A5072182550- Phosphodiesterase function and regulation
- Computational Drug Discovery Methods
- Bioinformatics and Genomic Networks
- Inflammatory Bowel Disease
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Helicobacter pylori-related gastroenterology studies
- Receptor Mechanisms and Signaling
- Tuberculosis Research and Epidemiology
- Pharmacogenetics and Drug Metabolism
- Biosimilars and Bioanalytical Methods
- Business and Economic Development
- MicroRNA in disease regulation
- Metabolomics and Mass Spectrometry Studies
- Celiac Disease Research and Management
- Drug-Induced Hepatotoxicity and Protection
- Protein Tyrosine Phosphatases
- Genetic Syndromes and Imprinting
- Global Healthcare and Medical Tourism
- Renal Diseases and Glomerulopathies
- Plant-based Medicinal Research
- Machine Learning in Materials Science
- GDF15 and Related Biomarkers
University of Cambridge
2017-2024
Unilever (United Kingdom)
2016
Université Claude Bernard Lyon 1
2013
Laboratoire de Physique de l'ENS de Lyon
2013
École Normale Supérieure de Lyon
2013
In this work, we present eMolTox, a web server for the prediction of potential toxicity associated with given molecule. A total 174 toxicology-related in vitro/vivo experimental datasets were used model construction and Mondrian conformal was to estimate confidence resulting predictions. Toxic substructure analysis is also implemented eMolTox. eMolTox predicts displays wealth information molecular toxicities safety drug development.The Server freely available use on at...
Advances in genomic studies have led to significant progress understanding the epigenetically controlled interplay between chromatin structure and nuclear functions. Epigenetic modifications were shown play a key role transcription regulation genome activity during development differentiation or response environment. Paradoxically, molecular mechanisms that regulate initiation maintenance of spatio-temporal replication program higher eukaryotes, particular their links epigenetic...
One important, however, poorly understood, concept of Traditional Chinese Medicine (TCM) is that hot, cold, and neutral nature its bioactive principles. To advance the field, in this study, we analyzed compound-nature pairs from TCM on a large scale (>23 000 structures) via chemical space visualizations to understand physicochemical domain silico target prediction differences related their modes-of-action (MoA) against proteins. We found overall natures spread into different subclusters with...
We describe a precision medicine workflow, the integrated single nucleotide polymorphism network platform (iSNP), designed to determine mechanisms by which SNPs affect cellular regulatory networks, and how SNP co-occurrences contribute disease pathogenesis in ulcerative colitis (UC). Using profiles of 378 UC patients we map effects human signalling containing protein-protein, miRNA-mRNA transcription factor binding interactions. With unsupervised clustering algorithms group these...
Compounds designed to display polypharmacology may have utility in treating complex diseases, where activity at multiple targets is required produce a clinical effect. In particular, suitable compounds be useful neurodegenerative diseases by promoting neuronal survival synergistic manner via their multi-target the adenosine A1 and A2A receptors (A1R A2AR) phosphodiesterase 10A (PDE10A), which modulate intracellular cAMP levels. Hence, this work we describe computational method for design of...
Autosomal dominant polycystic kidney disease (ADPKD) is a rare genetic disorder characterised by numerous renal cysts, the progressive expansion of which can impact function and lead eventually to failure. Tolvaptan only disease-modifying drug approved for treatment ADPKD, however its poor side effect safety profile necessitates need development new therapeutics in this area. Using combination transcriptomic machine learning computational discovery tools, we predicted that number existing...
Increasing knowledge of chromatin structure in various cell types raises the challenge deciphering contribution epigenetic modifications to regulation nuclear functions mammals. In a recent study, we have analysed genome-wide distributions thirteen marks human line K562 at 100 kb resolution Mean Replication Timing (MRT) data. Using classical clustering techniques, shown that combinatorial complexity these data can be reduced four predominant states replicate different periods S-phase. C1 is...
Similarity between the ligand binding profiles of enzymes may aid functional characterization and be greater relevance to inhibitor development than sequence similarity or structural homology. Fragment screening is an efficient approach for profile enzyme has been applied here study family cytochrome P450 (P450s) expressed by Mycobacterium tuberculosis (Mtb). The Mtb P450s have important roles in bacterial virulence, survival, pathogenicity. Comparing fragment seven these revealed that which...
Current in vitro models for hepatotoxicity commonly suffer from low detection rates due to incomplete coverage of bioactivity space. Additionally, vivo exposure measures such as Cmax are used screening and unavailable early on. Here we propose a novel rule-based framework extract interpretable biologically meaningful multiconditional associations prioritize end points understand the associated physicochemical conditions. The data this study were derived 673 compounds 361 ToxCast measurements...
Adverse events resulting from drug therapy can be a cause of withdrawal, reduced and or restricted clinical use, as well major economic burden for society. To increase the safety new drugs, there is need to better understand mechanisms causing adverse events. One way derive mechanistic hypotheses by linking data on with drugs' biological targets. In this study, we have used mining techniques mutual information statistical approaches find associations between reported collected FDA Event...
Abstract Genome-wide association studies have pinpointed numerous susceptibility loci in complex diseases like chronic immune-mediated inflammatory disorders (IMIDs), yet their impact on pathomechanisms remain poorly understood. Genetic epistasis, low effect sizes, and predominance within non-coding genomic regions, major challenges to the functional interpretation of IMID-associated single nucleotide polymorphisms (SNPs). To address this, we present a novel systems genomics approach which...
Abstract We describe a novel precision medicine workflow, the integrated single nucleotide polymorphism network platform (iSNP), designed to identify exact mechanisms of how SNPs affect cellular regulatory networks, and SNP co-occurrences contribute disease pathogenesis in ulcerative colitis (UC). Using profiles 377 UC patients, we mapped effects human signalling containing protein-protein, miRNA-mRNA transcription factor binding interactions. Unsupervised clustering algorithms grouped these...
ulcerative colitis (UC) is a complex disease with poorly understood pathogenesis. In recent years, enormous genome-wide association studies have identified 242 single-nucleotide polymorphisms (SNPs) which cause UC susceptibility. However, their exact functions and effects remain unknown. To help discover novel pathogenic pathways in UC, we developed network biology approaches to study these SNPs the context of signalling regulatory landscapes. We used immunochip profiles 941 patients...
The pathogenic signalling pathways of ulcerative colitis (UC) are complex, making patient stratification for optimal therapeutic choices challenging. Disease associated single-nucleotide polymorphisms (SNPs) make the prospect personalised disease and therapeutics tantalisingly plausible, but forward movement has been difficult. Using systems genomics, we propose a method to identify cohort-specific patient-specific targetable pathways. UC-associated SNPs from UKIBD Genetics Consortium Broad...
Abstract Background Genome-wide association studies have deciphered the single nucleotide polymorphisms (SNPs) which are responsible for ulcerative colitis (UC) susceptibility. However, to understand how these SNPs involved in UC, additional methods necessary. One such approach is silico network propagation modelling, can discover effects of UC affect whole cell. A complementary weighted gene co-expression analysis (WGCNA), where co-regulated genes identified using transcriptomic data....