Integrative bioinformatics approaches reveal key hub genes in cyanobacteria: insights from Synechocystis sp. PCC 6803 and Geminocystis sp. NIES-3708 under abiotic stress conditions: insights from Synechocystis sp. PCC 6803 and Geminocystis sp. NIES-3708 under abiotic stress conditions

Background: Cyanobacteria, particularly Synechocystis sp. PCC 6803, serve as model organisms for studying acclimation strategies that enable adaptation to various environmental stresses. Understanding the molecular mechanisms underlying these adaptations provides insight into how cells adjust gene expression in response to challenging conditions. Objective: To analyze the transcriptome data of Synechocystis sp. PCC 6803 under light, salinity, and iron stress conditions and to identify hub genes potentially involved in stress response, specifically comparing the findings with Geminocystis sp. NIES-3708. Methods: A comprehensive bioinformatics approach was applied, integrating meta-analysis, weighted gene co-expression network analysis (WGCNA), and a Random Forest (RF) machine learning algorithm. These approaches underscore the robustness of our findings, allowing for a more nuanced understanding of gene interactions and their functional relevance in stress responses. This methodology was used to identify key hub genes in Synechocystis sp. PCC 6803 that may have conserved roles in Geminocystis sp. NIES-3708. A total of four potential hub genes, including slr1392, slr1484, sll1549, and sll1863, were identified. Among these, only sll1549 had a homolog (GM3708_2556) with 71% sequence similarity and 70% query coverage in Geminocystis sp. NIES-3708. The expression of GM3708_2556 was further evaluated under nitrate, salt, and combined salinity-nitrate stress conditions using RT-qPCR. Results: Transcript levels of GM3708_2556 increased significantly under salt stress (3.35-fold, p-value < 0.05) and combined salinity-nitrate stress (2.24-fold, p-value < 0.05) compared to control conditions, while no significant change was observed under nitrate stress alone. These results suggest that GM3708_2556 may play a crucial role in the organism’s response to salt stress, with potential interactions in nitrate metabolism. Conclusion: This study highlights the gene GM3708_2556 as a significant factor in salt stress response, with implications for conserved functional roles across cyanobacterial species. Furthermore, the findings have potential relevance to biotechnology, particularly in engineering stress-resistant cyanobacterial strains for applications in sustainable agriculture and bioenergy production.