Publications by authors named "Yubin Xie"

26 Publications

  • Page 1 of 1

Convalescent plasma to treat COVID-19: clinical experience and efficacy.

Aging (Albany NY) 2021 03 18;13(6):7758-7766. Epub 2021 Mar 18.

Hunan Engineering Research Center of Obstetrics and Gynecological Disease, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.

The recent outbreak of COVID-19 in the world is currently a big threat to global health and economy. Convalescent plasma has been confirmed effective against the novel corona virus in preliminary studies. In this paper, we first described the therapeutic schedule, antibody detection method, indications, contraindications of the convalescent plasmas and reported the effectiveness of convalescent plasma therapy by a retrospective cohort study.
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http://dx.doi.org/10.18632/aging.202795DOI Listing
March 2021

autoRPA: A web server for constructing cancer staging models by recursive partitioning analysis.

Comput Struct Biotechnol J 2020 10;18:3361-3367. Epub 2020 Nov 10.

State Key Laboratory of Oncology in South China, Cancer Center, Collaborative Innovation Center for Cancer Medicine, School of Life Sciences, Sun Yat-sen University, Guangzhou 510060, China.

Cancer staging provides a common language that is used to describe the severity of an individual's cancer, which plays a critical role in optimizing cancer treatment. Recursive partitioning analysis (RPA) is the most widely accepted method for cancer staging. Despite its widespread use, to date, only limited tools have been developed to implement the RPA algorithm for cancer staging. Moreover, most of the available tools can be accessed only from command lines and also lack visualization, making them difficult for clinical investigators without programing skills to use. Therefore, we developed a web server called autoRPA that is dedicated to supporting the construction of prognostic staging models and performance comparisons among different staging models. Based on the RPA algorithm and log-rank test statistics, autoRPA can establish a decision-making tree from survival data and provide clinicians an intuitive method to further prune the decision tree. Moreover, autoRPA can evaluate the contribution of each submitted covariate that is involved in the grouping process and help identify factors that significantly contribute to cancer staging. Four indicators, including hazard consistency, hazard discrimination, percentage of variation explained, and sample size balance, are introduced to validate the performance of the designed staging models. In addition, autoRPA can also be used to compare the performance of different prognostic staging models using a standard bootstrap evaluation method. The web server of autoRPA is freely available at http://rpa.renlab.org.
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http://dx.doi.org/10.1016/j.csbj.2020.10.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688999PMC
November 2020

PTMsnp: A Web Server for the Identification of Driver Mutations That Affect Protein Post-translational Modification.

Front Cell Dev Biol 2020 10;8:593661. Epub 2020 Nov 10.

Precision Medicine Institute, The First Affiliated Hospital, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.

High-throughput sequencing technologies have identified millions of genetic mutations in multiple human diseases. However, the interpretation of the pathogenesis of these mutations and the discovery of driver genes that dominate disease progression is still a major challenge. Combining functional features such as protein post-translational modification (PTM) with genetic mutations is an effective way to predict such alterations. Here, we present PTMsnp, a web server that implements a Bayesian hierarchical model to identify driver genetic mutations targeting PTM sites. PTMsnp accepts genetic mutations in a standard variant call format or tabular format as input and outputs several interactive charts of PTM-related mutations that potentially affect PTMs. Additional functional annotations are performed to evaluate the impact of PTM-related mutations on protein structure and function, as well as to classify variants relevant to Mendelian disease. A total of 4,11,574 modification sites from 33 different types of PTMs and 1,776,848 somatic mutations from TCGA across 33 different cancer types are integrated into the web server, enabling identification of candidate cancer driver genes based on PTM. Applications of PTMsnp to the cancer cohorts and a GWAS dataset of type 2 diabetes identified a set of potential drivers together with several known disease-related genes, indicating its reliability in distinguishing disease-related mutations and providing potential molecular targets for new therapeutic strategies. PTMsnp is freely available at: http://ptmsnp.renlab.org.
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http://dx.doi.org/10.3389/fcell.2020.593661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683509PMC
November 2020

RMVar: an updated database of functional variants involved in RNA modifications.

Nucleic Acids Res 2021 01;49(D1):D1405-D1412

State Key Laboratory of Oncology in South China, Cancer Center, Collaborative Innovation Center for Cancer Medicine, School of Life Sciences, Sun Yat-sen University, Guangzhou 510060, China.

