Leonardo Collado‐Torres
A5075979341- Single-cell and spatial transcriptomics
- Molecular Biology Techniques and Applications
- RNA modifications and cancer
- RNA Research and Splicing
- Gene expression and cancer classification
- Epigenetics and DNA Methylation
- Genetic Associations and Epidemiology
- Cancer-related molecular mechanisms research
- Bioinformatics and Genomic Networks
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- Genetics and Neurodevelopmental Disorders
- Genetic Syndromes and Imprinting
- Cell Image Analysis Techniques
- Tryptophan and brain disorders
- Genomics and Chromatin Dynamics
- Neurogenesis and neuroplasticity mechanisms
- Diet and metabolism studies
- Mycobacterium research and diagnosis
- CRISPR and Genetic Engineering
- Identity, Memory, and Therapy
- MicroRNA in disease regulation
- Neuroscience and Neuropharmacology Research
- Gene Regulatory Network Analysis
Johns Hopkins University
2016-2025
Lieber Institute for Brain Development
2016-2025
Bloomberg (United States)
2024
Johns Hopkins Medicine
2014-2023
University of Bari Aldo Moro
2022
Discovery Institute
2020
Harvard University
2011
Universidad Nacional Autónoma de México
2010
Most genetic risk for psychiatric disease lies in regulatory regions, implicating pathogenic dysregulation of gene expression and splicing. However, comprehensive assessments transcriptomic organization diseased brains are limited. In this work, we integrated genotypes RNA sequencing brain samples from 1695 individuals with autism spectrum disorder (ASD), schizophrenia, bipolar disorder, as well controls. More than 25% the transcriptome exhibits differential splicing or expression,...
Despite progress in defining genetic risk for psychiatric disorders, their molecular mechanisms remain elusive. Addressing this, the PsychENCODE Consortium has generated a comprehensive online resource adult brain across 1866 individuals. The contains ~79,000 brain-active enhancers, sets of Hi-C linkages, and topologically associating domains; single-cell expression profiles many cell types; quantitative-trait loci (QTLs); further QTLs associated with chromatin, splicing, cell-type...
RegulonDB ( http://regulondb.ccg.unam.mx/ ) is the primary reference database of best-known regulatory network any free-living organism, that Escherichia coli K-12. The major conceptual change since 3 years ago an expanded biological context so transcriptional regulation now part a unit initiates with signal and continues transduction to core regulation, modifying expression affected target genes responsible for response. We call these genetic sensory response units, or Gensor Units. have...
Genes implicated in neuropsychiatric disorders are active human fetal brain, yet difficult to study a longitudinal fashion. We demonstrate that organoids from pluripotent cells model cerebral cortical development on the molecular level before 16 weeks postconception. A multiomics analysis revealed differentially genes and enhancers, with greatest changes occurring at transition stem progenitors. Networks of converging gene enhancer modules were assembled into six four global patterns...
We present recount3, a resource consisting of over 750,000 publicly available human and mouse RNA sequencing (RNA-seq) samples uniformly processed by our new Monorail analysis pipeline. To facilitate access to the data, we provide recount3 snapcount R/Bioconductor packages as well complementary web resources. Using these tools, data can be downloaded study-level summaries or queried for specific exon-exon junctions, genes, samples, other features. used process local and/or private allowing...
Abstract Background Spatially-resolved transcriptomics has now enabled the quantification of high-throughput and transcriptome-wide gene expression in intact tissue while also retaining spatial coordinates. Incorporating precise mapping activity advances our understanding tissue-specific biological processes. In order to interpret these novel data types, interactive visualization tools are necessary. Results We describe spatialLIBD , an R/Bioconductor package interactively explore...
SpatialExperiment is a new data infrastructure for storing and accessing spatially-resolved transcriptomics data, implemented within the R/Bioconductor framework, which provides advantages of modularity, interoperability, standardized operations comprehensive documentation. Here, we demonstrate structure user interface with examples from 10x Genomics Visium seqFISH platforms, provide access to example datasets visualization tools in STexampleData, TENxVisiumData ggspavis packages.
Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet little understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multiomics datasets into resource comprising >2.8 million nuclei from prefrontal cortex across 388 individuals. For 28 cell types, assessed population-level variation in expression and chromatin families drug targets. We identified >550,000 type-specific...
The complexity and heterogeneity of schizophrenia have hindered mechanistic elucidation the development more effective therapies. Here, we performed single-cell dissection schizophrenia-associated transcriptomic changes in human prefrontal cortex across 140 individuals two independent cohorts. Excitatory neurons were most affected cell group, with transcriptional converging on neurodevelopment synapse-related molecular pathways. Transcriptional alterations included known genetic risk...
Nucleotide changes in gene regulatory elements are important determinants of neuronal development and diseases. Using massively parallel reporter assays primary human cells from mid-gestation cortex cerebral organoids, we interrogated the cis-regulatory activity 102,767 open chromatin regions, including thousands sequences with cell type-specific accessibility variants associated brain regulation. In cells, identified 46,802 active enhancer 164 that alter activity. Activity was comparable...
The molecular pathology of stress-related disorders remains elusive. Our brain multiregion, multiomic study posttraumatic stress disorder (PTSD) and major depressive (MDD) included the central nucleus amygdala, hippocampal dentate gyrus, medial prefrontal cortex (mPFC). Genes exons within mPFC carried most disease signals replicated across two independent cohorts. Pathways pointed to immune function, neuronal synaptic regulation, hormones. Multiomic factor gene network analyses provided...
The molecular organization of the human neocortex historically has been studied in context its histological layers. However, emerging spatial transcriptomic technologies have enabled unbiased identification transcriptionally defined domains that move beyond classic cytoarchitecture. We used Visium gene expression platform to generate a data-driven neuroanatomical atlas across anterior-posterior axis dorsolateral prefrontal cortex. Integration with paired single-nucleus RNA-sequencing data...
Neuropsychiatric genome-wide association studies (GWASs), including those for autism spectrum disorder and schizophrenia, show strong enrichment regulatory elements in the developing brain. However, prioritizing risk genes mechanisms is challenging without a unified atlas. Across 672 diverse human brains, we identified 15,752 harboring gene, isoform, and/or splicing quantitative trait loci, mapping 3739 to cellular contexts. Gene expression heritability drops during development, likely...
Abstract Human induced pluripotent stem cells (hiPSCs) are a powerful model of neural differentiation and maturation. We present hiPSC transcriptomics resource on corticogenesis from 5 iPSC donor 13 subclonal lines across 9 time points over broad conditions: self-renewal, early neuronal differentiation, precursor (NPCs), assembled rosettes, differentiated cells. identify widespread changes in the expression both individual features global patterns transcription. next demonstrate that...
Gene annotations, such as those in GENCODE, are derived primarily from alignments of spliced cDNA sequences and protein sequences. The impact RNA-seq data on annotation has been confined to major projects like ENCODE Illumina Body Map 2.0.We aligned 21,504 Illumina-sequenced human samples the Sequence Read Archive (SRA) genome compared detected exon-exon junctions with several recent gene annotations. We found 56,861 (18.6%) at least 1000 that were not annotated, their expression associated...
Cellular heterogeneity in the human brain obscures identification of robust cellular regulatory networks, which is necessary to understand function non-coding elements and impact genetic variation. Here we integrate genome-wide chromosome conformation data from purified neurons glia with transcriptomic enhancer profiles, characterize gene landscape two major cell classes brain. We then leverage cell-type-specific landscapes gain insight into etiology several disorders. find that Alzheimer's...