Colin A. Semple
A5034298865- Cancer Genomics and Diagnostics
- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Chromosomal and Genetic Variations
- RNA Research and Splicing
- BRCA gene mutations in cancer
- Genetic Associations and Epidemiology
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- Ovarian cancer diagnosis and treatment
- Genomics and Phylogenetic Studies
- Genetics, Bioinformatics, and Biomedical Research
- Cancer-related molecular mechanisms research
- Genomics and Rare Diseases
- Bioinformatics and Genomic Networks
- RNA modifications and cancer
- Genomic variations and chromosomal abnormalities
- Evolution and Genetic Dynamics
- Genetics and Neurodevelopmental Disorders
- Ubiquitin and proteasome pathways
- Genetic factors in colorectal cancer
- PARP inhibition in cancer therapy
- Endoplasmic Reticulum Stress and Disease
- Gene expression and cancer classification
University of Edinburgh
2016-2025
Institute of Genetics and Cancer
2016-2025
Western General Hospital
2012-2025
Medical Research Council
2001-2024
Edinburgh Cancer Research
2023
Institute of Cancer Research
2020
MRC Human Genetics Unit
2001-2019
University of Cambridge
2018
Google (United States)
2017
University of Turku
2012-2013
Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There an international collaborative effort to identify all full-length mRNA transcripts from mouse, and ensure that each represented in physical collection clones. Here we report manual annotation 60,770 complementary DNA sequences. These are clustered 33,409 'transcriptional units', contributing 90.1% newly established transcriptome database. Of these transcriptional units, 4,258 new...
A balanced (1;11)(q42.1;q14.3) translocation segregates with schizophrenia and related psychiatric disorders in a large Scottish family (maximum LOD = 6.0). We hypothesize that the is causative event it directly disrupts gene function. previously reported dearth of genes breakpoint region chromosome 11 therefore unlikely expression any on this has been affected by translocation. By contrast, corresponding 1 dense and, not one, but two novel are disrupted These have provisionally named...
<b>Objective</b> To determine whether aspirin and antioxidant therapy, combined or alone, are more effective than placebo in reducing the development of cardiovascular events patients with diabetes mellitus asymptomatic peripheral arterial disease. <b>Design</b> Multicentre, randomised, double blind, 2×2 factorial, controlled trial. <b>Setting</b> 16 hospital centres Scotland, supported by 188 primary care groups. <b>Participants</b> 1276 adults aged 40 type 1 2 an ankle brachial pressure...
The manuscript describes the "digital transcriptome atlas" of developing mouse embryo, a powerful resource to determine co-expression genes, identify cell populations and lineages functional associations between genes relevant development disease.
Article28 December 2015Open Access Hierarchical folding and reorganization of chromosomes are linked to transcriptional changes in cellular differentiation James Fraser Department Biochemistry, Goodman Cancer Centre, McGill University, Montréal, QC, Canada Search for more papers by this author Carmelo Ferrai Epigenetic Regulation Chromatin Architecture Group, Berlin Institute Medical Systems Biology, Max-Delbrück Centre Molecular Medicine, Berlin-Buch, Germany Genome Function MRC Clinical...
We recently found that hnRNP A1, a protein implicated in many aspects of RNA processing, acts as an auxiliary factor for the Drosha-mediated processing microRNA precursor, pri-miR-18a. Here, we provide mechanism by which A1 regulates this event. show binds to loop pri-miR-18a and induces relaxation at stem, creating more favorable cleavage site Drosha. approximately 14% all pri-miRNAs have highly conserved loops, predict act landing pads trans-acting factors influencing miRNA processing. In...
Evolutionary change in gene expression is generally considered to be a major driver of phenotypic differences between species. We investigated innate immune diversification by analyzing interspecies the transcriptional responses primary human and mouse macrophages Toll-like receptor (TLR)–4 agonist lipopolysaccharide (LPS). By using custom platform permitting cross-species interrogation coupled with deep sequencing mRNA 5′ ends, we identified extensive divergence LPS-regulated orthologous...
