A5026422459- Epigenetics and DNA Methylation
- Bioinformatics and Genomic Networks
- Gene expression and cancer classification
- Complex Network Analysis Techniques
- Neuroscience and Neuropharmacology Research
- Single-cell and spatial transcriptomics
- Gene Regulatory Network Analysis
- Statistical Methods and Inference
- Memory and Neural Mechanisms
- Neural dynamics and brain function
- Complex Systems and Time Series Analysis
- RNA modifications and cancer
- Opinion Dynamics and Social Influence
- Genetic Syndromes and Imprinting
- Time Series Analysis and Forecasting
- CRISPR and Genetic Engineering
- Ion channel regulation and function
- Mental Health Research Topics
- Chaos control and synchronization
- Breast Cancer Treatment Studies
- Ovarian cancer diagnosis and treatment
- Advanced Graph Neural Networks
- Genomics and Chromatin Dynamics
- Nerve injury and regeneration
- Stock Market Forecasting Methods
University College London
2013-2024
University College Hospital
2016
University of British Columbia
2010-2013
Karolinska Institutet
2012
Vancouver Coastal Health
2010
Vancouver Coastal Health Research Institute
2010
University of Bristol
2006
Abstract Motivation: The Illumina Infinium 450 k DNA Methylation Beadchip is a prime candidate technology for Epigenome-Wide Association Studies (EWAS). However, difficulty associated with these beadarrays that probes come in two different designs, characterized by widely methylation distributions and dynamic range, which may bias downstream analyses. A key statistical issue therefore how best to adjust the probe designs. Results: Here we propose novel model-based intra-array normalization...
Glioblastoma (GBM) is an aggressive brain tumor whose growth driven by stem cell-like cells. BMP signaling triggers cell-cycle exit and differentiation of GBM cells (GSCs) and, therefore, might have therapeutic value. However, the epigenetic mechanisms that accompany remain poorly defined. It also unclear whether arrest terminal. Here we find only a subset GSC cultures exhibit astrocyte in response to BMP. Although overtly differentiated non-cycling astrocytes are generated, they vulnerable...
The cadherin/β-catenin adhesion complex is a key mediator of the bidirectional changes in synapse strength which are believed to underlie learning and memory. In present study, we demonstrate that stabilization β-catenin hippocampus adult mice results significant impairments cognitive flexibility spatial reversal learning, including impaired extinction during phase Morris water maze deficits delayed nonmatch place T-maze task. accordance with these deficits, was found abolish long-term...
Abstract The exact timing and contribution of epigenetic reprogramming to carcinogenesis are unclear. Women harbouring BRCA1/2 mutations demonstrate a 30–40-fold increased risk high-grade serous extra-uterine Müllerian cancers (HGSEMC), otherwise referred as ‘ovarian carcinomas’, which frequently develop from fimbrial cells but not the proximal portion fallopian tube. Here we compare DNA methylome ends tube in mutation carriers non-carriers. We show that number CpGs displaying significant...
Recent advances in single-cell omics have transformed characterisation of cell types challenging-to-study biological contexts. In contexts with limited samples, such as the early human embryo inference transcription factor-gene regulatory network (GRN) interactions is especially difficult. Here, we assessed application different linear or non-linear GRN predictions to simulated and transcriptome datasets. We also compared how expression normalisation impacts on predictions, finding that...
Abstract Background Breast cancer is a leading cause of death in premenopausal women. Progesterone drives expansion luminal progenitor cells, to the development poor-prognostic breast cancers. However, it not known if antagonising progesterone can prevent cancers humans. We suggest that targeting signalling could be means reducing features which are promote formation. Methods In healthy women with and without BRCA mutation we studied (i) estrogen levels saliva over an entire menstrual cycle...
Epigenetic processes–including DNA methylation–are increasingly seen as having a fundamental role in chronic diseases like cancer. methylation patterns offer route to develop prognostic measures based directly on measurements, rather than less-stable RNA measurements. A novel methylation-based measure of the co-ordinated interactive behaviour genes is developed, network context. It shown that this reflects well co-regulatory linked gene expression (at mRNA level) over same interactions. This...
Epigenetic processes - including DNA methylation are increasingly seen as having a fundamental role in chronic diseases like cancer. It is well known that levels at particular genes or loci differ between normal and diseased tissue. Here we investigate whether the intra-gene architecture corrupted cancer variability of individual CpGs within defined gene able to discriminate cancerous from tissue, associated with heterogeneous tumour phenotype, by expression. We analysed 270985 annotated...
