Andrew Chess
- Olfactory and Sensory Function Studies
- Epigenetics and DNA Methylation
- Neurobiology and Insect Physiology Research
- Biochemical Analysis and Sensing Techniques
- Genomic variations and chromosomal abnormalities
- Genetic Associations and Epidemiology
- Genetic Syndromes and Imprinting
- Genomics and Chromatin Dynamics
- Genomics and Rare Diseases
- RNA Research and Splicing
- Cancer Genomics and Diagnostics
- Bioinformatics and Genomic Networks
- Single-cell and spatial transcriptomics
- Genetics and Neurodevelopmental Disorders
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- RNA modifications and cancer
- RNA regulation and disease
- Genomics and Phylogenetic Studies
- T-cell and B-cell Immunology
- CRISPR and Genetic Engineering
- Tryptophan and brain disorders
- RNA and protein synthesis mechanisms
- Gut microbiota and health
- Axon Guidance and Neuronal Signaling
- Immune Cell Function and Interaction
Allen Institute for Brain Science
2014-2024
Icahn School of Medicine at Mount Sinai
2015-2024
Johns Hopkins University
2024
Johns Hopkins Medicine
2024
Lieber Institute for Brain Development
2024
C4 Therapeutics (United States)
2024
Yale University
2024
Genomics (United Kingdom)
2022
Center for Information Technology
2020
Pediatrics and Genetics
2020
Abstract Background Noncoding RNA species play a diverse set of roles in the eukaryotic cell. While much recent attention has focused on smaller species, larger noncoding transcripts are also thought to be highly abundant mammalian cells. To search for large RNAs that might control gene expression or mRNA metabolism, we used Affymetrix arrays identify polyadenylated displaying nuclear enrichment. Results This screen identified no more than three transcripts; XIST , and two unique enriched (...
Differential DNA methylation is important for the epigenetic regulation of gene expression. Allele-specific inactive X chromosome has been demonstrated at promoter CpG islands, but overall pattern on active X(Xa) and (Xi) chromosomes unknown. We performed allele-specific analysis more than 1000 informative loci along human chromosome. The Xa displays two times as much Xi. This concentrated bodies, affecting multiple neighboring CpGs. Before inactivation, all these body–methylated sites are...
Monoallelic expression with random choice between the maternal and paternal alleles defines an unusual class of genes comprising X-inactivated a few autosomal gene families. Using genome-wide approach, we assessed allele-specific transcription about 4000 human in clonal cell lines found that more than 300 were subject to monoallelic expression. For majority genes, also observed some displaying biallelic Clonal reflect independent express maternal, paternal, or both for each these genes. This...
Abstract The availability of high-quality RNA-sequencing and genotyping data post-mortem brain collections from consortia such as CommonMind Consortium (CMC) the Accelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD) enable generation a large-scale cis- eQTL meta-analysis. Here we generate cerebral cortical 1433 samples available four cohorts (identifying >4.1 million significant >18,000 genes), well cerebellar 261 874,836 >10,000 genes). We find substantially improved...
Abstract Schizophrenia and bipolar disorder are serious mental illnesses that affect more than 2% of adults. While large-scale genetics studies have identified genomic regions associated with disease risk, less is known about the molecular mechanisms by which risk alleles small effects lead to schizophrenia disorder. In order fill this gap between phenotype, we undertaken a multi-cohort genomics study postmortem brains from controls, individuals Here present public resource functional data...
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 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...