be collected from mice (24 in total) and DNA extracted using a QIAamp DNA stool mini kit (Qiagen). |
| Impact | Manuscript submitted |
| Start Year | 2013 |
| Description | Proj 026 (Hemsley) |
| Organisation | University of Exeter |
| Department | College of Life and Environmental Sciences |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Analysis of gene expression data. Pathway analyses. Motif analysis. |
| Collaborator Contribution | Project title: The glycine riboswitch in Burkholderia pseudomallei and its role in virulence Provision of four different conditions, each with two biological replicates, for analysis: A) B. pseudomallei strain K96243 wild type grown in absence of glycine; B) K96243 wild type grown in presence of glycine; C) K96342 ?gcvP (hypervirulent mutant) grown in absence of glycine, and D) K96342 ?gcvP grown in presence of glycine. |
| Impact | Awaiting data validation |
| Start Year | 2013 |
| Description | Proj 027 (Pennings) |
| Organisation | University of Edinburgh |
| Department | Centre for Cardiovascular Science |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Interrogation of NGS mapping datasets in a linear way for micro patterns as well as in a more contextual mode for mega pattern analysis of large chromosomal regions. |
| Collaborator Contribution | Project title: Epigenomic analysis of gene silencing in cardiac development and reprogramming |
| Impact | Awaiting validation |
| Start Year | 2013 |
| Description | Proj 028 (Wilson) |
| Organisation | University of Sheffield |
| Department | Department of Molecular Biology and Biotechnology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Define the mRNA and non-coding RNA sequences bound by Nxf1, Chtop and Alyref. Examine those sequences for a) consensus motifs b) proximity to exonic splice enhancer sequences recognised by SR proteins and possibly other mRNP binding proteins c) RNA secondary structures. |
| Collaborator Contribution | Project title: RNA export factors and their association with coding and non-coding RNAs Our partners will provide RIP (RNA immunoprecipitation) - CHIP datasets for several mRNA export factors using the agilent mRA array platform; and total and cytoplasmic RNA transcriptome data generated using the agilent human mRNa array platform for cells where individual TREX subunits have been depleted. |
| Impact | Manuscript in preparation |
| Start Year | 2013 |
| Description | Proj 031 (Vance) |
| Organisation | University of Oxford |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Data analysis |
| Collaborator Contribution | Data |
| Impact | Paper: The long non-coding RNA Paupar regulates the expression of both local and distal genes. Vance KW, Sansom SN, Lee S, Chalei V, Kong L, Cooper SE, Oliver PL, Ponting CP. EMBO J. 2014 Feb 18 |
| Start Year | 2013 |
| Description | Proj 033 (Nemeth) |
| Organisation | University of Oxford |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Provision of novel analytical approaches to identify candidate causative variants in early-onset ataxia pedigrees of differing structure. |
| Collaborator Contribution | Project title: Early-onset ataxia whole exome sequencing Research question: The aim of this study is to identify mutations in novel genes in children with unexplained ataxia and better characterise the relationship between the clinical features and the genotype, including whether the condition is likely to progress or not. A key component of this will be to use functional models of candidate causative variants to dissect out the biological pathways important to childhood ataxia. |
| Impact | 10.1212/WNL.0000000000001369 10.1093/brain/awv117 10.1002/mdc3.12372 |
| Start Year | 2014 |
| Description | Proj 034 (Drake) |
| Organisation | University of Edinburgh |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Data storage and processing capacity. |
| Collaborator Contribution | Project title: Mechanisms underlying the transmission of programming effects Research question: Can we identify a mechanism for the transmission of programmed effects to a second generation? |
| Impact | Manuscript submitted |
| Start Year | 2014 |
| Description | Proj 035 (Drake) |
| Organisation | University of Edinburgh |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Processing, analysis and interpretation of the data and further hypothesis generation. |
| Collaborator Contribution | Project title: Does exposure to a high fat diet lead to effects on the germline epigenome? Hypothesis: A high fat diet disrupts the germ line epigenome resulting in perturbed reproductive and metabolic health in subsequent generations. |
| Impact | 10.1038/srep31857 |
| Start Year | 2014 |
| Description | Proj 036 (Tybulewicz) |
| Organisation | Francis Crick Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Design and analysis of RNA-seq experiments; mining of existing data relating to lincRNAs, ChIP-seq data on B cell transcription factors; correlation of gene expression; interpretation of data leading to design of follow up studies. |
| Collaborator Contribution | Design and implementation of RNAseq timecourse experiments to identify lncRNAs with important functions in B cells. Validation of roles of cancidate lncRNAs from computational analysis. |
| Impact | Manuscript in preparation for peer review. |
| Start Year | 2014 |
| Description | Proj 038 (Ryan) |
| Organisation | University of Oxford |
