Computational strategies for cross-species knowledge transfer

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 use transcriptome data and/or molecular networks. Our Perspective addresses four key areas: (1) transferring disease and gene annotation knowledge across species, (2) identifying functionally equivalent molecular components, (3) inferring equivalent perturbed genes or gene sets and (4) identifying equivalent cell types. We conclude with an outlook on future directions and several key challenges that remain in cross-species knowledge transfer, including introducing the concept of 'agnology' to describe functional equivalence of biological entities, regardless of their evolutionary origins. This concept is becoming pervasive in integrative data-driven models in which evolutionary origins of functions can remain unresolved.