arXivDaily arXiv每日学术速递 周一至周五更新
北美退伍军人节(Veterans Day),12 日无更新
arXiv 2106.02246cs.LGq-bio.MNq-bio.QMq-bio.TO
收藏

蛋白质网络的深度上下文学习器

Deep Contextual Learners for Protein Networks

Harvard University(哈佛大学);Broad Institute of MIT and Harvard(麻省理工学院和哈佛大学博德研究所);Harvard Data Science(哈佛数据科学研究院)

Michelle M. Li, Marinka Zitnik

摘要:

空间背景是理解健康和疾病的核心。然而,参考蛋白质相互作用网络缺乏这种情境化,从而限制了蛋白质相互作用可能在人体中发生的位置以及它们在疾病中如何改变的研究。情境化的蛋白质相互作用可以更好地表征具有疾病特异性相互作用的基因,并阐明疾病在特定细胞类型中的表现。在这里,我们介绍AWARE,一种将细胞和组织背景注入蛋白质嵌入的图形神经消息传递方法。AWARE优化了多尺度嵌入空间,其结构反映了单细胞分辨率的网络拓扑结构。我们构建了一个多尺度的人类细胞图谱网络,并应用AWARE来学习支持细胞类型和组织层次的蛋白质、细胞类型和组织嵌入。我们证明了AWARE在预测蛋白质是否在疾病中发生改变以及这种关联最有可能在人体中表现出来的新任务上的实用性。为此,AWARE比没有上下文信息的通用嵌入至少高出12.5%,这表明AWARE有潜力揭示蛋白质在疾病中的上下文依赖作用。

英文摘要:

Spatial context is central to understanding health and disease. Yet reference protein interaction networks lack such contextualization, thereby limiting the study of where protein interactions likely occur in the human body and how they may be altered in disease. Contextualized protein interactions could better characterize genes with disease-specific interactions and elucidate diseases' manifestation in specific cell types. Here, we introduce AWARE, a graph neural message passing approach to inject cellular and tissue context into protein embeddings. AWARE optimizes for a multi-scale embedding space, whose structure reflects network topology at a single-cell resolution. We construct a multi-scale network of the Human Cell Atlas and apply AWARE to learn protein, cell type, and tissue embeddings that uphold cell type and tissue hierarchies. We demonstrate AWARE's utility on the novel task of predicting whether a protein is altered in disease and where that association most likely manifests in the human body. To this end, AWARE outperforms generic embeddings without contextual information by at least 12.5%, showing AWARE's potential to reveal context-dependent roles of proteins in disease.

机构、总结、中文摘要均由AI分析而来,可能存在错误,请以论文正文为准。

↑