| Department | Department of Oncology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Calling somatic variants by careful comparison with matched normal (non-tumor) tissue from the same patient. Fintering and annotation of variants using a wide range of criteria and data sources. Integration of data from short hairpin RNAi screen. |
| Collaborator Contribution | Exome sequencing of both tumour and non-tumour tissue from Non-Smoking Related Lung Cancer (NSRLC) to identify novel driver mutations. |
| Impact | Candidate driver mutation for laboratory validation by collaborators. |
| Start Year | 2014 |
| Description | Proj 040 (D'Angiolella) |
| Organisation | University of Oxford |
| Department | Department of Oncology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Mapping next generation sequencing reads to the shRNA library and performing statistical analyses to identity genes with differential effects on cell viability across the two cell lines. Integration of gene expression data from the screening cell line. Annotation of screen hits with chemical compounds. |
| Collaborator Contribution | Screening genome-wide shRNA libraries in isogenic cell lines to identify the genes that are synthethic lethal with MTAP. Validation of screen hits using orthoganol methods. |
| Impact | Awaiting validation |
| Start Year | 2014 |
| Description | Proj 043 (Knight) |
| Organisation | University of Oxford |
| Department | Wellcome Trust Centre for Human Genetics |
| Country | United Kingdom |
| Sector | Charity/Non Profit |
| PI Contribution | Analysis of genetic variation, genome-wide gene expression and integration with other data (biochemical and phenotypic) in the context of a clinical trial. Identification of eQTL associated with vitamin D supplementation. |
| Collaborator Contribution | Our collaborators have performed a clinical trial to assess the optimal dose of vitamin D supplementation (BEST-D trial). During the trial they collect blood samples for functional genomic analysis by SNPO genotyping and microarray gene expression profiling. |
| Impact | Manuscript in preparation |
| Start Year | 2014 |
| Description | Proj 044 (Basson) |
| Organisation | King's College London |
| Department | MRC Centre for Developmental Neurobiology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Improving and optimizing the analysis of highly complex Capture Hi-C datasets. Integrating Capture Hi-C data with other functional genomic datasets (RNAseq, ChIPseq, ATACseq) and genetic variation data to understand the role of genetic variation in cerebellar hypoplasia. |
| Collaborator Contribution | Performing capture Hi-C in human cell lines and mouse neuronal tissue. Performing RNAseq, CHIPseq and ATAC-seq in the same systems. |
| Impact | Analysis ongoing |
| Start Year | 2015 |
| Description | Proj 045 (Jackson) |
| Organisation | Medical Research Council (MRC) |
| Department | MRC Human Genetics Unit |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Performing statistical analysis of genome wide genotyping data from the UK biobank project. Performed GWAS on red hair colour and blonde hair colour. Looking for genetic structure and interactions. Annotation of non-coding regions to identify the true cause of GWAS hits. |
| Collaborator Contribution | Our partners are acknowledged world leaders in genetic and functional analysis of pigmentation genes using mouse as a model system. They are very well set up to translate any in silico findings into functional experiments in the mouse. They have adopted Cas9/CRISPR technologies extremely successfully, and have introduced several point mutations by direct injection into mouse embryos, including modelling human MC1R variation in the mouse. They have also been granted access to UK Biobank data, including all genotypes and relevant phenotypes. |
| Impact | Manuscript in preparation |
| Start Year | 2015 |
| Description | Proj 046 (Jenner) |
| Organisation | University College London |
| Department | UCL Cancer Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Characterization of T cell eRNAs in human and mouse by integrating RNAseq, ChIPseq and other functional genomic datasets. The identification of exact transcription start and stop sites and the identification of conserved sequence or structural elements that can then be tested functionally by mutation. |
| Collaborator Contribution | Our partners are currently focused on the roles of master regulator transcription factors and non-coding RNAs in ES and T cell differentiation. They have gave generated a large number of genomic datsets including total and PolyA+ strand-specific RNA-Seq in human Th1 and Th2 cells, ChIP-Seq data for T-bet, RNA pol II, P-TEFb, H3K27ac, H3K4me3, H3K27me3 in primary human and mouse Th1 and Th2 cells, in mouse T-bet-/- cells and in a cell line expressing T-bet or GRP control. They have generated mouse total RNA-Seq data for comparison to human. They are also performing iClip for a number of proteins that may interact with eRNAs and these data will also be available. |
| Impact | Awaiting validation |
| Start Year | 2015 |
| Description | Proj 047 (Schuh) |
| Organisation | University of Oxford |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | CGAT will contribute experience in RNAseq data analysis; assistance with acquired (somatic) mutation analyses from RNA, quantitative expression analysis, analysis of non-coding RNA, quantification of non-coding RNA, quantification of RNA remnants, analysis of non-human RNA to look for possible viral genomes, correlation of DNA and RNA results. |
