02197nas a2200181   4500008004100000022001400041245011200055210006900167260001600236490000700252520151000259100002001769700002201789700003501811700002001846700002001866856012901886       2023                        eng d  a2079-773700aSigPrimedNet: A Signaling-Informed Neural Network for scRNA-seq Annotation of Known and Unknown Cell Types.0 aSigPrimedNet A SignalingInformed Neural Network for scRNAseq Ann  c2023 Apr 100 v123 a<p>Single-cell RNA sequencing is increasing our understanding of the behavior of complex tissues or organs, by providing unprecedented details on the complex cell type landscape at the level of individual cells. Cell type definition and functional annotation are key steps to understanding the molecular processes behind the underlying cellular communication machinery. However, the exponential growth of scRNA-seq data has made the task of manually annotating cells unfeasible, due not only to an unparalleled resolution of the technology but to an ever-increasing heterogeneity of the data. Many supervised and unsupervised methods have been proposed to automatically annotate cells. Supervised approaches for cell-type annotation outperform unsupervised methods except when new (unknown) cell types are present. Here, we introduce SigPrimedNet an artificial neural network approach that leverages (i) efficient training by means of a sparsity-inducing signaling circuits-informed layer, (ii) feature representation learning through supervised training, and (iii) unknown cell-type identification by fitting an anomaly detection method on the learned representation. We show that SigPrimedNet can efficiently annotate known cell types while keeping a low false-positive rate for unseen cells across a set of publicly available datasets. In addition, the learned representation acts as a proxy for signaling circuit activity measurements, which provide useful estimations of the cell functionalities.</p>1 aGundogdu, Pelin1 aAlamo, Inmaculada1 aNepomuceno-Chamorro, Isabel, A1 aDopazo, Joaquin1 aLoucera, Carlos  uhttp://clinbioinfosspa.es/content/sigprimednet-signaling-informed-neural-network-scrna-seq-annotation-known-and-unknown-cell