Gort-Freitas, N. A. | bioRxiv Science

bioRxiv2026

Temporal Biodynamics: An AI Platform for Identification of Stage-Relevant Targets and Biomarkers

Temporal modeling of disease progression is poised to revolutionize the process of target identification, leading to better characterization of and intervention at the critical early stages of chronic conditions. Temporal Biodynamics is an artificial intelligence-driven platform that leverages within-tissue heterogeneity in cross-sectional cohorts to assemble a single, continuous trajectory of transcriptomic changes between health and disease. We demonstrate that the platform enriches for known disease-associated genes and proteins by more than 50% over the conventional case-control comparisons. When compared to other published pseudotime methods, our models were better at extracting disease-relevant signals in the presence of confounders and co-morbidities. The Temporal Biodynamics platform enables rich profiling of a disease continuum, providing temporal insights that are otherwise hidden by the traditional discrete staging of chronic diseases. This includes detecting cascades of molecular events, providing clues regarding causality, and increasing confidence in blood-based protein biomarkers using tissue-based context.

bioinformatics↗

bioRxiv2025

Immune cell type divergence in a basal chordate

Evolutionary adaptations often occur at the level of cell types and cellular function. Innate immune cells are a promising system for studying cell type evolution, as they are widespread across metazoans, have several conserved functions, and are under selective pressure from pathogens. However, molecular characterizations of invertebrate immune cells are limited, and it remains unclear whether invertebrate immune cell types are homologous to those in vertebrates. Here we use single-cell RNA sequencing, in situ hybridization, and live reporters to define the identity of blood cell states from a basal chordate, Ciona robusta. We find evidence that C. robusta circulating blood contains a differentiation hierarchy that gives rise to at least eight major morphotypes, constituting approximately half of mature blood cell states. The mature cell states include phagocytes, as well as cells variously expressing vanadium-binding proteins, carbonic anhydrases, pattern recognition receptors, cytokines, and complement factors. Despite the expression of homologs to vertebrate immune components, extensive divergence between tunicate and vertebrate immune cells obscures cell state homology. Altogether, this work modernizes blood cell classifications in C. robusta and extends the known repertoire of immune cells within chordates.

evolutionary biology↗