Abstract Single-cell transcriptomic data have rapidly become very popular in genomic science. Genomic science also has a long history of using network models to understand the way which genes work together carry out specific biological functions. However, working with single-cell presents major challenges, such as zero inflation and technical noise. These challenges require methods be specifically adapted context data. Recently, much effort been made develop theory behind statistical models....
We make use of ideas from the theory complex networks to implement a machine learning classification human DNA methylation data, that carry signatures cancer development. The data were obtained patients with various kinds cancers and represented as parenclictic networks, wherein nodes correspond genes, edges are weighted according pairwise variation control group subjects. demonstrate for 10 types under study, it is possible obtain high performance binary between cancer-positive negative...
We introduce a novel per-gene measure of intra-gene DNA methylation variability (IGV) based on the Illumina Infinium HumanMethylation450 platform, which is prognostic independently well-known predictors clinical outcome. Using IGV, we derive robust gene-panel signature for ovarian cancer (OC, n = 221), validates in two independent data sets from Mayo Clinic (n 198) and TCGA 358), with significance p 0.004 both sets. The OC comprised four gene groups, represent distinct biological processes....
Abstract Background A variety of epigenetic clocks utilizing DNA methylation changes have been developed; these are either tissue-independent or designed to predict chronological age based on blood saliva samples. Whether discordant tick rates between tissue-specific and general play a role in health disease has not yet explored. Results Here we analyze 1941 cervical cytology samples, which contain mixture hormone-sensitive epithelial cells immune cells, develop the WID clock (Women’s...
The contribution of different GluN2 subunits the N-methyl D-aspartate (NMDA) receptor to induction bidirectional hippocampal synaptic plasticity is a controversial topic. As both supporting and refuting evidence for hypothesis subunit specialization in opposing directions has accumulated since it was first proposed few years ago, we hypothesize that differences experimental conditions may have part contributed some inconsistent results from these studies. Here investigate long-term...
Abstract Recent advances in single-cell-omics have been transformative to characterise cell types challenging study biological contexts. It is technically difficult infer transcription factor-gene regulatory interactions from these datasets, especially contexts with limited single-cell sample number such as the early human embryo. Here we systematically assessed application of four different linear or non-linear gene network (GRN) prediction strategies simulated and embryo transcriptome...
In this paper we propose network methodology to infer prognostic cancer biomarkers based on the epigenetic pattern DNA methylation. Epigenetic processes such as methylation reflect environmental risk factors, and are increasingly recognised for their fundamental role in diseases cancer. is a gene-regulatory pattern, hence provides means by which assess genomic regulatory interactions. Network models natural way represent analyse groups of The utility also increases quantity data number...
In this article we propose methodology for inference of binary-valued adjacency matrices from various measures the strength association between pairs network nodes, or more generally variables. This can be quantified by sample covariance and correlation matrices, test-statistics hypothesis test p-values arbitrary distributions. Community detection methods such as block modeling typically require a starting point. Hence, main motivation is to obtain pairwise The proposed applicable large...
We propose a novel algorithm for testing the hypothesis of nonstationarity in complex-valued signals. The implementation uses both bootstrap and Fast Fourier Transform such that can be efficiently implemented O(NlogN) time, where N is length observed signal. test procedure examines second-order structure contrasts power variance -- i.e. variability instantaneous over time with expected characteristics stationary signals generated via method. Our algorithmic capable learning different types...
We propose a novel way of modelling time-varying networks by inducing two-way sparsity on local models node connectivity. This separately promotes across time and variables (within time). Separation these two types is achieved through prior structure which draws ideas from the Bayesian lasso copula modelling. provide an efficient implementation proposed model via Gibbs sampler, we apply to data neural development. In doing so, demonstrate that able identify changes in genomic network match...
Background: Tissue-specificity for fimbrial fallopian tube ovarian carcinogenesis remains largely unknown in BRCA1 mutation carriers. We aimed to assess the cell autonomous and cell-nonautonomous implications of a germline context cancer immunosurveillance CD3− CD56+ natural killer (NK) cells. Methods: Premenopausal carriers versus age-matched non-carriers were compared. Daily urinary 5β-pregnanediol levels used determine progesterone metabolomics across an cycle. Using peripherally acquired...