Distinguishing the few disease-related variants from a massive number of passenger variants is a major challenge. Variants affecting RNA modifications that play critical roles in many aspects of RNA metabolism have recently been linked to many human diseases, such as cancers. Evaluating the effect of genetic variants on RNA modifications will provide a new perspective for understanding the pathogenic mechanism of human diseases. Previously, we developed a database called 'm6AVar' to host variants associated with m6A, one of the most prevalent RNA modifications in eukaryotes. To host all RNA modification (RM)-associated variants, here we present an updated version of m6AVar renamed RMVar (http://rmvar.renlab.org). In this update, RMVar contains 1 678 126 RM-associated variants for 9 kinds of RNA modifications, namely m6A, m6Am, m1A, pseudouridine, m5C, m5U, 2'-O-Me, A-to-I and m7G, at three confidence levels. Moreover, RBP binding regions, miRNA targets, splicing events and circRNAs were integrated to assist investigations of the effects of RM-associated variants on posttranscriptional regulation. In addition, disease-related information was integrated from ClinVar and other genome-wide association studies (GWAS) to investigate the relationship between RM-associated variants and diseases. We expect that RMVar may boost further functional studies on genetic variants affecting RNA modifications.
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http://dx.doi.org/10.1093/nar/gkaa811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779057PMC
January 2021

The Influence of Immune Heterogeneity on the Effectiveness of Immune Checkpoint Inhibitors in Multifocal Hepatocellular Carcinomas.

Clin Cancer Res 2020 Sep 11;26(18):4947-4957. Epub 2020 Jun 11.

Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Purpose: Immune checkpoint inhibitor therapy is emerging as the promising option for patients with advanced hepatocellular carcinoma. We aimed to investigate the heterogeneity of different tumor nodules of the same patient with multifocal hepatocellular carcinomas in response to immunotherapy and its molecular mechanisms.

Experimental Design: We attained 45 surgical tumor samples including 33 small and 12 large nodules from 12 patients with multifocal hepatocellular carcinoma and evaluated genomic and immune heterogeneity among tumors through whole-genome sequencing and RNA sequencing. IHC was performed to validate the expression of immune markers. The responses to anti-programmed cell death protein-1 (PD-1) therapy in patients with multifocal hepatocellular carcinoma were evaluated.

Results: The small and large tumors within the same patient presented with similar genomic characteristics, indicating their same genomic origin. We further found the small tumors had higher immune cell infiltration including more CD8 T cells, M1 macrophages, and monocytes as compared with large tumors. Besides, the expression of interferon signature predictive of response to anti-PD-1 therapy was significantly upregulated in the small tumors. Moreover, the immune pathways were more vigorous along with less active proliferation pathways in the small tumors. In keeping with this, we found that small nodules were more sensitive to anti-PD-1 therapy than large nodules in patients with multifocal hepatocellular carcinoma.

Conclusions: The small tumors in patients with multifocal hepatocellular carcinoma had higher immune cell infiltration and upregulation of immune pathways as compared with the large tumors, which can partially explain the different responses of small and large tumors in the same case to anti-PD-1 therapy.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-3840DOI Listing
September 2020

The clinical effect of plum blossom needle acupuncture with qi-invigorating superficies-consolidating therapy on seborrheic alopecia.

Ann Palliat Med 2020 May 11;9(3):1030-1036. Epub 2020 May 11.

Department of Dermatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.

Background: Seborrheic alopecia (SA) is a common dermatological disease with a long disease course, and treatment for this disease usually exhibits slow effects. Currently, Western medicine treatments have shown some effects; however, they also have certain limitations. In recent years, Chinese medicine has made breakthroughs in treating SA. The efficacy of plum blossom needle acupuncture with qi-invigorating superficies-consolidating therapy for SA was observed, and its clinical effects were investigated in this study.

Methods: A total of 87 patients with SA treated at the First Affiliated Hospital of Guangzhou University of Chinese Medicine from September 2018 to September 2019 were enrolled as the research subjects. They were divided into a Western medicine group and a Chinese medicine group by the random number table method. The 43 patients in the Western medicine group were treated with conventional Western medicine, and the 44 patients in the Chinese medicine group were treated with a comprehensive traditional Chinese medicine regimen of plum blossom needling with qi-invigorating superficies-consolidating therapy. The treatment effects, changes in estradiol (E2) and testosterone (T) levels, and scores for various body signs (hair growth and hair loss) of the two groups before and after treatment were compared.

Results: The difference in total effective rate between the Chinese medicine group and the Western medicine group (95.45% vs. 81.40%) was statistically significant (P<0.05). After treatment, the T levels of both groups were lower than before treatment, and the E2 levels of both groups were higher than before treatment; the difference between the two groups was statistically significant (P<0.05). After treatment, the hair growth and hair loss scores of the two groups were lower than those before treatment, and those of the Chinese medicine group were lower than those of the Western medicine group; the differences were statistically significant (P<0.05).

Conclusions: Plum blossom needle acupuncture combined with qi-invigorating superficies-consolidating therapy is significantly effective for treating patients with SA. It can effectively adjust the patient's hormone levels, improve hair loss, and promote hair growth. It has the advantages of simplicity, tolerability, and low cost. It cures the cause of the disease and is worth promoting.
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http://dx.doi.org/10.21037/apm-20-909DOI Listing
May 2020

Regenerative lineages and immune-mediated pruning in lung cancer metastasis.

Nat Med 2020 02 10;26(2):259-269. Epub 2020 Feb 10.

Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Developmental processes underlying normal tissue regeneration have been implicated in cancer, but the degree of their enactment during tumor progression and under the selective pressures of immune surveillance, remain unknown. Here we show that human primary lung adenocarcinomas are characterized by the emergence of regenerative cell types, typically seen in response to lung injury, and by striking infidelity among transcription factors specifying most alveolar and bronchial epithelial lineages. In contrast, metastases are enriched for key endoderm and lung-specifying transcription factors, SOX2 and SOX9, and recapitulate more primitive transcriptional programs spanning stem-like to regenerative pulmonary epithelial progenitor states. This developmental continuum mirrors the progressive stages of spontaneous outbreak from metastatic dormancy in a mouse model and exhibits SOX9-dependent resistance to natural killer cells. Loss of developmental stage-specific constraint in macrometastases triggered by natural killer cell depletion suggests a dynamic interplay between developmental plasticity and immune-mediated pruning during metastasis.
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http://dx.doi.org/10.1038/s41591-019-0750-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021003PMC
February 2020

Treatment of consistent BRAF/HRAS gene mutation and MYC amplification radiation-induced abdominal wall angiosarcoma with low-dose apatinib: a case report.

BMC Cancer 2019 Dec 5;19(1):1188. Epub 2019 Dec 5.

Cancer Center, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, 510405, Guangzhou, Guangdong, People's Republic of China.

Background: An extremely rare condition, radiation-induced angiosarcoma is characterized by a poor prognosis, high recurrence rate and lack of effective treatment. Herein, we present a case report of a 48-year-old female patient with radiation-induced abdominal wall angiosarcoma who showed a dramatic response to low-dose apatinib.

Case Presentation: The patient, who was diagnosed with cervical squamous cell carcinoma 20 years ago, had received radiotherapy and chemotherapy after operation. Angiosarcomas of the abdominal wall appeared 9 years later. After repeated surgical operations and intravenous chemotherapy for the angiosarcomas, the patient developed tumor recurrence and pulmonary metastasis. The abdominal wall tumors showed repeated rupture and bleeding, with poor wound healing. On evaluation, laboratory findings detected the negative serum tumor markers CEA, CA 125, CA 15-3 and CA 19-9. Imaging showed multiple subcutaneous nodules and masses in the abdominal wall, accompanied by suspected small subpleural nodule at the lower lobe of the right lung. Immunohistochemistry of previous surgical pathology indicated that CD31, ERG and Vim were positive. The result of whole exome sequencing suggested the mutations of BRAF and HRAS, and the amplification of MYC. Based on the above results, the patient was clinically diagnosed with radiation-induced angiosarcoma of the abdominal wall with pulmonary metastasis. The patient was treated with low-dose apatinib and rejected reoperation or chemotherapy.

Results: At the 6-month follow-up visit, the abdominal wall lesions that had previously ruptured stopped bleeding and showed significant shrinkage. Imaging showed that most of the abdominal wall lesions had partially regressed, and some of the lesions on the abdominal wall and the suspected lesion of subpleural nodule at the lower lobe of the right lung had disappeared.

Conclusions: We described this case and reviewed the literature on radiation-related angiosarcoma. Importantly, this case suggests that apatinib may be an effective and sensitive treatment for radiation-induced angiosarcoma even at the lowest dosage, without aggravating the bleeding of lesions.
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http://dx.doi.org/10.1186/s12885-019-6351-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896664PMC
December 2019

BBCancer: an expression atlas of blood-based biomarkers in the early diagnosis of cancers.

Nucleic Acids Res 2020 01;48(D1):D789-D796

State Key Laboratory of Oncology in South China, Cancer Center, Collaborative Innovation Center for Cancer Medicine, School of Life Sciences, Sun Yat-sen University, Guangzhou 510060, China.

The early detection of cancer holds the key to combat and control the increasing global burden of cancer morbidity and mortality. Blood-based screenings using circulating DNAs (ctDNAs), circulating RNA (ctRNAs), circulating tumor cells (CTCs) and extracellular vesicles (EVs) have shown promising prospects in the early detection of cancer. Recent high-throughput gene expression profiling of blood samples from cancer patients has provided a valuable resource for developing new biomarkers for the early detection of cancer. However, a well-organized online repository for these blood-based high-throughput gene expression data is still not available. Here, we present BBCancer (http://bbcancer.renlab.org/), a web-accessible and comprehensive open resource for providing the expression landscape of six types of RNAs, including messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), microRNAs (miRNAs), circular RNAs (circRNAs), tRNA-derived fragments (tRFRNAs) and Piwi-interacting RNAs (piRNAs) in blood samples, including plasma, CTCs and EVs, from cancer patients with various cancer types. Currently, BBCancer contains expression data of the six RNA types from 5040 normal and tumor blood samples across 15 cancer types. We believe this database will serve as a powerful platform for developing blood biomarkers.
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http://dx.doi.org/10.1093/nar/gkz942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145713PMC
January 2020

Controlled-release curcumin attenuates progression of tendon ectopic calcification by regulating the differentiation of tendon stem/progenitor cells.

