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. 2021 Jul 8;9:638522. doi: 10.3389/fcell.2021.638522

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Copyright © 2021 Machado, Martelli-Junior, Reis, Küchler, Scariot, das Neves and Coletta.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Protein–protein interaction network with the genes associated with non-syndromic cleft palate only (NSCPO). Twenty out of 25 genes formed two nodes interconnected by a validated interaction between LRP6 and MTR. The first encompassed nine genes, including FTCD, MTHFD1, MTHFR, MTR, OFD1, SHMT1, TCN2, TCOF1, and TYMS (P < 1.0e-16), and the second node involved CDH1, COL2A1, COL11A1, COL11A2, CREBBP, GRHL3, LRP6, MSX1, SOX9, TBX1, and TBX22 (P < 1.0e-16). Both nodes were based on curated databases (light blue), experimentally (purple), gene neighborhood (green), gene fusions (red), gene co-occurrence (blue), text mining (light green), co-expression (black), and protein homology (violet). This analysis had an average confidence score of 0.588 (P < 1.0e-16), suggesting a low rate for false-positive interactions.