Multi-knockout genetic network analysis: the Rad6 example.

A novel and rigorous Multi-perturbation Shapley Value Analysis (MSA) method has been recently presented [12]. The method addresses the challenge of defining and calculating the functional causal contributions of elements of a biological system. This paper presents the first study applying MSA to the analysis of gene knockout data. The MSA identifies the importance of genes in the Rad6 DNA repair pathway of the yeast S. cerevisiae, quantifying their contributions and characterizing their functional interactions. Incorporating additional biological knowledge, a new functional description of the Rad6 pathway is provided, predicting the existence of additional DNA polymerase and RFC-like complexes. The MSA is the first method for rigorously analyzing multi-knockout experiments, which are likely to soon become a standard and necessary tool for analyzing complex biological systems.