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Reduced gene templates for supervised analysis of scale-limited CRISPR-Cas9 fitness screens

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Description

Many analytical tasks performed on data from genome-wide CRISPR-Cas9 screens are either optionally or necessarily performed in a supervised manner. In this scenario, the screening outcomes observed for large sets of positive/negative controls, i.e. genes that are prior known to be essential/nonessential for cell survival, are adopted as benchmark or template classifiers. The analytical tasks accomplished by supervised methods range from quality control [1-5], to fold-change scaling for inter-screen comparisons and interpretability [6-11], to calling statistical significant essential genes [1,9,11-14].
However, the size of positive/negative control genes has a significant impact on the scale of the experiment to perform and it proves quite prohibitive for scale-limiteds CRISPR-Cas9 screens (e.g, CRISPR-Cas9 screens using focused libraries, primary cultures, organoids or patient-derived xenografts), where the number of reference genes would become comparable or even larger than that of the genes under investigation.
Minimal Template Estimator (MinTEs) [15] is a computational framework for assembling gene templates of reduced size allowing supervised analyses of data from scale-limited CRISPR-Cas9 screens, while having a limited, user-defined impact on the overall library size. MinTEs is trained on two large genome-wide pooled CRISPR-Cas9 datasets from Project Score [16] and Project Achilles [10], respectively.
This repository contains the snakemake pipeline to derive reduced gene templates from [15]. Zenodo DOI DOI.

Setup

Clone code repository and install dependencies:

git clone https://github.com/AleVin1995/MinTEs.git

cd MinTEs

conda env create -f envs/MinTEs.yaml

Furthermore, figures are reproducible via Jupyter notebooks (available in the notebooks subfolder) and also executable via browser Open In Colab

References

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[2] Gonçalves, E., Thomas, M., Behan, F.M., Picco, G., Pacini, C., Allen, F., Vinceti, A., Sharma, M., Jackson, D.A., Price, S., et al. (2021). Minimal genome-wide human CRISPR-Cas9 library. Genome Biol. 22, 40.

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[10] Meyers, R.M., Bryan, J.G., McFarland, J.M., Weir, B.A., Sizemore, A.E., Xu, H., Dharia, N.V., Montgomery, P.G., Cowley, G.S., Pantel, S., et al. (2017). Computational correction of copy number effect improves specificity of CRISPR-Cas9 essentiality screens in cancer cells. Nat. Genet. 49, 1779–1784.

[11] Pacini, C., Dempster, J.M., Boyle, I., Gonçalves, E., Najgebauer, H., Karakoc, E., van der Meer, D., Barthorpe, A., Lightfoot, H., Jaaks, P., et al. (2021). Integrated cross-study datasets of genetic dependencies in cancer. Nat. Commun. 12, 1661.

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[14] Hart, T., Chandrashekhar, M., Aregger, M., Steinhart, Z., Brown, K.R., and MacLeod, G. (2015). High-resolution CRISPR screens reveal fitness genes and genotype-specific cancer liabilities. Cell 163.

[15] Vinceti, Alessandro, Umberto Perron, Lucia Trastulla, and Francesco Iorio. 2022. “Reduced Gene Templates for Supervised Analysis of Scale-Limited CRISPR-Cas9 Fitness Screens.” bioRxiv. https://doi.org/10.1101/2022.02.28.482271.

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