Mater Sci Eng C Mater Biol Appl 2019 Oct 29;103:109711. Epub 2019 Apr 29.

Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China. Electronic address:

Tendon calcification is a common but intractable problem leading to pain and activity limitation when injury or tendinopathy progresses into the late stage. This is because tendon stem/progenitor cells (TSPCs) can undergo aberrant osteogenic differentiation under inflammatory conditions. This study aims to investigate the effect of curcumin, a natural anti-inflammatory agent, on regulating the differentiation of TSPCs in tendon calcification. With inflammatory stimulation, TSPCs showed higher alkaline phosphatase activity and more frequent formation of mineralized nodules which were verified in the culture system; however, curcumin significantly alleviated these pathological changes. In in vivo function analysis, chitosan microsphere-encapsulated curcumin was delivered to injured sites of rat tendon ectopic calcification model. The inflammation in the tendon tissues of the curcumin group was significantly relieved. Controlled-release curcumin partially rescued tendon calcification and enhanced tendon regeneration in animal model. This study demonstrates that controlled-release curcumin can manipulate the fate decision of TSPCs, and that it promotes the tenogenesis and inhibits the osteogenesis of TSPCs in a pathological microenvironment, which provides a possible new therapeutic strategy for tendon disease.
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http://dx.doi.org/10.1016/j.msec.2019.04.090DOI Listing
October 2019

The testis-specifically expressed Dpep3 is not essential for male fertility in mice.

Gene 2019 Aug 15;711:143925. Epub 2019 Jun 15.

The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, University of Science and Technology of China, Collaborative Innovation Center of Genetics and Development, Hefei 230027, Anhui, China. Electronic address:

More than 2300 genes have been reported to be involved in spermatogenesis but the functional roles of most genes in male fertility remain to be elucidated. In this study, we explored the function of dipeptidase 3 (Dpep3), a gene predicted to be testis-specific, in male fertility of mice. We showed that Dpep3 is evolutionarily conserved in human and mouse along with other eutherians. Its mRNA was exclusively detected in testicular tissue and expressed in testes from 7 days postpartum. To further explore its role in male fertility, we generated Dpep3 knockout mice (Dpep3) using the CRISPR/Cas9 technology and found that the male Dpep3 mice are fertile despite a significant reduction in sperm count. Histology of testis and progression of meiotic prophase I showed no obvious difference between wild-type and Dpep3 mice. All these findings indicate that Dpep3 is not essential for male fertility in mice. These findings will help other researchers to avoid research duplication, save their time and resources to focus on the genes that are indispensable for male fertility.
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http://dx.doi.org/10.1016/j.gene.2019.06.015DOI Listing
August 2019

DeepPhagy: a deep learning framework for quantitatively measuring autophagy activity in .

Autophagy 2020 04 20;16(4):626-640. Epub 2019 Jun 20.

Department of Bioinformatics and Systems Biology, Key Laboratory of Molecular Biophysics of the Ministry of Education, Hubei Bioinformatics and Molecular Imaging Key Laboratory, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.

Seeing is believing. The direct observation of GFP-Atg8 vacuolar delivery under confocal microscopy is one of the most useful end-point measurements for monitoring yeast macroautophagy/autophagy. However, manually labelling individual cells from large-scale sets of images is time-consuming and labor-intensive, which has greatly hampered its extensive use in functional screens. Herein, we conducted a time-course analysis of nitrogen starvation-induced autophagy in wild-type and knockout mutants of 35 AuTophaGy-related () genes in and obtained 1,944 confocal images containing > 200,000 cells. We manually labelled 8,078 autophagic and 18,493 non-autophagic cells as a benchmark dataset and developed a new deep learning tool for autophagy (DeepPhagy), which exhibited superior accuracy in recognizing autophagic cells compared to other existing methods, with an area under the curve (AUC) value of 0.9710 from 10-fold cross-validations. We further used DeepPhagy to automatically analyze all the images and quantitatively classified the autophagic phenotypes of the 35 knockout mutants into 3 classes. The high consistency in our computational and biochemical results indicated the reliability of DeepPhagy for measuring autophagic activity. Moreover, we used DeepPhagy to analyze 3 additional types of autophagic phenotypes, including the targeting of Atg1-GFP to the vacuole, the vacuolar delivery of GFP-Atg19, and the disintegration of autophagic bodies indicated by GFP-Atg8, all with satisfying accuracies. Taken together, our study not only enables the GFP-Atg8 fluorescence assay to become a quantitative measurement for analyzing autophagic phenotypes in but also demonstrates that deep learning-based methods could potentially be applied to different types of autophagy.: accuracy; ALP: alkaline phosphatase; ALR: autophagic lysosomal reformation; : AuTophaGy-related; AUC: area under the curve; CNN: convolutional neural network; Cvt: cytoplasm-to-vacuole targeting; DeepPhagy: deep learning for autophagy; fc_2: second fully connected; GFP: green fluorescent protein; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3 beta; HAT: histone acetyltransferase; HemI: Heat map Illustrator; JRE: Java Runtime Environment; KO: knockout; LRN: local response normalization; : Mathew Correlation Coefficient; OS: operating system; PAS: phagophore assembly site; PC: principal component; PCA: principal component analysis; PPI: protein-protein interaction; : precision; QPSO: Quantum-behaved Particle Swarm Optimization; ReLU: rectified linear unit; RF: random forest; ROC: receiver operating characteristic; ROI: region of interest; SD: systematic derivation; SGD: stochastic gradient descent; : sensitivity; : specificity; SRG: seeded region growing; t-SNE: t-distributed stochastic neighbor embedding; 2D: 2-dimensional; WT: wild-type.
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http://dx.doi.org/10.1080/15548627.2019.1632622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138222PMC
April 2020

