In structure-based drug design, scoring functions are often employed to evaluate protein−ligand interactions. A variety of scoring functions have been developed so far, and thus, some objective benchmarks are desired for assessing their strength and weakness. The comparative assessment of scoring functions (CASF) benchmark developed by us provides an answer to this demand. CASF is designed as a "scoring benchmark", where the scoring process is decoupled from the docking process to depict the performance of scoring function more precisely. Here, we describe the latest update of this benchmark, i.e., CASF-2016. Each scoring function is still evaluated by four metrics, including "scoring power", "ranking power", "docking power", and "screening power". Nevertheless, the evaluation methods have been improved considerably in several aspects. A new test set is compiled, which consists of 285 protein−ligand complexes with high-quality crystal structures and reliable binding constants. A panel of 25 scoring functions are tested on CASF-2016 as a demonstration. Our results reveal that the performance of current scoring functions is more promising in terms of docking power than scoring, ranking, and screening power. Scoring power is somewhat correlated with ranking power, so are docking power and screening power. The results obtained on CASF-2016 may provide valuable guidance for the end users to make smart choices among available scoring functions. Moreover, CASF is created as an open-access benchmark so that other researchers can utilize it to test a wider range of scoring functions. The complete CASF-2016 benchmark will be released on the PDBbind-CN web server (http://www.pdbbind-cn.org/casf.asp/) once this article is published.

Figure 1: This 320-frame sequence of dance motion is choreographed from (1) the starting frame, (2) the ending frame and (3) the learnt motion texture from motion captured dance data. Four motion textons are generated from the motion texture and then used to synthesize all the frames in this sequence. A number of key frames are also shown in the figure to demonstrate that the synthesized motion is natural, smooth and realistic (Two red lines indicate the trajectories of the right hand and right foot). AbstractIn this paper, we describe a novel technique, called motion texture, for synthesizing complex human-figure motion (e.g., dancing) that is statistically similar to the original motion captured data. We define motion texture as a set of motion textons and their distribution, which characterize the stochastic and dynamic nature of the captured motion. Specifically, a motion texton is modeled by a linear dynamic system (LDS) while the texton distribution is represented by a transition matrix indicating how likely each texton is switched to another. We have designed a maximum likelihood algorithm to learn the motion textons and their relationship from the captured dance motion. The learnt motion texture can then be used to generate new animations automatically and/or edit animation sequences interactively. Most interestingly, motion texture can be manipulated at different levels, either by changing the fine details of a specific motion at the texton level or by designing a new choreography at the distribution level. Our approach is demonstrated by many synthesized sequences of visually compelling dance motion.

P-glycoprotein (P-gp), a drug efflux pump, affects the bioavailability of therapeutic drugs and plays a potentially important role in clinical drug-drug interactions. Classification of candidate drugs as substrates or inhibitors of the carrier protein is of crucial importance in drug development. Accurate classification is difficult to achieve due to two major factors: i. The extreme diversity of substrates and the presence of multiple binding sites complicate the understanding of the mechanisms behind and hinder the development of a true, conclusive quantitative structure-activity relationship (QSAR) for P-gp substrates. ii. Both inhibitors and substrates interact with the same binding site of P-gp, as a result, it is not surprising that both share many common structural features. In this work, an unsupervised machine learning approach based on the Kohonen self-organizing maps (SOM) was explored, which incorporated a predefined set of physicochemical descriptors encoding the key molecular properties capable of discerning a substrate from an inhibitor. The SOM model can discriminate between substrates and inhibitors with an average accuracy of 82.3%. The current results show that the SOM-based method provides a potential in silico model for virtual screening.

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In this paper, we consider the problem of leveraging existing fully labeled categories to improve the weakly supervised detection (WSD) of new object categories, which we refer to as mixed supervised detection (MSD). Different from previous MSD methods that directly transfer the pre-trained object detectors from existing categories to new categories, we propose a more reasonable and robust objectness transfer approach for MSD. In our framework, we first learn domain-invariant objectness knowledge from the existing fully labeled categories. The knowledge is modeled based on invariant features that are robust to the distribution discrepancy between the existing categories and new categories; therefore the resulting knowledge would generalize well to new categories and could assist detection models to reject distractors (e.g., object parts) in weakly labeled images of new categories. Under the guidance of learned objectness knowledge, we utilize multiple instance learning (MIL) to model the concepts of both objects and distractors and to further improve the ability of rejecting distractors in weakly labeled images. Our robust objectness transfer approach outperforms the existing MSD methods, and achieves state-of-the-art results on the challenging ILSVRC2013 detection dataset and the PASCAL VOC datasets.

Single-cell RNA sequencing (scRNA-seq) is a powerful tool for characterizing the cell-to-cell variation and cellular dynamics in populations which appear homogeneous otherwise in basic and translational biological research. However, significant challenges arise in the analysis of scRNA-seq data, including the low signal-to-noise ratio with high data sparsity, potential batch effects, scalability problems when hundreds of thousands of cells are to be analyzed among others. The inherent complexities of scRNA-seq data and dynamic nature of cellular processes lead to suboptimal performance of many currently available algorithms, even for basic tasks such as identifying biologically meaningful heterogeneous subpopulations. In this study, we developed the Latent Cellular Analysis (LCA), a machine learning–based analytical pipeline that combines cosine-similarity measurement by latent cellular states with a graph-based clustering algorithm. LCA provides heuristic solutions for population number inference, dimension reduction, feature selection, and control of technical variations without explicit gene filtering. We show that LCA is robust, accurate, and powerful by comparison with multiple state-of-the-art computational methods when applied to large-scale real and simulated scRNA-seq data. Importantly, the ability of LCA to learn from representative subsets of the data provides scalability, thereby addressing a significant challenge posed by growing sample sizes in scRNA-seq data analysis.

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BackgroundMany content-based statistical features of secondary structural elements (CBF-PSSEs) have been proposed and achieved promising results in protein structural class prediction, but until now position distribution of the successive occurrences of an element in predicted secondary structure sequences hasn’t been used. It is necessary to extract some appropriate position-based features of the secondary structural elements for prediction task.ResultsWe proposed some position-based features of predicted secondary structural elements (PBF-PSSEs) and assessed their intrinsic ability relative to the available CBF-PSSEs, which not only offers a systematic and quantitative experimental assessment of these statistical features, but also naturally complements the available comparison of the CBF-PSSEs. We also analyzed the performance of the CBF-PSSEs combined with the PBF-PSSE and further constructed a new combined feature set, PBF11CBF-PSSE. Based on these experiments, novel valuable guidelines for the use of PBF-PSSEs and CBF-PSSEs were obtained.ConclusionsPBF-PSSEs and CBF-PSSEs have a compelling impact on protein structural class prediction. When combining with the PBF-PSSE, most of the CBF-PSSEs get a great improvement over the prediction accuracies, so the PBF-PSSEs and the CBF-PSSEs have to work closely so as to make significant and complementary contributions to protein structural class prediction. Besides, the proposed PBF-PSSE’s performance is extremely sensitive to the choice of parameter k. In summary, our quantitative analysis verifies that exploring the position information of predicted secondary structural elements is a promising way to improve the abilities of protein structural class prediction.