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DeepCAGE:Incorporating Transcription Factors in Genome-wide Prediction of Chromatin Accessibility

Genomics, Proteomics & bioinformatics 2022年第3期20卷 496-507页

作者： Qiao Liu Kui Hua Xuegong Zhang Wing Hung Wong Rui Jiang Ministry of Education Key Laboratory of bioinformatics Bioinformatics DivisionBeijing National Research Center for Information Science and TechnologyCenter for Synthetic and Systems BiologyDepartment of AutomationTsinghua UniversityBeijing 100084China Department of Statistics Stanford UniversityStanfordCA 94305USA

Although computational approaches have been complementing high-throughput biological experiments for the identification of functional regions in the human genome,it remains a great challenge to systematically decipher interactions between transcription factors(TFs)and regulatory elements to achieve interpretable annotations of chromatin accessibility across diverse cellular *** solve this problem,we propose DeepCAGE,a deep learning framework that integrates sequence information and binding statuses of TFs,for the accurate prediction of chromatin accessible regions at a genome-wide scale in a variety of cell *** takes advantage of a densely connected deep convolutional neural network architecture to automatically learn sequence signatures of known chromatin accessible regions and then incorporates such features with expression levels and binding activities of human core TFs to predict novel chromatin accessible *** a series of systematic comparisons with existing methods,DeepCAGE exhibits superior performance in not only the classification but also the regression of chromatin accessibility *** a detailed analysis of TF activities,DeepCAGE successfully extracts novel binding motifs and measures the contribution of a TF to the regulation with respect to a specific locus in a certain cell *** applied to whole-genome sequencing data analysis,our method successfully prioritizes putative deleterious variants underlying a human complex trait and thus provides insights into the understanding of disease-associated genetic *** can be downloaded from https://***/kimmo1019/DeepCAGE.

关键词： Chromatin accessibility Deep learning Transcription factor Gene expression

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Determination of barbiturates in hair samples by using a validated UHPLC-HRMS method: application in investigation of drug-facilitated sexual assault

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Forensic Sciences Research 2022年第1期7卷 78-87页

作者： Di Wen Yan Shi Xiaoguang Zhang Bing Xie Wenqiao Liu Feng Yu Ping Xiang Bin Cong Chunling Ma College of Forensic Medicine Hebei Medical UniversityHebei Key Laboratory of Forensic MedicineCollaborative Innovation Center of Forensic Medical Molecular IdentificationShijiazhuangChina Academy of Forensic Science Ministry of JusticeShanghai Key Laboratory of Forensic MedicineShanghaiChina core facility of Hebei Medical University ShijiazhuangChina

In recent years,benzodiazepines and benzodiazepine-like drugs are the most common substances associated with drug-facilitated sexual assaults(DFSA);however,barbiturates are also detected *** hair analysis provides useful information on the historic pattern of drug use,enabling differentiation between single exposure in DFSA cases and chronic ***,sensitive and specific methods for barbiturate analysis in hair samples are ***,we present an ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry(UHPLC-HRMS)method for qualitative and quantitative determination of seven barbiturates in hair ***,a hair strand was decontaminated and then freeze-milled in liquid ***,50mg of powdered hair was extracted with methanol in an ultrasonic bath for 10 min in the presence of 10 ng *** supernatant was dried under nitrogen gas,and the pellet was dissolved in 100 μL mobile ***,10 μL of the suspension was injected into the UHPLC-HRMS *** present method involved two UHPLC conditions for determination of barbiturates(I)and identification of the structural isomers amobarbital and pentobarbital(II).This method showed satisfactory linearity in a range of 0.02–20.00 ng/mg for UHPLC conditions I and II,both with a high determination coefficient(0.9991–0.9999).The selectivity,intra-and interday precision,accuracy and matrix effect of the method were ***,the validated method was applied to investigate an authentic DFSA *** samples(black,approximate 25cm long)were collected 3 months after the assault,and the proximal segments(0–5 cm from the root;each segment was 1 cm long)were *** was detected at a concentration of