| Collaborator Contribution | Sequencing of germline and tumour DNA and tumour RNA from a cohort of chronic lymphocytic leukemia. Replication of findings in other cohorts. |
| Impact | 10.1038/leu.2016.307 |
| Start Year | 2014 |
| Description | Proj 048 (Gale) |
| Organisation | University College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Calling of variants from exome sequencing data, systematic pathway and analyses. |
| Collaborator Contribution | The primary hypothesis is that rare genetic variants make an important contribution to kidney disease in the UK population, and the scientific question is to identify the genes and variants responsible. Our partners have sequencing the exomes from tens of cases of kidney disease of unknown origin. |
| Impact | Manuscript in preparation |
| Start Year | 2015 |
| Description | Proj 049 (Ebner) |
| Organisation | University of Oxford |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Design of a genome-wide library of synthetic guide RNA targeting splice sites and other regions of functional importance. |
| Collaborator Contribution | Our partners will synthesis a set of sgRNAs we have designed and test them in a range of different assays, with known outcomes. They will optimise the combination of contructs to create a library that can be used for well based loss of function screening. |
| Impact | Awaiting validation |
| Start Year | 2015 |
| Description | Proj 050 (Talbot) |
| Organisation | University of Oxford |
| Department | Nuffield Department of Clinical Neurosciences |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | This project has been analysed by a PhD student in Prof Talbot's lab as part of a three month internship in CGAT. He has performed analysis of differential expression, differential splicing and analysis of CLIPseq data for TDP-43. |
| Collaborator Contribution | Our partners have generated a new BAC transgenic mutant TDP-43 mouse model with physiologically relevant TDP-43 expression and performed prospective longitudinal RNA-Seq to investigate the earliest transcriptional changes in relation to pathology in order to illuminate the pre-clinical biological landscape of disease. |
| Impact | Manuscript in preparation |
| Start Year | 2015 |
| Description | Proj 051 (Vatish) |
| Organisation | University of Oxford |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Analysis of differential expression of RNA, small RNA and protein in placenta, microvesicles and exosomes from normal and pre-eclampsia placentas. |
| Collaborator Contribution | Our partners prepared samples of placenta and placental microvesicles from cohorts of healthy women and with pre-eclampsia. |
| Impact | Analysis ongoing |
| Start Year | 2015 |
| Description | Proj 053 (Ansorge) |
| Organisation | University of Oxford |
| Department | Nuffield Department of Clinical Neurosciences |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Integration of exome sequencing, RNA-seq and methylation data with accompanying clinical data. |
| Collaborator Contribution | Our partners have generated exome sequencing data from tumour and non-tumour tissue, tumour RNA-seq data and Illumina's Infinium 450k methylome array data from 14 cases of somatotroph adenoma. To accompany the tissue they have extensive clinical/specimen records. Our partners will validate candidate causitive mutations by Sanger sequencing and perform relevant functional studies. |
| Impact | Analysis ongoing. |
| Start Year | 2015 |
| Description | Proj 054 (Simmons) |
| Organisation | University of Oxford |
| Department | Weatherall Institute of Molecular Medicine (WIMM) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Single cell RNA-seq data interpretation and cross-analysis of mucosal T cell populations in health and during disease. |
| Collaborator Contribution | Our partners are performing single cell transcriptomic profiling of intestinal T lymphocytes in health and during infection with Salmonella. |
| Impact | Data being generated. |
| Start Year | 2015 |
| Description | Proj 056 (Hollander) |
| Organisation | University of Oxford |
| Department | Weatherall Institute of Molecular Medicine (WIMM) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Analysis of scRNA seq data, intellectual input to drive project to publication |
| Collaborator Contribution | sample generation |
| Impact | Ongoing analysis |
| Start Year | 2015 |
| Description | Projs 009 & 021 (Hollaender) |
| Organisation | University of Basel |
| Department | Biozentrum Basel |
| Country | Switzerland |
| Sector | Academic/University |
| PI Contribution | Integration of multiple data sources from different biological materials in order to define TEC sub-populations and characterize Aire-independent transcription. Research question focuses on: analysis of the complexity of promiscuous gene expression in thymic epithelial cells. |
| Collaborator Contribution | Expertise in TEC biology; provision of data for analysis (RNA-Seq, miRNA, DNA methylation). |
| Impact | Paper: Population and single cell genomics reveal the Aire-dependency, relief from Polycomb silencing and distribution of self-antigen expression in thymic epithelia. Sansom SN, Shikama N, Zhanybekova S, Nusspaumer G, Macaulay IC, Deadman ME, Heger A, Ponting CP, Holländer GA. 2014 Sep 15. |
| Start Year | 2011 |