lnCAR: A Comprehensive Resource for lncRNAs from Cancer Arrays.

Cancer Res 2019 04 20;79(8):2076-2083. Epub 2019 Feb 20.

State Key Laboratory of Oncology in South China, Cancer Center, Collaborative Innovation Center for Cancer Medicine, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.

Long noncoding RNAs (lncRNA) have emerged as promising biomarkers in cancer diagnosis, treatment, and prognosis. Recent studies suggest that a large number of coding gene expression microarray probes could be reannotated as lncRNAs. Microarray, once the most cutting-edge high-throughput gene expression technology, has been used for thousands of cancer studies and has brought invaluable resources for studying the functions of lncRNA in cancer development. However, a comprehensive lncRNA resource based on microarray data is still lacking. Here, we present lnCAR (lncRNAs from cancer arrays), a comprehensive open resource for providing expression profiles and prognostic landscape of lncRNAs derived from reannotation of public microarray data. Currently, lnCAR contains 52,300 samples for differential expression analysis and 12,883 samples for survival analysis from 10 cancer types. lnCAR allows users to interactively explore any annotated or novel lncRNAs. We believe lnCAR will serve as a valuable resource for the community focused on lncRNA research in cancer. SIGNIFICANCE: lnCAR, a new interactive tool of reannotated public cancer-related microarray data, provides expression profiles and prognostic landscapes of lncRNAs across thousands of samples and multiple cancer types.
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http://dx.doi.org/10.1158/0008-5472.CAN-18-2169DOI Listing
April 2019

DeepNitro: Prediction of Protein Nitration and Nitrosylation Sites by Deep Learning.

Genomics Proteomics Bioinformatics 2018 08 27;16(4):294-306. Epub 2018 Sep 27.

State Key Laboratory of Oncology in South China, Cancer Center, Collaborative Innovation Center for Cancer Medicine, School of Life Sciences, Sun Yat-sen University, Guangzhou 510060, China. Electronic address:

Protein nitration and nitrosylation are essential post-translational modifications (PTMs) involved in many fundamental cellular processes. Recent studies have revealed that excessive levels of nitration and nitrosylation in some critical proteins are linked to numerous chronic diseases. Therefore, the identification of substrates that undergo such modifications in a site-specific manner is an important research topic in the community and will provide candidates for targeted therapy. In this study, we aimed to develop a computational tool for predicting nitration and nitrosylation sites in proteins. We first constructed four types of encoding features, including positional amino acid distributions, sequence contextual dependencies, physicochemical properties, and position-specific scoring features, to represent the modified residues. Based on these encoding features, we established a predictor called DeepNitro using deep learning methods for predicting protein nitration and nitrosylation. Using n-fold cross-validation, our evaluation shows great AUC values for DeepNitro, 0.65 for tyrosine nitration, 0.80 for tryptophan nitration, and 0.70 for cysteine nitrosylation, respectively, demonstrating the robustness and reliability of our tool. Also, when tested in the independent dataset, DeepNitro is substantially superior to other similar tools with a 7%-42% improvement in the prediction performance. Taken together, the application of deep learning method and novel encoding schemes, especially the position-specific scoring feature, greatly improves the accuracy of nitration and nitrosylation site prediction and may facilitate the prediction of other PTM sites. DeepNitro is implemented in JAVA and PHP and is freely available for academic research at http://deepnitro.renlab.org.
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http://dx.doi.org/10.1016/j.gpb.2018.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205083PMC
August 2018

Pan-Cancer Analysis Reveals the Functional Importance of Protein Lysine Modification in Cancer Development.

Front Genet 2018 17;9:254. Epub 2018 Jul 17.

State Key Laboratory of Oncology in South China, Cancer Center, Collaborative Innovation Center for Cancer Medicine, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.

