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https://github.com/gersteinlab/psychencode_singlecell_integrative

Integrative Analyses across 388 human brain samples at single-cell resolution
https://github.com/gersteinlab/psychencode_singlecell_integrative

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Integrative Analyses across 388 human brain samples at single-cell resolution

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# PsychENCODE Single-cell Integrative Analysis
This repository contains the code generated as part of the PsychENCODE consortium's [Integrative Analysis paper](https://doi.org/10.1101/2024.03.18.585576).

## Overview
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, multi-omics datasets into a resource comprising >2.8M nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550K cell-type-specific regulatory elements and >1.4M single-cell expression-quantitative-trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest cellular changes in aging and neuropsychiatric disorders. We further constructed an integrative model accurately imputing single-cell expression and simulating perturbations; the model prioritized ~250 disease-risk genes and drug targets with associated cell types.

For a comprehensive understanding, the publication provides detailed insights into our methodologies, results, and discussions. We recommend reading the paper alongside exploring this repository.

## Publication

- **Title**: Single-cell genomics & regulatory networks for 388 human brains
- **Link**: [Biorxiv preprint](https://doi.org/10.1101/2024.03.18.585576)

## Key Highlights

- **Extensive Dataset**: More than 2.8 million nuclei from the prefrontal cortex across 388 individuals.
- **Cell-Type Specific Regulatory Elements**: Identification of over 550K unique regulatory elements.
- **Single-Cell eQTLs Exploration**: Unearthed more than 1.4 million eQTLs offering insights into cell-type regulatory networks and inter-cellular communication.
- **Aging and Neuropsychiatric Disorders**: Comprehensive network models highlighting expression changes associated with aging and various neuropsychiatric disorders.
- **Integrative Model Construction**: A model that accurately imputes cell-type gene expression, prioritizing potential disease-risk genes and drug targets, associating them with specific cell types.