To rapidly and systematically identify critical genes, we performed a high-throughput siRNA screen and statistical and deep learning analyses to determine changes in NC- versus non-NC-derived human cell line behaviors.<h4>Results</h4>We find 14 out of 45 genes significantly reduced c8161 melanoma cell migration; four of the 14 genes altered leader cell motility (BMP4, ITGB1, KCNE3, and RASGRP1). This evidence concerns the gene KCNE3 and melanoma.