Chenggang Clarence Yan

Bio: Chenggang Clarence Yan is an academic researcher from Tsinghua University. The author has contributed to research in topics: Semantic similarity & Coding tree unit. The author has an hindex of 9, co-authored 15 publications receiving 1735 citations. Previous affiliations of Chenggang Clarence Yan include Hangzhou Dianzi University & Chinese Academy of Sciences.

Drug–target interaction prediction: databases, web servers and computational models

Abstract: Identification of drug-target interactions is an important process in drug discovery. Although high-throughput screening and other biological assays are becoming available, experimental methods for drug-target interaction identification remain to be extremely costly, time-consuming and challenging even nowadays. Therefore, various computational models have been developed to predict potential drug-target associations on a large scale. In this review, databases and web servers involved in drug-target identification and drug discovery are summarized. In addition, we mainly introduced some state-of-the-art computational models for drug-target interactions prediction, including network-based method, machine learning-based method and so on. Specially, for the machine learning-based method, much attention was paid to supervised and semi-supervised models, which have essential difference in the adoption of negative samples. Although significant improvements for drug-target interaction prediction have been obtained by many effective computational models, both network-based and machine learning-based methods have their disadvantages, respectively. Furthermore, we discuss the future directions of the network-based drug discovery and network approach for personalized drug discovery based on personalized medicine, genome sequencing, tumor clone-based network and cancer hallmark-based network. Finally, we discussed the new evaluation validation framework and the formulation of drug-target interactions prediction problem by more realistic regression formulation based on quantitative bioactivity data.

Long non-coding RNAs and complex diseases: from experimental results to computational models

Abstract: LncRNAs have attracted lots of attentions from researchers worldwide in recent decades. With the rapid advances in both experimental technology and computational prediction algorithm, thousands of lncRNA have been identified in eukaryotic organisms ranging from nematodes to humans in the past few years. More and more research evidences have indicated that lncRNAs are involved in almost the whole life cycle of cells through different mechanisms and play important roles in many critical biological processes. Therefore, it is not surprising that the mutations and dysregulations of lncRNAs would contribute to the development of various human complex diseases. In this review, we first made a brief introduction about the functions of lncRNAs, five important lncRNA-related diseases, five critical disease-related lncRNAs and some important publicly available lncRNA-related databases about sequence, expression, function, etc. Nowadays, only a limited number of lncRNAs have been experimentally reported to be related to human diseases. Therefore, analyzing available lncRNA-disease associations and predicting potential human lncRNA-disease associations have become important tasks of bioinformatics, which would benefit human complex diseases mechanism understanding at lncRNA level, disease biomarker detection and disease diagnosis, treatment, prognosis and prevention. Furthermore, we introduced some state-of-the-art computational models, which could be effectively used to identify disease-related lncRNAs on a large scale and select the most promising disease-related lncRNAs for experimental validation. We also analyzed the limitations of these models and discussed the future directions of developing computational models for lncRNA research.

Efficient Parallel Framework for HEVC Motion Estimation on Many-Core Processors

Abstract: High Efficiency Video Coding (HEVC) provides superior coding efficiency than previous video coding standards at the cost of increasing encoding complexity. The complexity increase of motion estimation (ME) procedure is rather significant, especially when considering the complicated partitioning structure of HEVC. To fully exploit the coding efficiency brought by HEVC requires a huge amount of computations. In this paper, we analyze the ME structure in HEVC and propose a parallel framework to decouple ME for different partitions on many-core processors. Based on local parallel method (LPM), we first use the directed acyclic graph (DAG)-based order to parallelize coding tree units (CTUs) and adopt improved LPM (ILPM) within each CTU (DAGILPM), which exploits the CTU-level and prediction unit (PU)-level parallelism. Then, we find that there exist completely independent PUs (CIPUs) and partially independent PUs (PIPUs). When the degree of parallelism (DP) is smaller than the maximum DP of DAGILPM, we process the CIPUs and PIPUs, which further increases the DP. The data dependencies and coding efficiency stay the same as LPM. Experiments show that on a 64-core system, compared with serial execution, our proposed scheme achieves more than 30 and 40 times speedup for 1920 × 1080 and 2560 × 1600 video sequences, respectively.

WBSMDA: Within and Between Score for MiRNA-Disease Association prediction.

Abstract: Increasing evidences have indicated that microRNAs (miRNAs) are functionally associated with the development and progression of various complex human diseases. However, the roles of miRNAs in multiple biological processes or various diseases and their underlying molecular mechanisms still have not been fully understood yet. Predicting potential miRNA-disease associations by integrating various heterogeneous biological datasets is of great significance to the biomedical research. Computational methods could obtain potential miRNA-disease associations in a short time, which significantly reduce the experimental time and cost. Considering the limitations in previous computational methods, we developed the model of Within and Between Score for MiRNA-Disease Association prediction (WBSMDA) to predict potential miRNAs associated with various complex diseases. WBSMDA could be applied to the diseases without any known related miRNAs. The AUC of 0.8031 based on Leave-one-out cross validation has demonstrated its reliable performance. WBSMDA was further applied to Colon Neoplasms, Prostate Neoplasms and Lymphoma for the identification of their potential related miRNAs. As a result, 90%, 84% and 80% of predicted miRNA-disease pairs in the top 50 prediction list for these three diseases have been confirmed by recent experimental literatures, respectively. It is anticipated that WBSMDA would be a useful resource for potential miRNA-disease association identification.

