MALTA: a calculator for estimating the coverage with shRNA, CRISPR, and cDNA libraries

Area of Science:

• Genetics
• Molecular Biology
• Bioinformatics

Background:

• Genetic screens using pooled libraries (shRNA, CRISPR, cDNA) require efficient library transfer into recipient cells.
• Varied element abundance within libraries complicates accurate representation in downstream assays.
• Reproducing the starting library population is crucial for comparing genetic screen outcomes.

Purpose of the Study:

• To develop a computational tool for determining the minimum number of recipient cells required for adequate sampling of pooled genetic libraries.
• To enable users to specify desired probability levels for full library element representation.
• To facilitate accurate comparisons between different genetic screening experiments.

Main Methods:

• The application accepts a list of library elements and their respective abundances.
• It calculates the minimum sampling number based on user-defined probability thresholds.
• Utilizes Monte Carlo simulations to empirically determine element distribution based on user-specified parameters.

Main Results:

• The tool provides a calculated minimum cell number to ensure comprehensive library representation.
• Users can adjust parameters like subpopulation focus for tailored calculations.
• Empirical distributions of library elements are generated through simulations.

Conclusions:

• This application simplifies the critical step of determining adequate cell numbers for genetic screens.
• It enhances the reliability and comparability of results from shRNA, CRISPR, and cDNA library screens.
• Accurate library sampling is essential for robust genetic discovery and analysis.