# Whole-Exome Sequencing (WES) Analysis

This repository contains the files and scripts used for the WES analysis presented in:

**Conti et al., 2025**  
*Senescence and inflammation are unintended adverse consequences of CRISPR-Cas9/AAV6 mediated gene editing in hematopoietic stem cells*.  
Published in **Cell Reports Medicine**.

## 🔬 Study Context

Whole-exome sequencing (WES) was performed to evaluate potential genomic alterations introduced by CRISPR-Cas9/AAV6 editing in human hematopoietic stem and progenitor cells (HSPCs). The analysis focused on variant detection, comparison across experimental conditions, and functional annotation.

## 📂 Repository Content

- `Variants/`  
  Contains filtered variant call files (VCFs) and summary tables per sample or condition.

- `callable_nt/`  
  BED files reporting callable nucleotide regions across samples, used to control for coverage and false negatives.

- `genePanels/`  
  Gene sets used for annotation and targeted analysis (e.g. DDR genes, myeloid panels).

- `Plot.R`  
  R script used to generate summary plots included in the manuscript. It includes variant counts, overlaps, and gene-level summaries.

## 📊 Data Availability

WES data supporting this analysis are available via the Gene Expression Omnibus (GEO), under the SuperSeries accession **[GSE244257](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE244257)**.

## 🧰 Tools and Notes

- Variant calling was performed using GATK best practices.
- Callable regions were computed to normalize comparisons across samples.
- Variant annotation was carried out using Ensembl VEP and custom gene panels.

## 📌 Citation

If you use this repository or data, please cite:

> Conti A., Giannetti K., Midena F., et al. (2025).  
> *Senescence and inflammation are unintended adverse consequences of CRISPR-Cas9/AAV6 mediated gene editing in hematopoietic stem cells*.  
> **Cell Reports Medicine**.  
> GEO accession: GSE244257