Rosen Yanay, Brbić Maria, Roohani Yusuf, Swanson Kyle, Li Ziang, Leskovec Jure
Department of Computer Science, Stanford University, Stanford, CA, USA.
School of Computer and Communication Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
Nat Methods. 2024 Aug;21(8):1492-1500. doi: 10.1038/s41592-024-02191-z. Epub 2024 Feb 16.
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.
对来自不同生物体的单细胞数据集进行分析,为揭示细胞类型保守和多样化的基本进化过程提供了前所未有的机会。然而,种间基因组差异限制了跨物种数据集对同源基因的联合分析。在此,我们展示了SATURN,这是一种深度学习方法,用于学习通用细胞嵌入,它使用蛋白质语言模型对基因的生物学特性进行编码。通过将语言模型中的蛋白质嵌入与RNA表达相结合,SATURN整合了来自不同物种的数据集,而不管它们的基因组相似性如何。SATURN可以检测跨物种共表达的功能相关基因,重新定义用于跨物种分析的差异表达。将SATURN应用于三个物种的全生物体图谱以及青蛙和斑马鱼胚胎发育数据集,我们表明SATURN可以有效地跨物种转移注释,即使它们在进化上相距甚远。我们还证明,SATURN可用于发现人类青光眼相关基因与其他四个物种之间潜在的不同基因功能。