A5005275806- Single-cell and spatial transcriptomics
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Gene expression and cancer classification
- Pluripotent Stem Cells Research
- Gene Regulatory Network Analysis
- Cancer Genomics and Diagnostics
- Cell Image Analysis Techniques
- Bioinformatics and Genomic Networks
- Congenital heart defects research
- Biomedical and Engineering Education
- Neonatal Respiratory Health Research
- Renal and related cancers
- Genomics and Phylogenetic Studies
- Chronic Lymphocytic Leukemia Research
- Gut microbiota and health
- RNA Research and Splicing
- Genetics, Bioinformatics, and Biomedical Research
- CRISPR and Genetic Engineering
- Bacteriophages and microbial interactions
- Drug-Induced Hepatotoxicity and Protection
- Vitamin C and Antioxidants Research
- Cancer Cells and Metastasis
- Rural development and sustainability
- Zebrafish Biomedical Research Applications
Babraham Institute
2021-2024
European Bioinformatics Institute
2017-2023
Granta Design (United Kingdom)
2022-2023
Cancer Research UK
2017
University of Cambridge
2017
Method20 June 2018Open Access Transparent process Multi-Omics Factor Analysis—a framework for unsupervised integration of multi-omics data sets Ricard Argelaguet orcid.org/0000-0003-3199-3722 European Molecular Biology Laboratory, Bioinformatics Institute, Hinxton, Cambridge, UK Search more papers by this author Britta Velten orcid.org/0000-0002-8397-3515 Laboratory (EMBL), Heidelberg, Germany Damien Arnol orcid.org/0000-0003-2462-534X Sascha Dietrich orcid.org/0000-0002-0648-1832 Heidelberg...
Abstract Parallel single-cell sequencing protocols represent powerful methods for investigating regulatory relationships, including epigenome-transcriptome interactions. Here, we report a method parallel chromatin accessibility, DNA methylation and transcriptome profiling. scNMT-seq (single-cell nucleosome, transcription sequencing) uses GpC methyltransferase to label open followed by bisulfite RNA sequencing. We validate applying it differentiating mouse embryonic stem cells, finding links...
Abstract Technological advances have enabled the profiling of multiple molecular layers at single-cell resolution, assaying cells from samples or conditions. Consequently, there is a growing need for computational strategies to analyze data complex experimental designs that include modalities and groups samples. We present Multi-Omics Factor Analysis v2 (MOFA+), statistical framework comprehensive scalable integration multi-modal data. MOFA+ reconstructs low-dimensional representation using...
Abstract Molecular profiling of single cells has advanced our knowledge the molecular basis development. However, current approaches mostly rely on dissociating from tissues, thereby losing crucial spatial context regulatory processes. Here, we apply an image-based single-cell transcriptomics method, sequential fluorescence in situ hybridization (seqFISH), to detect mRNAs for 387 target genes tissue sections mouse embryos at 8–12 somite stage. By integrating and multiplexed transcriptional...
The activation of the embryonic genome marks first major wave transcription in developing organism. Zygotic (ZGA) mouse 2-cell embryos and 8-cell humans is crucial for development. Here, we report discovery human 8-cell-like cells (8CLCs) among naive stem cells, which transcriptionally resemble embryo. They express ZGA markers, including ZSCAN4 LEUTX, transposable elements, such as HERVL MLT2A1. 8CLCs show reduced SOX2 levels can be identified using TPRX1 H3.Y marker proteins vitro....
Factor analysis is a widely used method for dimensionality reduction in genome biology, with applications from personalized health to single-cell biology. Existing factor models assume independence of the observed samples, an assumption that fails spatio-temporal profiling studies. Here we present MEFISTO, flexible and versatile toolbox modeling high-dimensional data when spatial or temporal dependencies between samples are known. MEFISTO maintains established benefits multimodal data, but...
Bacterial microbiota play a critical role in mediating local and systemic immunity, shifts these microbial communities have been linked to impaired outcomes illness. Emerging data indicate that other intestinal organisms, including bacteriophages, viruses of eukaryotes, fungi, protozoa, are closely interlinked with the bacterial their host, yet collective during antibiotic perturbation illness remains be elucidated. We employed multi-omics factor analysis (MOFA) systematically integrate (16S...
Abstract Following gastrulation, the three primary germ layers develop into major organs in a process known as organogenesis. Single-cell RNA sequencing has enabled profiling of gene expression dynamics these cell fate decisions, yet comprehensive map interplay between transcription factors and cis-regulatory elements is lacking, are underlying regulatory networks. Here we generate multi-omics atlas mouse early organogenesis by simultaneously chromatin accessibility from tens thousands...
