*2.10. Gene Ontology, Pathway Enrichment, and Protein-Protein Interaction Networks*

Grouping of EV proteins into cellular components was accomplished using Gene Ontology (GO) analysis (http://geneontology.org/) and the Funrich database (https://FunRich.org). EV protein functions and utilities were determined using DAVID ((https://david.ncifcrf.gov/) analysis of The Kyoto Encyclopedia of Genes and Genomes (KEGG; https://www.genome.jp/kegg/). Search Tool for the Retrieval of Interacting Genes (STRING, https://string-db.org/) was employed to determine interactions among EV proteins using a minimum interaction score of 0.4 for the D4 mHSC EV dataset, and 0.9 for the P1 mHSC or LX-2 EV datasets. The Markov Cluster Algorithm method with an inflation parameter of 2 was applied for clustering. These analyses were each performed with a criterion FDR < 0.05.