Large-scale tumor genome sequencing projects have revealed a complex landscape of genomic mutations in multiple cancer types. A major goal of these projects is to characterize somatic mutations and discover cancer drivers, thereby providing important clues to uncover diagnostic or therapeutic targets for clinical treatment. However, distinguishing only a few somatic mutations from the majority of passenger mutations is still a major challenge facing the biological community. Fortunately, combining other functional features with mutations to predict cancer driver genes is an effective approach to solve the above problem. Protein lysine modifications are an important functional feature that regulates the development of cancer. Therefore, in this work, we have systematically analyzed somatic mutations on seven protein lysine modifications and identified several important drivers that are responsible for tumorigenesis. From published literature, we first collected more than 100,000 lysine modification sites for analysis. Another 1 million non-synonymous single nucleotide variants (SNVs) were then downloaded from TCGA and mapped to our collected lysine modification sites. To identify driver proteins that significantly altered lysine modifications, we further developed a hierarchical Bayesian model and applied the Markov Chain Monte Carlo (MCMC) method for testing. Strikingly, the coding sequences of 473 proteins were found to carry a higher mutation rate in lysine modification sites compared to other background regions. Hypergeometric tests also revealed that these gene products were enriched in known cancer drivers. Functional analysis suggested that mutations within the lysine modification regions possessed higher evolutionary conservation and deleteriousness. Furthermore, pathway enrichment showed that mutations on lysine modification sites mainly affected cancer related processes, such as cell cycle and RNA transport. Moreover, clinical studies also suggested that the driver proteins were significantly associated with patient survival, implying an opportunity to use lysine modifications as molecular markers in cancer diagnosis or treatment. By searching within protein-protein interaction networks using a random walk with restart (RWR) algorithm, we further identified a series of potential treatment agents and therapeutic targets for cancer related to lysine modifications. Collectively, this study reveals the functional importance of lysine modifications in cancer development and may benefit the discovery of novel mechanisms for cancer treatment.
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http://dx.doi.org/10.3389/fgene.2018.00254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056651PMC
July 2018

m6ASNP: a tool for annotating genetic variants by m6A function.

Gigascience 2018 05;7(5)

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, China.

Background: Large-scale genome sequencing projects have identified many genetic variants for diverse diseases. A major goal of these projects is to characterize these genetic variants to provide insight into their function and roles in diseases. N6-methyladenosine (m6A) is one of the most abundant RNA modifications in eukaryotes. Recent studies have revealed that aberrant m6A modifications are involved in many diseases.

Findings: In this study, we present a user-friendly web server called "m6ASNP" that is dedicated to the identification of genetic variants that target m6A modification sites. A random forest model was implemented in m6ASNP to predict whether the methylation status of an m6A site is altered by the variants that surround the site. In m6ASNP, genetic variants in a standard variant call format (VCF) are accepted as the input data, and the output includes an interactive table that contains the genetic variants annotated by m6A function. In addition, statistical diagrams and a genome browser are provided to visualize the characteristics and to annotate the genetic variants.

Conclusions: We believe that m6ASNP is a very convenient tool that can be used to boost further functional studies investigating genetic variants. The web server "m6ASNP" is implemented in JAVA and PHP and is freely available at [60].
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http://dx.doi.org/10.1093/gigascience/giy035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007280PMC
May 2018

Large-scale comparative epigenomics reveals hierarchical regulation of non-CG methylation in .

Proc Natl Acad Sci U S A 2018 01 16;115(5):E1069-E1074. Epub 2018 Jan 16.

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095;

Genome-wide characterization by next-generation sequencing has greatly improved our understanding of the landscape of epigenetic modifications. Since 2008, whole-genome bisulfite sequencing (WGBS) has become the gold standard for DNA methylation analysis, and a tremendous amount of WGBS data has been generated by the research community. However, the systematic comparison of DNA methylation profiles to identify regulatory mechanisms has yet to be fully explored. Here we reprocessed the raw data of over 500 publicly available WGBS libraries from various mutant backgrounds, tissue types, and stress treatments and also filtered them based on sequencing depth and efficiency of bisulfite conversion. This enabled us to identify high-confidence differentially methylated regions (hcDMRs) by comparing each test library to over 50 high-quality wild-type controls. We developed statistical and quantitative measurements to analyze the overlapping of DMRs and to cluster libraries based on their effect on DNA methylation. In addition to confirming existing relationships, we revealed unanticipated connections between well-known genes. For instance, MET1 and CMT3 were found to be required for the maintenance of asymmetric CHH methylation at nonoverlapping regions of CMT2 targeted heterochromatin. Our comparative methylome approach has established a framework for extracting biological insights via large-scale comparison of methylomes and can also be adopted for other genomics datasets.
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http://dx.doi.org/10.1073/pnas.1716300115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798360PMC
January 2018

m6AVar: a database of functional variants involved in m6A modification.

Nucleic Acids Res 2018 01;46(D1):D139-D145

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, China.

