Sunday, June 16, 2024

Re: Abstract Required | From Genetic Discoveries to Gene Function in Human Diseases Conference, 13 - 16 July 2024, Portugal

Title: Single-cell genomics and regulatory networks for 388 human brains

Speaker: Mark Gerstein

Abstract:

Single-cell genomics is a powerful tool for studying heterogeneous
tissues such as the brain. Yet little is understood about how genetic
variants influence cell-level gene expression. Addressing this, we
uniformly processed single-nuclei, multiomics datasets into a resource
comprising >2.8 million nuclei from the prefrontal cortex across 388
individuals with various brain-related disorders and controls. For 28
harmonized neuronal and non-neuronal cell types, we assessed
population-level variation in expression and chromatin across gene
families and drug targets. Integration of expression and genotype data
revealed >1.4 million single-cell expression quantitative trait loci
(eQTLs), many of which were not seen in bulk gene-expression datasets.
The chromatin datasets allowed for the identification of >550,000
single-cell cis-regulatory elements enriched at loci linked to
brain-related traits. Combining expression, chromatin, and eQTL
datasets, we built cell type–specific gene regulatory and cell-to-cell
communication networks, which manifest cellular changes in aging and
neuropsychiatric disorders, including altered Wnt signaling in
schizophrenia and bipolar disorder. We further constructed an
integrative deep-learning model that accurately imputes single-cell
expression and simulates perturbations. The model prioritized ~250
disease-risk genes and drug targets with associated cell types,
suggesting potential precision-medicine approaches for
neuropsychiatric disorders.

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i0lis24, eur24


On Wed, Jun 12, 2024 at 5:41 AM Rosie Johnson
<Rosie@fusion-conferences.com> wrote:
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> Dear Speakers,
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> Please submit your abstract for the 'From Genetic Discoveries to Gene Function in Human Diseases' conference by Friday 21st June 2024 for inclusion in the conference abstract book.
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