FlyPhoneDB: an integrated web-based resource for cell–cell communication prediction in Drosophila

Abstract

Multicellular organisms rely on cell-cell communication to exchange information necessary for developmental processes and metabolic homeostasis. Cell-cell communication pathways can be inferred from transcriptomic datasets based on ligand-receptor (L-R) expression. Recently, data generated from single cell RNA sequencing (scRNA-seq) have enabled L-R interaction predictions at an unprecedented resolution. While computational methods are available to infer cell-cell communication in vertebrates such a tool does not yet exist for Drosophila. Here, we generated a high confidence list of L-R pairs for the major fly signaling pathways and developed FlyPhoneDB, a quantification algorithm that calculates interaction scores to predict L-R interactions between cells. At the FlyPhoneDB user interface, results are presented in a variety of tabular and graphical formats to facilitate biological interpretation. To demonstrate that FlyPhoneDB can effectively identify active ligands and receptors to uncover cell-cell communication events, we applied FlyPhoneDB to Drosophila scRNA-seq data sets from adult midgut, abdomen, and blood, and demonstrate that FlyPhoneDB can readily identify previously characterized cell-cell communication pathways. Altogether, FlyPhoneDB is an easy-to-use framework that can be used to predict cell-cell communication between cell types from scRNA-seq data in Drosophila.

Disruptions in cell fate decisions and transformed enteroendocrine cells drive intestinal tumorigenesis in Drosophila

“…On the other hand, RPPA is not dependent on this feedback mechanism, suggesting that different Tk-mediated cell communication pathways play a role. RPMA clones, while dependent on transformed EEs to support their growth, are not sensitive to Tk loss, suggesting that the tumor-promoting function of EEs in this particular genetic context is mediated by other signals secreted by the transformed EEs 33,34,67 . Furthermore, our observation that the EE cell fate in RPA clones doesn’t appear to require the transcription factor Scute, which is essential for the EE cell fate in the adult intestine 59, , highlights genotype-dependent differences in EE cell identity in our models.…”

“…Tk must contribute to RPPA clone growth by signaling other cell types in the intestine. For instance, Tk can signal ECs to regulate lipid metabolism through its receptor TkR99D; whether Tk-TkR99D signaling directly regulates ISC proliferation remains to be determined 34,62 .…”

“…Enteroendocrine cells also send signals to other cell types, including ISCs, directly and indirectly [32][33][34] .…”

“…There is evidence for both mechanisms playing a role under normal homeostatic conditions as well 30,31 . Enteroendocrine cells also send signals to other cell types, including ISCs, directly and indirectly 32–34 . For instance, the peptide hormone Tachykinin (Tk) signals the overlying muscle to produce and secrete DILP3, which in turn stimulates ISC proliferation through the Insulin Receptor (InR) 32 .…”

Cancer cachexia: lessons from Drosophila

“…Thus, information about the expression levels of signaling pathway receptors and their target genes in peripheral organs may help identify which and where pathways are activated. Two resources described recently will facilitate such studies: the single-cell atlas of the adult fly ( Li et al, 2022 ), which can be visualized and analyzed through ; and FlyPhoneDB, a web-based resource of cell–cell communication predictions ( Liu et al, 2022 ), with which potential ligand-pathway connections between tissues can be explored systematically.…”