关键词： Forensic sciences forensic toxicology segmental hair analysis barbiturates UHPLC-HRMS drugfacilitated sexual assault

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Toll-like receptor 10 (TLR10) exhibits suppressive effects on inflammation of prostate epithelial cells

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Asian Journal of Andrology 2019年第4期21卷 393-399页

作者： Yu Fan Lu Yang Qiang Wei Yu Ding Zhuang Tang Ping Tan Tao Lin Duan Guo Shi Qiu Department of Urology Institute of Urology West China Hospital of Sichuan University Chengdu 610041 China Department of core facility West China Hospital of Sichuan University Chengdu 610041 China Department of Urology Sun Yat-Sen Memorial Hospital of Zhongshan University Guangzhou 510120 China Department of Palliative Medicine West China Fourth Affiliated Hospital of Sichuan University Chengdu 610041 China

Prostate inflammation (PI) is closely related to the development and progression of chronic prostatic diseases: benign prostatic hyperplasia and prostate cancer. Toll-like receptor (TLR) 2 has been reported to be associated with inflammatory diseases, such as infections, autoimmune diseases, and cancers. Meanwhile, TLR10, which can form heterodimers with TLR2, has been considered an orphan receptor without an exact function. The present study therefore aims to examine the effects of TLR2 and TLR10 on PI. Prostate samples and clinical data were obtained from the patients diagnosed with benign prostatic hyperplasia. The inflammatory cell model was established by adding lipopolysaccharide to RWPE-1 cells. Prostate tissues/cells were examined by histological, molecular, and biochemical approaches. Both TLR2 and TLR10 were found to be expressed in prostate tissues and RWPE-1 cells. mRNA/protein expression levels of TLR2 and TLR10 were both positively correlated with prostate tissue inflammatory grades. Lipopolysaccharide-stimulated RWPE-1 cells expressed higher levels of TLR2, TLR10, high mobility group box 1 (HMGB1), phosphonuclear factor kappa-light-chain-enhancer of activated B-cells P65 (phospho-NF-κB P65), interleukin (IL)-6, and IL-8 than control cells. Moreover, HMGB1, phospho-NF-κB P65, IL-6, and IL-8 were down regulated after TLR2 knockdown and upregulated after TLR10 knockdown in RWPE-1 cells. TLR2 stimulation can activate the inflammatory signaling cascade in prostate epithelial cells. Conversely, TLR10 exhibited suppressive effects on inflammation. With antagonistic functions, both TLR2 and TLR10 were invoIved in PI. TLR10 could be a novel target in modulating inflammatory signal transduction of prostate epithelial cells.

关键词： benign prostatic hyperplasia inflammation Toll-like receptor 2 (TLR2) TLR10

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In silico docking analysis of beta-defensin 20 against cation channel sperm-associated protein 1–4 to predict its role in the sperm maturation

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Asian Journal of Andrology 2023年第4期25卷 528-532页

作者： Luluk Yunaini Linda Erlina Fadilah Fadilah Dwi Ari Pujianto Doctoral Program for Biomedical Sciences Faculty of MedicineUniversitas IndonesiaJakarta 10430Indonesia Department of Medical Biology Faculty of MedicineUniversitas IndonesiaJakarta 10430Indonesia Department of Medical Chemistry Faculty of MedicineUniversitas IndonesiaJakarta 10430Indonesia bioinformatics core Facilities Indonesia Medical Education and Research Institute(IMERI)Faculty of MedicineUniversitas IndonesiaJakarta 10430Indonesia

