Multi-objective two-archive evolutionary algorithm to optimize the discovery of gene networks involved in cancer survival

Gene networks have gained considerable relevance in cancer research, enabling the representation of complex biological relationships that provide insights into the mechanisms driving tumor development and progression. The increasing availability of biological data facilitates the construction of clinically relevant gene networks by integrating multiple information sources. Specifically, we consider mutation data, patient survival data, and protein-protein interaction data to identify networks whose genes are recurrently mutated, significantly involved in patient survival, and functionally associated. To this end, we apply multi-objective optimization to simultaneously maximize survival impact, functional association, and mutation coverage. Herein, we introduce MOTEA-GENSU (Multi-Objective Two-archive Evolutionary Algorithm to discover GEne Networks involved in SUrvival), a novel method that employs two collaborative archives and intelligent evolutionary operators to guide the generation of high-quality gene networks. Evaluation across 27 real biological scenarios covering diverse cancer types shows that MOTEA-GENSU outperforms existing methods, achieving superior results in 92.6% of comparisons, with improvements of up to 315.8% over the best-performing competing approach, and consistently surpassing all state-of-the-art methods on average within each evaluated dataset. Biological analysis of the identified networks validates their functional coherence and significant impact on cancer patient survival, revealing clinically relevant networks composed of genes with demonstrated prognostic value.