Identifying disease-causing variants among a large number of single nucleotide variants (SNVs) is still a major challenge. Recently, N6-methyladenosine (m6A) has become a research hotspot because of its critical roles in many fundamental biological processes and a variety of diseases. Therefore, it is important to evaluate the effect of variants on m6A modification, in order to gain a better understanding of them. Here, we report m6AVar (http://m6avar.renlab.org), a comprehensive database of m6A-associated variants that potentially influence m6A modification, which will help to interpret variants by m6A function. The m6A-associated variants were derived from three different m6A sources including miCLIP/PA-m6A-seq experiments (high confidence), MeRIP-Seq experiments (medium confidence) and transcriptome-wide predictions (low confidence). Currently, m6AVar contains 16 132 high, 71 321 medium and 326 915 low confidence level m6A-associated variants. We also integrated the RBP-binding regions, miRNA-targets and splicing sites associated with variants to help users investigate the effect of m6A-associated variants on post-transcriptional regulation. Because it integrates the data from genome-wide association studies (GWAS) and ClinVar, m6AVar is also a useful resource for investigating the relationship between the m6A-associated variants and disease. Overall, m6AVar will serve as a useful resource for annotating variants and identifying disease-causing variants.
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http://dx.doi.org/10.1093/nar/gkx895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5753261PMC
January 2018

VirusMap: A visualization database for the influenza A virus.

J Genet Genomics 2017 05 29;44(5):281-284. Epub 2017 Apr 29.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, China; State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China; Collaborative Innovation Center of High Performance Computing, National University of Defense Technology, Changsha 410073, China. Electronic address:

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http://dx.doi.org/10.1016/j.jgg.2017.04.002DOI Listing
May 2017

The expression of Bcl-6 in circulating follicular helper-like T cells positively correlates with the disease activity in systemic lupus erythematosus.

Clin Immunol 2016 Dec 3;173:161-170. Epub 2016 Nov 3.

Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China. Electronic address:

Increased circulating follicular helper-like T cells (cTfh) are reported in systemic lupus erythematosus (SLE) patients. However, whether B-cell lymphoma 6 (Bcl-6) is expressed in cTfh cells remains to be clarified. In this study, we found that the frequencies of CD4CXCR5PD-1cTfh, CD4CXCR5PD-1ICOS, and CD4CXCR5PD-1Bcl-6 populations were significantly increased in SLE patients (n=70) when compared with healthy controls (n=48). Surprisingly, only CD4CXCR5PD-1Bcl-6 cTfh cells, rather than CD4CXCR5PD-1 population, were positively correlated with SLEDAI and anti-dsDNA antibodies. An elevated level of IL-21 was found in SLE CD4 T cells. Moreover, IL-21 promoted the enrichment of TET2 in Bcl-6 promoter region and induced Bcl-6 expression. Therefore, Bcl-6 expression in cTfh cells may represent a reliable marker for the disease activity in SLE.
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http://dx.doi.org/10.1016/j.clim.2016.10.017DOI Listing
December 2016

GPS-Lipid: a robust tool for the prediction of multiple lipid modification sites.

Sci Rep 2016 06 16;6:28249. Epub 2016 Jun 16.

State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510275, China.

As one of the most common post-translational modifications in eukaryotic cells, lipid modification is an important mechanism for the regulation of variety aspects of protein function. Over the last decades, three classes of lipid modifications have been increasingly studied. The co-regulation of these different lipid modifications is beginning to be noticed. However, due to the lack of integrated bioinformatics resources, the studies of co-regulatory mechanisms are still very limited. In this work, we developed a tool called GPS-Lipid for the prediction of four classes of lipid modifications by integrating the Particle Swarm Optimization with an aging leader and challengers (ALC-PSO) algorithm. GPS-Lipid was proven to be evidently superior to other similar tools. To facilitate the research of lipid modification, we hosted a publicly available web server at http://lipid.biocuckoo.org with not only the implementation of GPS-Lipid, but also an integrative database and visualization tool. We performed a systematic analysis of the co-regulatory mechanism between different lipid modifications with GPS-Lipid. The results demonstrated that the proximal dual-lipid modifications among palmitoylation, myristoylation and prenylation are key mechanism for regulating various protein functions. In conclusion, GPS-lipid is expected to serve as useful resource for the research on lipid modifications, especially on their co-regulation.
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http://dx.doi.org/10.1038/srep28249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910163PMC
June 2016

IBS: an illustrator for the presentation and visualization of biological sequences.

Bioinformatics 2015 Oct 10;31(20):3359-61. Epub 2015 Jun 10.

State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510275, China, Collaborative Innovation Center of High Performance Computing, National University of Defense Technology, Changsha 410073, China, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.

Unlabelled: Biological sequence diagrams are fundamental for visualizing various functional elements in protein or nucleotide sequences that enable a summarization and presentation of existing information as well as means of intuitive new discoveries. Here, we present a software package called illustrator of biological sequences (IBS) that can be used for representing the organization of either protein or nucleotide sequences in a convenient, efficient and precise manner. Multiple options are provided in IBS, and biological sequences can be manipulated, recolored or rescaled in a user-defined mode. Also, the final representational artwork can be directly exported into a publication-quality figure.