Beta-defensin 20(DEFB20)is widely expressed in the epididymis with gene features involved in epididymal sperm ***,the action mechanism and function of DEFB20 in sperm maturation are still *** of the important roles of beta-defensin is the ion channel *** cation channel sperm-associated protein(CatSper)alpha is an ion channel protein found on the sperm *** study aimed to investigate the interaction between DEFB20 and CatSper1–4 protein in relation to the sperm maturation *** sequences were obtained from the National Center for Biotechnology Information(NCBI).Protein modeling and validation were carried out by using the Robetta modeling server and the Ramachandran plot *** web server was used for the docking *** results revealed a natural interaction between DEFB20 and CatSper1–*** interaction occurred at the cation channel(close to the casein kinase II),ion transport protein,and kinase c phosphorylation of the CatSper1–4 active *** DEFB20 region interacting with CatSper2–4 was the beta-defensin domain,while with CatSper1 was the non-beta-defensin *** on the analysis,DEFB20 may interact with CatSperαsubunits,particularly CatsSper1,to affect ion channel activity during sperm maturation.

关键词： CatSper DEFB20 docking sperm maturation

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Implementation of Automated Sample Quality Control in Whole Exome Sequencing

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Journal of Life Sciences 2017年第6期11卷 261-268页

作者： Elisa Viering Jana Molitor Leslie Friedmann Jana Petersen Marie Beckhaus Stephan Wolf Agilent Technologies Inc. Waldbronn 76337 Germany DKFZ Genomics and Proteomics core facility High Throughput Sequencing Unit Heidelberg 69120 Germany

Aims： High-quality DNA as input material for a NGS （next-generation sequencing） workflow is essential for the successful preparation of a DNA library. Additionally, DNA quality has a strong impact on sequencing results. Therefore, it is important to include QC （quality control） steps to assess size, concentration, molarity, and integrity of the DNA during the workflow. Material and Methods： The WES （Whole Exome Sequencing） workflow at the Genomics and Proteomics core facility of DKFZ （the German Cancer Research Center） was performed with several QC steps： QC of the input material, QC of intermediate products during library preparation, and QC of final libraries. The Agilent 4200 TapeStation system, which offers automated sample processing, was used to evaluate quantity, size, molarity, and integrity of the samples. Key Findings： The Agilent Genomic DNA ScreenTape assay offers an unbiased genomic DNA integrity assessment, which enables protocol adaption for optimized library preparation, for example, selection of a suitable shearing protocol. Additionally, QC steps during library preparation such as evaluation of library size, concentration, and molarity ensure maximal sequencing output. Significance： The automated and fast high-throughput analysis of genomic DNA with the 4200 TapeStation system helps to save labor time and costs. Additionally, the easy-to-use system can be integrated as a QC tool into the NGS workflow to ensure successful library preparation. QC steps enable the confirmation of suitable library size and concentration for the workflow.

关键词： NGS FFPE (Formalin-fixed Paraffin-embedded) WES DIN (DNA Integrity Number) QC 4200 TapeStation system.

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Pulmonary tumor thrombotic microangiopathy of hepatocellular carcinoma: A case report and review of literature

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World Journal of Gastroenterology 2019年第48期25卷 6949-6958页

作者： Shinichi Morita Kenya Kamimura Hiroyuki Abe Yukari Watanabe-Mori Chiyumi Oda Takamasa Kobayashi Yoshihisa Arao Yusuke Tani Riuko Ohashi Yoichi Ajioka Shuji Terai Division of Gastroenterology and Hepatology Graduate School of Medical and Dental SciencesNiigata UniversityNiigata 951-8510Japan Division of Molecular and Diagnostic Pathology Niigata University Graduate School of Medical and Dental SciencesNiigata UniversityNiigata 951-8510Japan Histopathology core facility Niigata University Faculty of MedicineNiigata UniversityNiigata 951-8510Japan