Abstract In cancer, the primary tumour’s organ of origin and histopathology are strongest determinants its clinical behaviour, but in 3% cases a patient presents with metastatic tumour no obvious primary. Here, as part ICGC/TCGA Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium , we train deep learning classifier to predict cancer type based on patterns somatic passenger mutations detected whole genome sequencing (WGS) 2606 tumours representing 24 common types produced by PCAWG...
Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in mammalian genomes, and yet, their functions remain largely unknown. As part FANTOM6 project, we systematically knocked down expression 285 lncRNAs human dermal fibroblasts quantified cellular growth, morphological changes, transcriptomic responses using Capped Analysis Gene Expression (CAGE). Antisense oligonucleotides targeting same exhibited global concordance, molecular phenotype, measured by CAGE, recapitulated...
Here we present POCUS (prioritization of candidate genes using statistics), a novel computational approach to prioritize disease that is based on over-representation functional annotation between loci for the same disease. We show can provide high (up 81-fold) enrichment real in candidate-gene shortlists it produces compared with original large sets positional candidates. In contrast existing methods, also suggest counterintuitive
Completion of meiosis in mammals depends on the formation synaptonemal complex, a tripartite structure that physically links homologous chromosomes during prophase I. Several components complex are known, including constituents cohesin core, axial/lateral element and transverse filaments. No protein has previously been identified as an exclusive component central element. Mutations some synaptonemal-complex proteins results impaired meiosis. In humans, cases male infertility have associated...
BackgroundGermline variation in the 71 Crohn's disease (CD) loci implicated by genome-wide association studies (GWAS) only accounts for approximately 25% of estimated heritability. The contribution epigenetic alterations to pathogenesis is emerging as a research priority.
Gametogenesis is a complex process subject to strict controls at both levels of transcription and translation. Members family conserved RNA-binding proteins encoded by the DAZ genes are required for translational regulation gene expression essential this process. Although loss associated with infertility in several organisms including humans, identity transcripts regulated vivo unknown. Using combination immunoprecipitation microarray analysis, we have identified number mRNAs that bound...
β-Defensins are cationic host defense peptides that form an amphipathic structure stabilized by three intramolecular disulfide bonds. They key players in innate and adaptive immunity have recently been shown to limit the production of pro-inflammatory cytokines TLR4-stimulated macrophages. In present study, we investigate mechanism underlying anti-inflammatory effect human β-defensin 3 (hBD3). We show canonical hBD3 is required for this immunosuppressive rapidly associates with enters...
Naturally occurring regulatory T (Treg) cells, which specifically express the transcription factor forkhead box P3 (Foxp3), are engaged in maintenance of immunological self-tolerance and homeostasis. By transcriptional start site cluster analysis, we assessed here how genome-wide patterns DNA methylation or Foxp3 binding sites were associated with Treg-specific gene expression. We found that hypomethylated regions closely Treg up-regulated clusters, whereas had no significant correlation...
Abstract Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, most cancers outside the sex organs. Efforts to link these clinical specific molecular features focused on somatic mutations within coding regions genome. Here we report a pan-cancer analysis whole genomes 1983 tumours 28 subtypes as part ICGC/TCGA Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium. We both confirm results exome studies, also uncover previously undescribed...
Endometrioid ovarian carcinoma (EnOC) demonstrates substantial clinical and molecular heterogeneity. Here, we report whole exome sequencing of 112 EnOC cases following rigorous pathological assessment. We detect a high frequency mutation in CTNNB1 (43%), PIK3CA ARID1A (36%), PTEN (29%), KRAS (26%), TP53 (26%) SOX8 (19%), recurrently-mutated gene previously unreported EnOC. POLE mismatch repair protein-encoding genes were mutated at lower (6%, 18%) with significant co-occurrence. A taxonomy...
Abstract DNA base damage is a major source of oncogenic mutations 1 . Such can produce strand-phased mutation patterns and multiallelic variation through the process lesion segregation 2 Here we exploited these properties to reveal how strand-asymmetric processes, such as replication transcription, shape repair. Despite distinct mechanisms leading lagging strand 3,4 , observe identical fidelity tolerance for both strands. For small alkylation adducts DNA, our results support model in which...