Toward universal cell embeddings: integrating single-cell RNA-seq datasets across species with SATURN.

Analysis of single-cell datasets generated from diverse organisms offers unprecedented opportunities to unravel fundamental evolutionary processes of conservation and diversification of cell types. However, interspecies genomic differences limit the joint analysis of cross-species datasets to homologous genes. Here we present SATURN, a deep learning method for learning universal cell embeddings that encodes genes' biological properties using protein language models. By coupling protein embeddings from language models with RNA expression, SATURN integrates datasets profiled from different species regardless of their genomic similarity. SATURN can detect functionally related genes coexpressed across species, redefining differential expression for cross-species analysis. Applying SATURN to three species whole-organism atlases and frog and zebrafish embryogenesis datasets, we show that SATURN can effectively transfer annotations across species, even when they are evolutionarily remote. We also demonstrate that SATURN can be used to find potentially divergent gene functions between glaucoma-associated genes in humans and four other species.

Enhanced Point-of-Care Ultrasound Applications by Integrating Automated Feature-Learning Systems Using Deep Learning.

Recent applications of artificial intelligence (AI) and deep learning (DL) in health care include enhanced diagnostic imaging modalities to support clinical decisions and improve patients' outcomes. Focused on using automated DL-based systems to improve point-of-care ultrasound (POCUS), we look at DL-based automation as a key field in expanding and improving POCUS applications in various clinical settings. A promising additional value would be the ability to automate training model selections for teaching POCUS to medical trainees and novice sonologists. The diversity of POCUS applications and ultrasound equipment, each requiring specialized AI models and domain expertise, limits the use of DL as a generic solution. In this article, we highlight the most advanced potential applications of AI in POCUS tailored to high-yield models in automated image interpretations, with the premise of improving the accuracy and efficacy of POCUS scans.

Predicting transcriptional outcomes of novel multigene perturbations with GEARS.

Understanding cellular responses to genetic perturbation is central to numerous biomedical applications, from identifying genetic interactions involved in cancer to developing methods for regenerative medicine. However, the combinatorial explosion in the number of possible multigene perturbations severely limits experimental interrogation. Here, we present graph-enhanced gene activation and repression simulator (GEARS), a method that integrates deep learning with a knowledge graph of gene-gene relationships to predict transcriptional responses to both single and multigene perturbations using single-cell RNA-sequencing data from perturbational screens. GEARS is able to predict outcomes of perturbing combinations consisting of genes that were never experimentally perturbed. GEARS exhibited 40% higher precision than existing approaches in predicting four distinct genetic interaction subtypes in a combinatorial perturbation screen and identified the strongest interactions twice as well as prior approaches. Overall, GEARS can predict phenotypically distinct effects of multigene perturbations and thus guide the design of perturbational experiments.

Towards Universal Cell Embeddings: Integrating Single-cell RNA-seq Datasets across Species with SATURN.

Analysis of single-cell datasets generated from diverse organisms offers unprecedented opportunities to unravel fundamental evolutionary processes of conservation and diversification of cell types. However, inter-species genomic differences limit the joint analysis of cross-species datasets to homologous genes. Here, we present SATURN, a deep learning method for learning universal cell embeddings that encodes genes' biological properties using protein language models. By coupling protein embeddings from language models with RNA expression, SATURN integrates datasets profiled from different species regardless of their genomic similarity. SATURN has a unique ability to detect functionally related genes co-expressed across species, redefining differential expression for cross-species analysis. We apply SATURN to three species whole-organism atlases and frog and zebrafish embryogenesis datasets. We show that cell embeddings learnt in SATURN can be effectively used to transfer annotations across species and identify both homologous and species-specific cell types, even across evolutionarily remote species. Finally, we use SATURN to reannotate the five species Cell Atlas of Human Trabecular Meshwork and Aqueous Outflow Structures and find evidence of potentially divergent functions between glaucoma associated genes in humans and other species.