Computational strategies for cross-species knowledge transfer and translational biomedicine

Research organisms provide invaluable insights into human biology and diseases, serving as essential tools for functional experiments, disease modeling, and drug testing. However, evolutionary divergence between humans and research organisms hinders effective knowledge transfer across species. Here, we review state-of-the-art methods for computationally transferring knowledge across species, primarily focusing on methods that utilize transcriptome data and/or molecular networks. We introduce the term "agnology" to describe the functional equivalence of molecular components regardless of evolutionary origin, as this concept is becoming pervasive in integrative data-driven models where the role of evolutionary origin can become unclear. Our review addresses four key areas of information and knowledge transfer across species: (1) transferring disease and gene annotation knowledge, (2) identifying agnologous molecular components, (3) inferring equivalent perturbed genes or gene sets, and (4) identifying agnologous cell types. We conclude with an outlook on future directions and several key challenges that remain in cross-species knowledge transfer.