A5085476353- Single-cell and spatial transcriptomics
- Bioinformatics and Genomic Networks
- Genomics and Rare Diseases
- Computational Drug Discovery Methods
- Gene Regulatory Network Analysis
- Congenital gastrointestinal and neural anomalies
- Cell Image Analysis Techniques
- Cardiomyopathy and Myosin Studies
- Digestive system and related health
- Infant Nutrition and Health
- Muscle Physiology and Disorders
- Pluripotent Stem Cells Research
- Biotin and Related Studies
- Receptor Mechanisms and Signaling
- Genomics and Phylogenetic Studies
- Protein Structure and Dynamics
- Redox biology and oxidative stress
- Pancreatic function and diabetes
- Cellular Mechanics and Interactions
- Microbial Metabolic Engineering and Bioproduction
- RNA and protein synthesis mechanisms
- Nuclear Structure and Function
- Gut microbiota and health
- 3D Printing in Biomedical Research
- Renal and related cancers
The Francis Crick Institute
2021-2025
King's College London
2016-2021
Abstract Biology has become a data-intensive science. Recent technological advances in single-cell genomics have enabled the measurement of multiple facets cellular state, producing datasets with millions observations. While these data hold great promise for understanding molecular mechanisms health and disease, analysis challenges arising from sparsity, technical biological variability, high dimensionality hinder derivation such mechanistic insights. To promote innovation algorithms...
Abstract Glial cells have been proposed as a source of neural progenitors, but the mechanisms underpinning neurogenic potential adult glia are not known. Using single cell transcriptomic profiling, we show that enteric glial represent state attained by autonomic crest they transition along linear differentiation trajectory allows them to retain while acquiring mature functions. Key loci in early nervous system progenitors remain open chromatin configuration glia, thus facilitating neuronal...
Large cohorts of human induced pluripotent stem cells (iPSCs) from healthy donors are a potentially powerful tool for investigating the relationship between genetic variants and cellular behavior. Here, we integrate high content imaging cell shape, proliferation, other phenotypes with gene expression DNA sequence datasets over 100 iPSC lines. By applying dimensionality reduction approach, Probabilistic Estimation Expression Residuals (PEER), extracted factors that captured effects intrinsic...
The organs of many female animals are remodeled by reproduction. Using the mouse intestine, a striking and tractable model organ resizing, we find that reproductive remodeling is anticipatory distinct from diet- or microbiota-induced resizing. Reproductive involves partially irreversible elongation small intestine fully reversible growth its epithelial villi, associated with an expansion isthmus progenitors accelerated enterocyte migration. We identify induction SGLT3a transporter in subset...
Abstract Summary Large numbers of rare and unique titin missense variants have been discovered in both healthy disease cohorts, thus the correct classification as pathogenic or non-pathogenic has become imperative. Due to titin’s large size (363 coding exons), current web applications are unable map domain structures. Here, we present a application, TITINdb, which integrates structure, variant, sequence isoform information, along with pre-computed predictions impact non-synonymous single...
Missense variants are present amongst the healthy population, but some of them causative human diseases. A classification associated with “healthy” or “diseased” states is therefore not always straightforward. deeper understanding nature missense in health and disease, cellular processes they may affect, general molecular principles which underlie these differences essential to offer mechanistic explanations true impact pathogenic variants. Here, we have formalised a statistical framework...
Quantitative analysis of human induced pluripotent stem cell (iPSC) lines from healthy donors is a powerful tool for uncovering the relationship between genetic variants and cellular behavior. We previously identified rare, deleterious non-synonymous single nucleotide (nsSNVs) in adhesion genes that are associated with outlier iPSC phenotypes state. Here, we generated micropatterned colonies iPSCs to test whether nsSNVs influence patterning radially ordered germ layers. Using custom-built...
Abstract How neurogenesis and gliogenesis are coordinated during development why mature glial cells often share properties with neuroectodermal progenitors remains unclear. Here, we have used single cell RNA sequencing to map the regulatory landscape of neuronal differentiation in mammalian enteric nervous system (ENS). Our analysis indicates that neurogenic trajectories branch directly from a linear gliogenic axis defined by autonomic neural crest adopting sequential states as they...
Abstract Recent advances in biotechnologies for genomics and proteomics have expanded our understanding of biological components which play crucial roles complex mechanisms related to cancer. However, it is still challenging extract from the available knowledge reliable targets use a translational setting. The reasons this are manifold, but essentially distilling real signal heterogeneous “big data” collections major hurdle. Here, we aim establish an in-silico pipeline explore mutations...
Linear thresholding systems have been used as a model of neural activation and more recently proposed gene regulation. Here we exhibit linear whose dynamics produce surprisingly long cycles.
A bstract Differentiation of multipotential progenitor cells is a key process in the development any multi-cellular organism and often continues throughout its life. It assumed that bi-potential develops along (relatively) straight trajectory until it reaches decision point where bifurcates. At this one two directions chosen, each direction representing unfolding new transcriptomic programme. However, we have lacked quantitative means for testing model. Accordingly, developed R package...
Abstract Differentiation of multipotential progenitor cells is a key process in the development any multi-cellular organism and often continues throughout its life. It assumed that bi-potential develops along (relatively) straight trajectory until it reaches decision point where bifurcates. At this one two directions chosen, each direction representing unfolding new transcriptional programme. However, we have lacked quantitative means for testing model. Accordingly, developed R package...
Abstract Large cohorts of human iPSCs from healthy donors are potentially a powerful tool for investigating the relationship between genetic variants and cellular phenotypes. Here we integrate high content imaging, gene expression DNA sequence datasets over 100 iPSC lines to identify basis inter-individual variability in cell behaviour. By applying dimensionality reduction approach, Probabilistic Estimation Expression Residuals (PEER), identified genes that correlated with intrinsic...
Abstract Development of the nervous system is underpinned by changes in gene expression and chromatin configuration during embryogenesis early postnatal life. To uncover molecular mechanisms orchestrating cell lineage differentiation maturation enteric (ENS), we profiled transcriptome accessibility autonomic neural crest cells (ANCCs) their progeny mouse gut at key developmental stages adulthood. Integrative analyses defined a trajectory delineated ENS progenitors transitioning development...
Linear thresholding systems have been used as a model of neural activation and more recently proposed gene activation. Deterministic linear can be turned into non-deterministic by the introduction noise. Under mild conditions on noise, we show that deterministic deduced from probabilities model.
1 Abstract Missense variants are present amongst the healthy population, but some of them causative human diseases. Therefore, a classification associated with “healthy” or “diseased” states is not always straightforward. A deeper understanding nature missense in health and disease, cellular processes they may affect, general molecular principles which underlie these differences, essential to better distinguish pathogenic from population variants. Here we quantify variant enrichment across...