Project background

Project background

Aims

Our aims are as follows (taken from the FGx website).

"This research cluster will tackle the “missing link” between the genome and disease. Our aim is to identify molecules in our bodies that cause disease by looking at how tiny variations in the genome change these molecules in single cells. We will create a unique dataset by reading molecular signals in human cells donated by hundreds of patients, potentially leading to ideas for new, effective drugs. ... In the Molecular Mechanisms Cluster we hold ourselves to a simple measure of success: the number of disease genes explained (number of disease-associated common genetic variants significantly colocalising with molecular quantitative trait loci)."

The goals are:
⭐️ Identify QTLs
⭐️ Create open source database of QTLs
⭐️ Colocalise QTLs

The team:

Max Pickup, Katie Hildersley, Natasha Palmalux, Silvia Shen: Post-doctoral research fellows
Kathryn Campbell, Dominique McCormick: ODAP/HPC team
Wilna Oosthuyzen: Programme manager
Konrad Rawlik, Kenneth Baillie: MMC principle investigators

Computational plans:

Main priority

1. Standard single cell pipeline using Parse bioinformatics tooling (FastQ -> count matrices -> H5AD + html reports)

FastQ/BCL level

2. Custom single cell pipeline (ARCAS) (Kallisto-based mapping)
3. Non-standard quantification: isoform quantification, poly-A site calling
4. Sample multiplexing assessment
5. Cell number and read depth evaluation

Count matrix level

6. Cell typing
7. Sample integration
8. Differential gene expression across perturbations