BACKGROUND Pulmonary tumor thrombotic microangiopathy(PTTM)is a rare condition in patients with hepatocellular carcinoma(HCC);to date,few cases have been *** hepatic dysfunction has been focused on the later stages of HCC,the management of symptoms in PTTM is important for supportive care of the *** the better understanding of PTTM in HCC,the information of our recent case and reported cases have been *** SUMMARY A patient with HCC exhibited acute and severe respiratory *** and computed tomography of the chest revealed the multiple metastatic tumors and a frosted glass–like shadow with no evidence of infectious *** diagnosed his condition as acute respiratory distress syndrome caused by the lung metastases and involvement of the pulmonary vessels by tumor *** of prednisolone to alleviate the diffuse alveolar damages including edematous changes of alveolar wall caused by the tumor cell infiltration and ischemia showed mild improvement in his symptoms and imaging *** autopsy showed the typical pattern of PTTM in the lung with multiple *** PTTM is caused by tumor thrombi in the arteries and thickening of the pulmonary arterial endothelium leading to the symptoms of dyspnea in terminal staged ***,supportive management of symptoms is necessary in the cases with PTTM and hence we believe that the information presented here is of great significance for the diagnosis and management of symptoms of PTTM with HCC.

关键词： Pulmonary tumor thrombotic microangiopathy Hepatocellular carcinoma Respiratory dysfunction Prednisolone Supportive care Case report

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ModuleNet:An R package on regulatory network building

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Chinese Science Bulletin 2010年第30期55卷 3430-3435页

作者： ZHOU Dao HE Dong LUO QingMing ZHOU YanHong Hubei Key Laboratory of bioinformatics and Molecular Imaging Huazhong University of Science and Technology Wuhan 430074 China

Many researchers have used microarray gene expression data to investigate gene regulatory networks in specific life stages. In these analyses,Bayesian network was widely applied to regulatory network building from expression profiles because of its solid mathematical foundation and its robust analysis ability in noisy data. However,the building of Bayesian network is time consuming and the searching space is really large. Considering the biological feature of transcription factors (TFs) and targets (TGs),the regulatory network is possible to be separated into core TFs networks and the interactions from TFs to TGs. We developed an R package named ModuleNet which used Bayesian network model to the inner TFs network building and genetic algorithm on TF-TG interactions prediction. With determined number of transcription factors,the searching space and time requirements of ModuleNet is linear increasing according to the number of targets. After application to yeast cell-cycle expression profile,the results demonstrated the prediction accuracy of ModuleNet. Furthermore,significantly enriched Gene Ontology (GO) terms with similar expression behaviors were detected automatically by ModuleNet from expression profile,and the relationships from TFs to GO terms were figured out. The source code is available by asking for the author.

关键词：网络建设监管贝叶斯网络模型基因表达数据基因表达谱转录因子封装基因调控网络

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Childhood overweight and risk of obesity-related adult cancer in men

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Cancer Communications 2022年第6期42卷 576-579页

作者： Jimmy Célind Maria Bygdell Jari Martikainen Claes Ohlsson Jenny M Kindblom Sahlgrenska Osteoporosis Centre Centre for Bone and Arthritis ResearchInstitute of MedicineSahlgrenska Academy at University of GothenburgGothenburgVastra Gotaland41345Sweden Department of Pediatrics Institute of Clinical SciencesThe Sahlgrenska Academy at University of GothenburgGothenburgVastra Gotaland41124Sweden bioinformatics core facility Sahlgrenska AcademyUniversity of GothenburgGothenburgVastra Gotaland41124Sweden Department of Drug Treatment Sahlgrenska University HospitalRegion Vastra GotalandGothenburg 41345Sweden Pediatric Clinical Research Center Sahlgrenska University HospitalRegion Vastra GotalandGothenburg 41345Sweden

Dear Editor,The global burden of cancer is *** list of malignancies regarded as obesity-related continues to expand as evidence accumulates[1,2].Fueled by the ongoing obesity epidemic,obesity has emerged as one of the most important preventable causes of cancerworldwide[1,3].Given the long latency periods of many obesity-related adult cancers,risk factors with onset during early age and accumulation of risks during one’s life course are likely to be of importance[4].

