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In the rapidly evolving field of Methods in Computational Genomics this editorial series illuminates the forefront of experimental techniques and methodologies. From dissecting large multidimensional numeric datasets to predicting the functions of novel genomic entities, these approaches have revolutionized our understanding of genomic data. This editorial underscores two pivotal themes: the development of innovative tools and software, and the integration of artificial intelligence (AI) and machine learning in genomic research. These themes exemplify the significant impact computational methods have had on genomics, providing novel insights into complex biological questions. As we delve into each theme, we witness the transformative role of computational genomics in addressing contemporary challenges in biological research, marking a new era of discovery and innovation in the field.