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The first knowledge base for ligand-receptor pair annotations was built upon high confident annotations from literature review by experts in the field. To expand the knowledge base for Drosophila, we continued to add high-confident L-R pairs from literature review.

We've also collected L-R pairs curated for human and mouse by CellTalkDB. We then mapped the relevant mammalian ligands and receptors to Drosophila orthologs using DIOPT. Through DIOPT analysis, we identified 2,061 fly pairs that are orthologous to these human and mouse sets. We applied AlphaFold-Multimer to the 2,053 pairs L-R pairs which did not have direct experimental evidence, leading to the predictions of direct PPIs in 476 additional pairs. The L-R pairs curated in mammalians that are predicted to interact directly by Alphafold Multimer are assigned a moderate-confidence rank to differentiate them from high-confident pairs curated from Drosophila literature.

All in all, we produce an updated comprehensive set of 1,747 receptor-ligand pairs with 376 ligands and 449 receptors.