Availability And Implementation: The standalone package of IBS was implemented in JAVA, while the online service was implemented in HTML5 and JavaScript. Both the standalone package and online service are freely available at http://ibs.biocuckoo.org.

Contact: renjian.sysu@gmail.com or xueyu@hust.edu.cn

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btv362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4595897PMC
October 2015

An integrated overview of spatiotemporal organization and regulation in mitosis in terms of the proteins in the functional supercomplexes.

Front Microbiol 2014 29;5:573. Epub 2014 Oct 29.

Cancer Center, School of Life Sciences, School of Advanced Computing, Cooperative Innovation Center for High Performance Computing, Sun Yat-sen University Guangzhou, China.

Eukaryotic cells may divide via the critical cellular process of cell division/mitosis, resulting in two daughter cells with the same genetic information. A large number of dedicated proteins are involved in this process and spatiotemporally assembled into three distinct super-complex structures/organelles, including the centrosome/spindle pole body, kinetochore/centromere and cleavage furrow/midbody/bud neck, so as to precisely modulate the cell division/mitosis events of chromosome alignment, chromosome segregation and cytokinesis in an orderly fashion. In recent years, many efforts have been made to identify the protein components and architecture of these subcellular organelles, aiming to uncover the organelle assembly pathways, determine the molecular mechanisms underlying the organelle functions, and thereby provide new therapeutic strategies for a variety of diseases. However, the organelles are highly dynamic structures, making it difficult to identify the entire components. Here, we review the current knowledge of the identified protein components governing the organization and functioning of organelles, especially in human and yeast cells, and discuss the multi-localized protein components mediating the communication between organelles during cell division.
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http://dx.doi.org/10.3389/fmicb.2014.00573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4212687PMC
November 2014

GPS-SUMO: a tool for the prediction of sumoylation sites and SUMO-interaction motifs.

Nucleic Acids Res 2014 Jul 31;42(Web Server issue):W325-30. Epub 2014 May 31.

State Key Laboratory of Biocontrol, School of Life Sciences, School of Advanced Computing, Sun Yat-sen University, Guangzhou 510275, China

Small ubiquitin-like modifiers (SUMOs) regulate a variety of cellular processes through two distinct mechanisms, including covalent sumoylation and non-covalent SUMO interaction. The complexity of SUMO regulations has greatly hampered the large-scale identification of SUMO substrates or interaction partners on a proteome-wide level. In this work, we developed a new tool called GPS-SUMO for the prediction of both sumoylation sites and SUMO-interaction motifs (SIMs) in proteins. To obtain an accurate performance, a new generation group-based prediction system (GPS) algorithm integrated with Particle Swarm Optimization approach was applied. By critical evaluation and comparison, GPS-SUMO was demonstrated to be substantially superior against other existing tools and methods. With the help of GPS-SUMO, it is now possible to further investigate the relationship between sumoylation and SUMO interaction processes. A web service of GPS-SUMO was implemented in PHP+JavaScript and freely available at http://sumosp.biocuckoo.org.
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http://dx.doi.org/10.1093/nar/gku383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4086084PMC
July 2014

HLA-A, -B, and -DRB1 gene polymorphism in the Miao ethnic group of Hunan, China.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2010 Apr;35(4):277-85

Graduate School of Chinese Academy of Sciences, Beijing 100049, China.

Objective: To investigate HLA-A, -B, and -DRB1 gene polymorphism in the Miao ethnic group in Hunan, China.

Methods: PCR-sequence specific oligonucleotide probes (SSO) reverse flow chip method was used to type HLA-A, -B, and -DRB1 genes of 154 unrelated healthy Miao ethnic individuals in Hunan. The allele and haplotype frequencies were calculated and compared with other populations in China.

Results: A total of 10 HLA-A, 25 HLA-B, and 13 HLA-DRB1 alleles were observed in the population. The higher frequency alleles included A 11(38.96%), A 02(27.27%), A 24(18.83%), B 40(60)(17.53%), B 46(13.96%), B 15(75)(11.69%), DRB1 09(15.26%), DRB1 12(15.26%), DRB1 15(15.26%), and DRB1 04(12.66%). The most frequent haplotypes were A11-B60(9.60%), A2-B46(9.27%), A11-B75(9.22%), B75-DR12(6.31%), A11-DR12(9.62%), A11-DR4(9.07%), A11-DR15(6.69%), A11-B75-DR12(5.43%), A11-B60-DR4(4.24%), and A2-B46-DR9(3.71%). Compared with other populations in China, HLA gene polymorphism of Hunan Miao population was close to that of southern population.

Conclusion: HLA loci are highly polymorphic in the Miao population of Hunan, and their distribution has the character of South China population.
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http://dx.doi.org/10.3969/j.issn.1672-7347.2010.04.001DOI Listing
April 2010