HGIMDA: Heterogeneous graph inference for miRNA-disease association prediction

Abstract: // Xing Chen 1, * , Chenggang Clarence Yan 2, * , Xu Zhang 3 , Zhu-Hong You 4 , Yu-An Huang 5 , Gui-Ying Yan 6 1 School of Information and Electrical Engineering, China University of Mining and Technology, Xuzhou, China 2 Institute of Information and Control, Hangzhou Dianzi University, Hangzhou, China 3 School of Mechanical, Electrical & Information Engineering, Shandong University, Weihai, China 4 School of Computer Science and Technology, China University of Mining and Technology, Xuzhou, China 5 Department of Computing, Hong Kong Polytechnic University, Hong Kong, China 6 Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, China * The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors. Correspondence to: Xing Chen, email: xingchen@amss.ac.cn Gui-Ying Yan, email: yangy@amss.ac.cn Keywords: microRNA, disease, microRNA-disease association, heterogeneous network, similarity Received: May 12, 2016 Accepted: July 28, 2016 Published: August 12, 2016 ABSTRACT Recently, microRNAs (miRNAs) have drawn more and more attentions because accumulating experimental studies have indicated miRNA could play critical roles in multiple biological processes as well as the development and progression of human complex diseases. Using the huge number of known heterogeneous biological datasets to predict potential associations between miRNAs and diseases is an important topic in the field of biology, medicine, and bioinformatics. In this study, considering the limitations in the previous computational methods, we developed the computational model of Heterogeneous Graph Inference for MiRNA-Disease Association prediction (HGIMDA) to uncover potential miRNA-disease associations by integrating miRNA functional similarity, disease semantic similarity, Gaussian interaction profile kernel similarity, and experimentally verified miRNA-disease associations into a heterogeneous graph. HGIMDA obtained AUCs of 0.8781 and 0.8077 based on global and local leave-one-out cross validation, respectively. Furthermore, HGIMDA was applied to three important human cancers for performance evaluation. As a result, 90% (Colon Neoplasms), 88% (Esophageal Neoplasms) and 88% (Kidney Neoplasms) of top 50 predicted miRNAs are confirmed by recent experiment reports. Furthermore, HGIMDA could be effectively applied to new diseases and new miRNAs without any known associations, which overcome the important limitations of many previous computational models.

A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response

Abstract: Recently, more than 1000 large intergenic noncoding RNAs (lincRNAs) have been reported. These RNAs are evolutionarily conserved in mammalian genomes and thus presumably function in diverse biological processes. Here, we report the identification of lincRNAs that are regulated by p53. One of these lincRNAs (lincRNA-p21) serves as a repressor in p53-dependent transcriptional responses. Inhibition of lincRNA-p21 affects the expression of hundreds of gene targets enriched for genes normally repressed by p53. The observed transcriptional repression by lincRNA-p21 is mediated through the physical association with hnRNP-K. This interaction is required for proper genomic localization of hnRNP-K at repressed genes and regulation of p53 mediates apoptosis. We propose a model whereby transcription factors activate lincRNAs that serve as key repressors by physically associating with repressive complexes and modulate their localization to sets of previously active genes.

Counting on natural products for drug design

Abstract: Natural products and their molecular frameworks have a long tradition as valuable starting points for medicinal chemistry and drug discovery. Recently, there has been a revitalization of interest in the inclusion of these chemotypes in compound collections for screening and achieving selective target modulation. Here we discuss natural-product-inspired drug discovery with a focus on recent advances in the design of synthetically tractable small molecules that mimic nature's chemistry. We highlight the potential of innovative computational tools in processing structurally complex natural products to predict their macromolecular targets and attempt to forecast the role that natural-product-derived fragments and fragment-like natural products will play in next-generation drug discovery.

MicroRNAs: Target Recognition and Regulatory Functions

Abstract: MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients.

Abstract: The proper validation of prognostic biomarkers is an important clinical issue in breast cancer research. MicroRNAs (miRNAs) have emerged as a new class of promising breast cancer biomarkers. In the present work, we developed an integrated online bioinformatic tool to validate the prognostic relevance of miRNAs in breast cancer. A database was set up by searching the GEO, EGA, TCGA, and PubMed repositories to identify datasets with published miRNA expression and clinical data. Kaplan–Meier survival analysis was performed to validate the prognostic value of a set of 41 previously published survival-associated miRNAs. All together 2178 samples from four independent datasets were integrated into the system including the expression of 1052 distinct human miRNAs. In addition, the web-tool allows for the selection of patients, which can be filtered by receptors status, lymph node involvement, histological grade, and treatments. The complete analysis tool can be accessed online at: www.kmplot.com/mirpower . We used this tool to analyze a large number of deregulated miRNAs associated with breast cancer features and outcome, and confirmed the prognostic value of 26 miRNAs. A significant correlation in three out of four datasets was validated only for miR-29c and miR-101. In summary, we established an integrated platform capable to mine all available miRNA data to perform a survival analysis for the identification and validation of prognostic miRNA markers in breast cancer.

MicroRNAs and complex diseases: from experimental results to computational models.

Abstract: Circular RNAs (circRNAs) are a class of single-stranded, covalently closed RNA molecules with a variety of biological functions. Studies have shown that circRNAs are involved in a variety of biological processes and play an important role in the development of various complex diseases, so the identification of circRNA-disease associations would contribute to the diagnosis and treatment of diseases. In this review, we summarize the discovery, classifications and functions of circRNAs and introduce four important diseases associated with circRNAs. Then, we list some significant and publicly accessible databases containing comprehensive annotation resources of circRNAs and experimentally validated circRNA-disease associations. Next, we introduce some state-of-the-art computational models for predicting novel circRNA-disease associations and divide them into two categories, namely network algorithm-based and machine learning-based models. Subsequently, several evaluation methods of prediction performance of these computational models are summarized. Finally, we analyze the advantages and disadvantages of different types of computational models and provide some suggestions to promote the development of circRNA-disease association identification from the perspective of the construction of new computational models and the accumulation of circRNA-related data.