Guoqing Liu

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Papers by Guoqing Liu

DNA physical properties outperform sequence compositional information in classifying nucleosome-enriched and -depleted regions

Genomics, 2018

The nucleosome is the fundamental structural unit of eukaryotic chromatin and plays an essential ... more The nucleosome is the fundamental structural unit of eukaryotic chromatin and plays an essential role in the epigenetic regulation of cellular processes, such as DNA replication, recombination, and transcription. Hence, it is important to identify nucleosome positions in the genome. Our previous model based on DNA deformation energy, in which a set of DNA physical descriptors was used, performed well in predicting nucleosome dyad positions and occupancy. In this study, we established a machine-learning model for predicting nucleosome occupancy in order to further verify the physical descriptors. Results showed that (1) our model outperformed several other sequence compositional information-based models, indicating a stronger dependence of nucleosome positioning on DNA physical properties; (2) nucleosome-enriched and-depleted regions have distinct features in terms of DNA physical descriptors like sequence-dependent flexibility and equilibrium structure parameters; (3) gene transcription start sites and termination sites can be well characterized with the distribution patterns of the physical descriptors, indicating the regulatory role of DNA physical properties in gene transcription. In addition, we developed a web server for the model, which is freely accessible at http://lingroup.cn/server/iNuc-force/.

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Transcriptomic Data Analyses Reveal a Reprogramed Lipid Metabolism in HCV-Derived Hepatocellular Cancer

Frontiers in Cell and Developmental Biology, 2020

Reprograming lipid metabolism, one of the major metabolic alterations in cancer, is believed to p... more Reprograming lipid metabolism, one of the major metabolic alterations in cancer, is believed to play an essential role in cancer development, but the exact molecular mechanism remains elusive. Here, we present a computational study of transcriptomic data of HCC with HCV etiology to investigate how lipid metabolism alters during HCC progression. Our analyses reveal that: (1) cancer tissue cells tend to synthesize fatty acids de novo and its phospholipid derivatives; (2) lipid catabolism and fatty acid oxidation are remarkably down-regulated in HCC; (3) the lipid metabolism in HCC is largely independent of lipids in blood circulation; (4) stage-specific co-expression networks for lipid metabolic genes were identified during HCC progression; and (5) the expression levels of several lipid metabolic genes that are differentially expressed or coexpressed specifically at the HCC stage have a strong correlation with cancer survival. Overall, the results provide detailed information about the reprogramed lipid metabolism in HCV-derived HCC.

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Physical properties of DNA may direct the binding of nucleoid-associated proteins along the E. coli genome

Mathematical biosciences, Jan 4, 2018

Nucleoid-associated proteins (NAPs) play important roles in both chromosome packaging and gene re... more Nucleoid-associated proteins (NAPs) play important roles in both chromosome packaging and gene regulation in bacteria. The underlying mechanisms, however, remain elusive particularly for how NAPs contribute to chromosome packaging. We report here a characterization of the binding sites for several major NAPs in E. coli, namely HNS, IHF, Fis, Dps and a non-NAP protein, FNR, in terms of the physical properties of their binding DNA. Our study shows that (i) as compared with flanking regions, the binding sites for IHF, Fis and FNR tend to have high intrinsic curvature, while no characterized pattern of intrinsic curvature distribution around those of HNS and Dps; (ii) all the binding sites analyzed in this study except those of HNS are characterized by high structural flexibility; (iii) the intrinsic curvature and flexibility at the binding sites for Fis and IHF are found to be coupled with the sequence specificity required in their binding, while the physical properties of the binding ...

format_quoteNAPs prefer binding to intrinsically curved DNA regions, indicating structural dependencies in their binding mechanisms.format_quote

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DNA Sequence-Dependent Properties of Nucleosome Positioning in Regions of Distinct Chromatin States in Mouse Embryonic Stem Cells

International Journal of Molecular Sciences

Chromatin architecture is orchestrated, and plays crucial roles during the developmental process ... more Chromatin architecture is orchestrated, and plays crucial roles during the developmental process by regulating gene expression. In embryonic stem cells (ESCs), three types of chromatin states, including active, repressive and poised states, were previously identified and characterized with specific chromatin modification marks and different transcription activity, but it is largely unknown how nucleosomes are organized in these chromatin states. In this study, by using a DNA deformation energy model, we investigated the sequence-dependent nucleosome organization within the chromatin states in mouse ESCs. The results revealed that: (1) compared with poised genes, active genes are characterized with a higher level of nucleosome occupancy around their transcription start sites (TSS) and transcription termination sites (TTS), and both types of genes do not have a nucleosome-depleted region at their TTS, contrasting with the MNase-seq based result; (2) based on our previous DNA bending e...

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Identification of miR-200c and miR141-Mediated lncRNA-mRNA Crosstalks in Muscle-Invasive Bladder Cancer Subtypes

Frontiers in Genetics, 2018

Basal and luminal subtypes of muscle-invasive bladder cancer (MIBC) have distinct molecular profi... more Basal and luminal subtypes of muscle-invasive bladder cancer (MIBC) have distinct molecular profiles and heterogeneous clinical behaviors. The interactions between mRNAs and lncRNAs, which might be regulated by miRNAs, have crucial roles in many cancers. However, the miRNA-dependent crosstalk between lncRNA and mRNA in specific MIBC subtypes still remains unclear. In this study, we first classified MIBC into two conservative subtypes using miRNA, mRNA and lncRNA expression data derived from The Cancer Genome Atlas. Then we investigated subtype-related biological pathways and evaluated the subtype classification performance using Decision Trees, Random Forest and eXtreme Gradient Boosting (XGBoost). At last, we explored potential miRNA-mediated lncRNA-mRNA crosstalks based on co-expression analysis. Our results show that: (1) the luminal subtype is primarily characterized by upregulation of metabolism-related pathways while the basal subtype is predominantly characterized by upregulation of epithelial-mesenchymal transition, metastasis, and immune system process-related pathways; (2) the XGBoost prediction model is consistently robust for classification of the molecular subtypes of MIBC across four datasets (The area under the ROC curve > 0.9); (3) the expression levels of the molecules in the miR-200c and miR141-mediated lncRNA-mRNA crosstalks differ considerably between the two subtypes and have close relationships with the prognosis of MIBC. The miR-200c and miR-141-dependent mRNA-lncRNA crosstalks might be of great significance in tumorigenesis and tumor progression and may serve as the novel prognostic predictors and classification markers of MIBC subtypes.

format_quotemiR-200c and miR-141-dependent interactions may serve as novel prognostic markers and predictors for MIBC subtypes.format_quote

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The implication of DNA bending energy for nucleosome positioning and sliding

Scientific reports, Jan 11, 2018

Nucleosome not only directly affects cellular processes, such as DNA replication, recombination, ... more Nucleosome not only directly affects cellular processes, such as DNA replication, recombination, and transcription, but also severs as a fundamentally important target of epigenetic modifications. Our previous study indicated that the bending property of DNA is important in nucleosome formation, particularly in predicting the dyad positions of nucleosomes on a DNA segment. Here, we investigated the role of bending energy in nucleosome positioning and sliding in depth to decipher sequence-directed mechanism. The results show that bending energy is a good physical index to predict the free energy in the process of nucleosome reconstitution in vitro. Our data also imply that there are at least 20% of the nucleosomes in budding yeast do not adopt canonical positioning, in which underlying sequences wrapped around histones are structurally symmetric. We also revealed distinct patterns of bending energy profile for distinctly organized chromatin structures, such as well-positioned nucleos...

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