Early organogenesis represents a key step in animal development, during which pluripotent cells diversify to initiate organ formation. Here, we sampled 300,000 single-cell transcriptomes from mouse embryos between E8.5 and E9.5 6-h intervals combined this new dataset with our previous atlas (E6.5-E8.5) produce densely timecourse of >400,000 early gastrulation organogenesis. Computational lineage reconstruction identified complex waves blood endothelial including programme for somite-derived...
Perturbation of DNA methyltransferases (DNMTs) and the active demethylation pathway via ten-eleven translocation (TET) methylcytosine dioxygenases results in severe developmental defects embryonic lethality. Dynamic control methylation is therefore vital for embryogenesis, yet underlying mechanisms remain poorly understood.
Abstract Transcriptional and epigenetic profiling of single-cells has advanced our knowledge the molecular bases gastrulation early organogenesis. However, current approaches rely on dissociating cells from tissues, thereby losing crucial spatial context that is necessary for understanding cell tissue interactions during development. Here, we apply an image-based single-cell transcriptomics method, seqFISH, to simultaneously precisely detect mRNA molecules 387 selected target genes in 8-12...
Abstract Recent advances in organoid and genome editing technologies are allowing for perturbation experiments at an unprecedented scale. However, before doing such it is important to understand the gene expression profile each of organoid’s cells, as well how much heterogeneity there between individual organoids. Here we characterise model mouse gastrulation called gastruloids using single cell RNA-sequencing organoids half-day intervals day 3 5 differentiation (roughly corresponding...
High-throughput single-cell measurements of DNA methylomes can quantify methylation heterogeneity and uncover its role in gene regulation. However, technical limitations sparse coverage preclude this task. scMET is a hierarchical Bayesian model which overcomes sparsity, sharing information across cells genomic features to robustly genuine biological heterogeneity. identify highly variable that drive epigenetic heterogeneity, perform differential variability analyses. We illustrate how...
Abstract Technological advances have enabled the joint analysis of multiple molecular layers at single cell resolution. At same time, increased experimental throughput has facilitated study larger numbers conditions. While methods for analysing single-cell data that model resulting structure either these dimensions are beginning to emerge, current do not account complex designs include both views (modalities or assays) and groups (conditions experiments). Here we present Multi-Omics Factor...
Summary During mouse gastrulation, extraembryonic mesoderm (ExEM) contributes to the yolk sac (YS) and allantois, both of which are essential for successful gestation. Although genetic networks coordinating intra-embryonic mesodermal subtype specification well-studied, mechanisms driving ExEM diversification poorly understood. Here, we reveal that embryoid body in vitro differentiation generates two distinct lineages cells matching YS allantois respectively. Combining models with vivo...
Abstract Early organogenesis represents a key step in animal development, where pluripotent cells divide and diversify to initiate formation of all major organs. Here, we used scRNA-Seq profile over 300,000 single cell transcriptomes sampled 6 hour intervals from mouse embryos between E8.5 E9.5. Combining this dataset with our previous E6.5 atlas resulted densely time course 400,000 early gastrulation organogenesis. Computational lineage reconstruction at full organismal scale identified...
Abstract Parallel single-cell sequencing protocols represent powerful methods for investigating regulatory relationships, including epigenome-transcriptome interactions. Here, we report a novel method parallel chromatin accessibility, DNA methylation and transcriptome profiling. scNMT-seq (single-cell nucleosome, transcription sequencing) uses GpC methyltransferase to label open followed by bisulfite RNA sequencing. We validate applying it differentiating mouse embryonic stem cells, finding...
Abstract Multi-omic studies promise the improved characterization of biological processes across molecular layers. However, methods for unsupervised integration resulting heterogeneous datasets are lacking. We present Multi-Omics Factor Analysis (MOFA), a computational method discovering principal sources variation in multi-omic datasets. MOFA infers set (hidden) factors that capture and technical variability. It disentangles axes heterogeneity shared multiple modalities those specific to...
Abstract Factor analysis is among the most-widely used methods for dimensionality reduction in genome biology, with applications from personalized health to single-cell studies. Existing implementations of factor assume independence observed samples, an assumption that fails emerging spatio-temporal profiling Here, we present MEFISTO, a flexible and versatile toolbox modelling high-dimensional data when spatial or temporal dependencies between samples are known. MEFISTO maintains established...
Abstract Formation of the three primary germ layers during gastrulation is an essential step in establishment vertebrate body plan. Recent studies employing single cell RNA-sequencing have identified major transcriptional changes associated with layer specification. Global epigenetic reprogramming accompanies these changes, but role epigenome regulating early fate choice remains unresolved, and coordination between different unclear. Here we describe first triple-omics map chromatin...
The majority of high-throughput single-cell molecular profiling methods quantify RNA expression; however, recent multimodal add simultaneous measurement genomic, proteomic, epigenetic, and/or spatial information on the same cells. development new statistical and computational in Bioconductor for such data will be facilitated by easy availability landmark datasets using standard classes.