关键词： obesity cancer likely

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Automated Detection and Quantification of Prostate Cancer in Needle Biopsies by Digital Image Analysis

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Open Journal of Pathology 2014年第3期4卷 138-150页

作者： Vamsi Parimi Laurie J. Eisengart Ximing J. Yang Department of Pathology Northwestern University Chicago IL USA Pathology core facility Robert H. Lurie Comprehensive Cancer Center Chicago IL USA

Introduction: Triple immunohistochemical (IHC) stains including antibodies specific for alpha-methylacyl-CoA-racemase and basal cell markers have been a valuable aid in accurate identification of prostate carcinoma. However, accurate quantification of minuscule areas of prostate carcinoma in biopsy specimens can often be a challenge. Here we assessed the diagnostic value and quantitative use of automated digital image analysis on triple IHC stained prostate needle biopsies. Methods: Twelve cases of prostate needle biopsy material including 75 needle cores were stained with triple-antibody cocktail (P504S + 34βE12 + p63). Slides were digitally scanned with the APERIO digital image analyzer and evaluated with the GENIE pattern and color recognition digital image analysis that we developed. A slide with known areas of adenocarcinoma, high grade prostatic intraepithelial neoplasia (PIN), benign glands and stroma was used as a training set for the automated digital image analysis platform. Results: Among 75 needle biopsy cores, 19 (25.33%) contained adenocarcinoma by histology. Digital image analysis recognized adenocarcinoma in 95% of these needle biopsies. The average area of the needle biopsy was 7.63 mm2 and overall the average area of tumor was 0.196 mm2. The smallest area of tumor recognized by the program was 0.0022 mm2 (0.0363% of the core) and the largest was 0.62 mm2 (8.17% of the core) among needle core biopsies. False positives resulted from areas of high grade PIN with patchy basal cells. The false negative was caused by uneven AMACR staining in one area of adenocarcinoma. Digital recognition of areas of interest was improved by three successive image analysis training which increased the sensitivity and specificity from 83% and 89% to 90% and 93%, respectively. Conclusions: Digital image analysis in concert with IHC triple staining may be useful for accurate detection and quantitative analysis of small foci of prostatic adenocarcinoma. Defining methods to i

关键词： Prostatic Adenocarcinoma Needle Biopsy Alpha-Methylacyl-CoA-Racemase P504S Basal Cell Immunohistochemistry Automated Digital Image Analysis

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Patterns of Chromatin-Modifications Discriminate Different Genomic Features in Arabidopsis

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Tsinghua Science and Technology 2013年第5期18卷 431-440页

作者： Anuj Srivastava Xiaoyu Zhang Sal LaMarca Liming Cai Russell L. Malmberg Institute of bioinformatics University of Georgia The Jackson Laboratory Department of Plant Biology University of Georgia Department of Computer Science University of Georgia

Dynamic regulation and packaging of genetic information is achieved by the organization of DNA into chromatin. Nucleosomal core histones, which form the basic repeating unit of chromatin, are subject to various post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitinylation. These modifications have effects on chromatin structure and, along with DNA methylation, regulate gene *** goal of this study was to determine if patterns in modifications were related to different categories of genomic features, and, if so, if the patterns had predictive value. In this study, we used publically available data（ChIP-chip）for different types of histone modifications（methylation and acetylation） and for DNA methylation for Arabidopsis thaliana and then applied a machine learning based approach（a support vector machine） to demonstrate that patterns of these modifications are very different among different kinds of genomic feature categories（protein, RNA,pseudogene, and transposon elements）. These patterns can be used to distinguish the types of genomic *** methylation and H3K4me3 methylation emerged as features with most discriminative power. From our analysis on Arabidopsis, we were able to predict 33 novel genomic features, whose existence was also supported by analysis of RNA-seq experiments. In summary, we present a novel approach which can be used to discriminate/detect different categories of genomic features based upon their patterns of chromatin modification and DNA methylation.

关键词： chromatin modification DNA methylation support vector machine machine learning Arabidopsis

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