A5061470053- Cancer Genomics and Diagnostics
- Genomics and Phylogenetic Studies
- PARP inhibition in cancer therapy
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Glycosylation and Glycoproteins Research
- RNA modifications and cancer
- Microbial Community Ecology and Physiology
- Peptidase Inhibition and Analysis
- Single-cell and spatial transcriptomics
- Cancer-related gene regulation
- Chronic Lymphocytic Leukemia Research
- Genetics and Neurodevelopmental Disorders
- DNA Repair Mechanisms
- Molecular Biology Techniques and Applications
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Galectins and Cancer Biology
- Cell Image Analysis Techniques
- T-cell and B-cell Immunology
- Cancer-related molecular mechanisms research
- Gene expression and cancer classification
- Lung Cancer Treatments and Mutations
- Genetic factors in colorectal cancer
- Cancer-related Molecular Pathways
MRC Weatherall Institute of Molecular Medicine
2016-2024
John Radcliffe Hospital
2015-2024
University of Oxford
2015-2024
Oklahoma Christian University
2024
Science Oxford
2024
Frederick National Laboratory for Cancer Research
2015-2023
Medical Research Council
2013-2023
École Polytechnique Fédérale de Lausanne
2022
HudsonAlpha Institute for Biotechnology
2011-2021
Immunomedics (Germany)
2021
Summary Sorghum bicolor is a drought tolerant C4 grass used for the production of grain, forage, sugar, and lignocellulosic biomass genetic model grasses due to its relatively small genome (approximately 800 Mbp), diploid genetics, diverse germplasm, colinearity with other genomes. In this study, deep sequencing, linkage analysis, transcriptome data were produce annotate high‐quality reference sequence. Reference sequence order was improved, 29.6 Mbp additional incorporated, number genes...
CpG islands (CGIs) are associated with most mammalian gene promoters. A subset of CGIs act as polycomb response elements (PREs) and recognized by the silencing systems to regulate expression genes involved in early development. How function mechanistically nucleation sites for repressive complexes remains unknown. Here we discover that KDM2B (FBXL10) specifically recognizes non-methylated DNA recruits complex 1 (PRC1). This contributes histone H2A lysine 119 ubiquitylation (H2AK119ub1)...
Abstract Sugarcane ( Saccharum spp.) is a major crop for sugar and bioenergy production. Its highly polyploid, aneuploid, heterozygous, interspecific genome poses challenges producing reference sequence. We exploited colinearity with sorghum to produce BAC-based monoploid sequence of sugarcane. A minimum tiling path 4660 sugarcane BAC that best covers the gene-rich part was selected based on whole-genome profiling, sequenced, assembled in 382-Mb single high-quality total 25,316...
Nature Communications 5: Article number: 3979 (2014); Published 9 June 2014; Updated April 2015. The original version of this contained a typographical error in the spelling author Nicholas E. Ilott, which was incorrectly given as IIott. This has now been corrected both PDF and HTML versions Article.
Small-molecule inhibitors of PARP1/2, such as olaparib, have been proposed to serve a synthetic lethal therapy for cancers that harbor BRCA1 or BRCA2 mutations. Indeed, in clinical trials, PARP1/2 elicit sustained antitumor responses patients with germline BRCA gene In hypothesizing additional genetic determinants might direct use these drugs, we conducted genome-wide screen candidate olaparib sensitivity genes. support this hypothesis, the set identified genes included known sensitivity,...
Therapeutically actionable molecular alterations are widely distributed across cancer types. The National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial was designed to evaluate targeted therapy antitumor activity in underexplored Tumor biopsy specimens were analyzed centrally with next-generation sequencing (NGS) a master screening protocol. Patients tumor alteration addressed by treatment lacking established efficacy that type assigned 1 of 30 treatments parallel,...
Two-thirds of gene promoters in mammals are associated with regions non-methylated DNA, called CpG islands (CGIs), which counteract the repressive effects DNA methylation on chromatin. In cold-blooded vertebrates, computational CGI predictions often reside away from promoters, suggesting a major divergence promoter architecture across vertebrates. By experimentally identifying genomes seven diverse we instead reveal that (NMIs) central feature vertebrate promoters. Furthermore, NMIs present...
