Human absorbable microRNA prediction based on an ensemble manifold ranking model

MicroRNAs, a class of short non-coding RNAs, are able to regulate more than half of human genes and affect many fundamental biological processes. It has been long considered synthesized endogenously until very recent discoveries showing that human can absorb exogenous microRNAs from dietary resources. This finding has raised a challenge scientific question: which exogenous microRNAs can be integrated into human circulation and possibly exert functions in human? Here we present a well-designed ensemble manifold ranking model for identifying human absorbable exogenous miRNAs from 14 common dietary species. Specifically, we have analyzed 4,910 dietary microRNAs with 1,120 features derived based on the microRNA sequence and structure. In total, 70 discriminative features were selected to characterize the circulating microRNAs in human and have been used to infer the possibility of a certain exogenous microRNA getting integrated into human circulation. Finally, 461 dietary microRNAs have been identified as transportable exogenous microRNAs. To assess the performance of our ensemble model, we have validated the top predictions through a milk-feeding study. In addition, 26 microRNAs from two virus species were predicted as transportable and have been validated in two external experiments. The results demonstrate the data-driven computational model is highly promising to study transportable microRNAs while bypassing the complex mechanistic details.