Accurate prediction of genome-wide RNA secondary structure profile based on extreme gradient boosting.

MOTIVATION: RNA secondary structure plays a vital role in fundamental cellular processes, and identification of RNA secondary structure is a key step to understand RNA functions. Recently, a few experimental methods were developed to profile genome-wide RNA secondary structure, i.e. the pairing probability of each nucleotide, through high-throughput sequencing techniques. However, these high-throughput methods have low precision and cannot cover all nucleotides due to limited sequencing coverage. RESULTS: Here, we have developed a new method for the prediction of genome-wide RNA secondary structure profile from RNA sequence based on the extreme gradient boosting technique. The method achieves predictions with areas under the receiver operating characteristic curve (AUC) >0.9 on three different datasets, and AUC of 0.888 by another independent test on the recently released Zika virus data. These AUCs are consistently >5% greater than those by the CROSS method recently developed based on a shallow neural network. Further analysis on the 1000 Genome Project data showed that our predicted unpaired probabilities are highly correlated (>0.8) with the minor allele frequencies at synonymous, non-synonymous mutations, and mutations in untranslated regions, which were higher than those generated by RNAplfold. Moreover, the prediction over all human mRNA indicated a consistent result with previous observation that there is a periodic distribution of unpaired probability on codons. The accurate predictions by our method indicate that such model trained on genome-wide experimental data might be an alternative for analytical methods. AVAILABILITY AND IMPLEMENTATION: The GRASP is available for academic use at https://github.com/sysu-yanglab/GRASP. SUPPLEMENTARY INFORMATION: Supplementary data are available online.

DLIGAND2: an improved knowledge-based energy function for protein-ligand interactions using the distance-scaled, finite, ideal-gas reference state.

Performance of structure-based molecular docking largely depends on the accuracy of scoring functions. One important type of scoring functions are knowledge-based potentials derived from known three-dimensional structures of proteins and/or protein-ligand complex structures. This study seeks to improve a knowledge-based protein-ligand potential based on a distance-scale finite ideal-gas reference (DFIRE) state (DLIGAND) by expanding the representation of protein atoms from 13 mol2 atom types to 167 residue-specific atom types, and employing a recently updated dataset containing 12,450 monomer protein chains for training. We found that the updated version DLIGAND2 has a consistent improvement over DLIGAND in predicting binding affinities for either native complex structures or docking-generated poses. More importantly, DLIGAND2 has a 52% increase over DLIGAND in enrichment factors in top 1% predictions based on the DUD-E decoy set, and consistently improves over Autodock Vina and other statistical energy functions in all three benchmark tests. We further found that DLIGAND2 outperforms empirical and machine-learning methods compared for virtual screening on new targets that are not homologous to the DUD-E training set. Given the best performance as a parameter-free statistical potential and among the best in all performance measures, DLIGAND2 should be useful for re-assessing the poses generated by docking software, or acting as one term in other scoring functions. The program is available at https://github.com/sysu-yanglab/DLIGAND2 .