Abstract Background The proportion of tumors various histologies that may respond to drugs targeted molecular alterations is unknown. NCI-MATCH, a collaboration between ECOG-ACRIN Cancer Research Group and the National Institute, was initiated find efficacy signals by matching patients with refractory malignancies treatment potential tumor drivers regardless cancer histology. Methods Trial development required assumptions about target prevalence, accrual rates, eligibility, enrollment rates...
Long-term climate change and periodic environmental extremes threaten food fuel security1 global crop productivity2-4. Although molecular adaptive breeding strategies can buffer the effects of climatic stress improve resilience5, these approaches require sufficient knowledge genes that underlie productivity adaptation6-knowledge has been limited to a small number well-studied model systems. Here we present assembly annotation large complex genome polyploid bioenergy switchgrass (Panicum...
Androgen-deprivation therapy (ADT) is standard treatment for locally advanced or metastatic prostate cancer (PCa). Many patients develop castration resistance (castration-resistant PCa [CRPC]) after approximately 2-3 yr, with a poor prognosis. The molecular mechanisms underlying CRPC progression are unclear.
Abstract The design of targeted therapeutic strategies for cancer has largely been driven by the identification tumor-specific genetic changes. However, large number alterations present in tumor cells means that it is difficult to discriminate between genes are critical maintaining disease state and those merely coincidental. Even when can be identified, directly targeting these often challenging, meaning alternative such as exploiting synthetic lethality may beneficial. To address issues,...
Cerebral palsy is a sporadic disorder with multiple likely aetiologies, but frequently considered to be caused by birth asphyxia. Genetic investigations are rarely performed in patients cerebral and there little proven evidence of genetic causes. As part large project investigating children ataxia, we identified four our cohort diagnosis ataxic palsy. They were investigated using either targeted next generation sequencing or trio-based exome found have mutations three different genes, KCNC3,...
Therapies that target estrogen signaling have made a very considerable contribution to reducing mortality from breast cancer. However, resistance tamoxifen remains major clinical problem. Here we used genome-wide functional profiling approach identify multiple genes confer or sensitivity tamoxifen. Combining whole-genome shRNA screening with massively parallel sequencing, profiled the impact of more than 56,670 RNA interference reagents targeting 16,487 on cellular response This screen,...
Abstract RNA interference (RNAi) screening is a state-of-the-art technology that enables the dissection of biological processes and disease-related phenotypes. The commercial availability genome-wide, short hairpin (shRNA) libraries has fueled interest in this area but generation analysis these complex data remain challenge. Here, we describe complete experimental protocols novel open source computational methodologies, shALIGN shRNAseq, allow RNAi screens to be rapidly deconvoluted using...
Abstract Natural hair colour within European populations is a complex genetic trait. Previous work has established that MC1R variants are the principal cause of red colour, but with variable penetrance. Here, we have extensively mapped genes responsible for in white, British ancestry, participants UK Biobank. only explains 73% SNP heritability Biobank, and fact most individuals two blonde or light brown hair. We identify other contributing to hair, combined effect which accounts ~90%...
Late-onset ataxias are clinically and etiologically diverse. Patients rarely have defining clinical features, many remain classified as idiopathic, despite extensive clinical, metabolic, genetic investigations. Here we show that mutations in a gene known to cause hereditary spastic paraplegia ( SPG7 ) major of unexplained ataxia presenting mid-adult life.
During gene expression, RNA export factors are mainly known for driving nucleo-cytoplasmic transport. While early studies suggested that the exon junction complex (EJC) provides a binding platform them, subsequent work proposed they only recruited by cap to 5' end of RNAs, as part TREX. Using iCLIP, we show receptor Nxf1 and two TREX subunits, Alyref Chtop, whole mRNA co-transcriptionally via splicing but before 3' processing. Consequently, alters decisions Chtop regulates alternative...
Polymicrogyria is a malformation of cortical development. The aetiology polymicrogyria remains poorly understood. Using whole-exome sequencing we found de novo heterozygous missense GRIN1 mutations in 2 57 parent-offspring trios with polymicrogyria. We nine further additional patients. Shared features the patients were extensive bilateral associated severe developmental delay, postnatal microcephaly, visual impairment and intractable epilepsy. encodes GluN1, essential subunit...