MysiRNA: improving siRNA efficacy prediction using a machine-learning model combining multi-tools and whole stacking energy (ΔG)

Abstract

The investigation of small interfering RNA (siRNA) and its posttranscriptional gene-regulation has become an extremely important research topic, both for fundamental reasons and for potential longer-term therapeutic benefits. Several factors affect the functionality of siRNA including positional preferences, target accessibility and other thermodynamic features. State of the art tools aim to optimize the selection of target siRNAs by identifying those that may have high experimental inhibition. Such tools implement artificial neural network models as Biopredsi and ThermoComposition21, and linear regression models as DSIR, i-Score and Scales, among others. However, all these models have limitations in performance. In this work, a neural-network trained new siRNA scoring/efficacy prediction model was developed based on combining two existing scoring algorithms (ThermoComposition21 and i-Score), together with the whole stacking energy (ΔG), in a multi-layer artificial neural network. These three parameters were chosen after a comparative combinatorial study between five well known tools. Our developed model, 'MysiRNA' was trained on 2431 siRNA records and tested using three further datasets. MysiRNA was compared with 11 alternative existing scoring tools in an evaluation study to assess the predicted and experimental siRNA efficiency where it achieved the highest performance both in terms of correlation coefficient (R(2)=0.600) and receiver operating characteristics analysis (AUC=0.808), improving the prediction accuracy by up to 18% with respect to sensitivity and specificity of the best available tools. MysiRNA is a novel, freely accessible model capable of predicting siRNA inhibition efficiency with improved specificity and sensitivity. This multiclassifier approach could help improve the performance of prediction in several bioinformatics areas. MysiRNA model, part of MysiRNA-Designer package [1], is expected to play a key role in siRNA selection and evaluation.