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International Computer Science and Engineering Conference (ICSEC)

作者： Songtham Anuntakarun Warin Wattanapornprom Supatcha Lertampaiporn Bioinformatics and Systems Biology Program King Mongkut’s University of Technology Thonburi Bangkok Thailand Department of Mathematics University of Technology Thonburi Bangkok Thailand Biochemical Engineering and Systems Biology Research Group National Center for Genetic Engineering and Biotechnology (BIOTEC) King Mongkut’s University of Technology Thonburi Bangkok Thailand

In this work, preliminary experiments of using diverse machine learning algorithms and testing of multiple relevant features to discriminate between human lncRNAs and coding/partial coding sequences was performed. This research limited the size of human lncRNAs such that they are shorter than 1000 nucleotides. Various significant features in describing RNA sequence including sequenced based features, secondary structure features, base-pair features and structural robustness features were used in this study. Then, the top 20 significant features were selected using Wilcoxon rank-sum test and discovered that the secondary structure features are the unique characteristics for identifying the human lncRNAs which are quite difference with those in the groups of shorter and longer types of ncRNAs. Such features are suitable with the rule-based classifiers like Random Forest. According to 10-folding cross validation, the random forest model has shown the highest accuracy, sensitivity and specificity as well as the lowest false positive rate among all competitors. Furthermore, the model was compared with other state-of -the-art approaches such as CPC, CPAT, RNAcon and achieved the highest accuracy of 84.5% among all the participants.

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ASpli: Integrative analysis of splicing landscapes through RNA-Seq assays (Mar, btab141, 2021)

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bioinformatics 2021年第12期37卷 1783-1783页

作者： Mancini, Estefania Rabinovich, Andres Iserte, Javier Yanovsky, Marcelo Chernomoretz, Ariel Gene Regulation Stem Cells and Cancer Program Centre for Genomic Regulation (CRG) The Barcelona Institute of Science and Technology Barcelona Spain. Integrative Systems Biology Fundacion Instituto Leloir Buenos Aires Argentina. Instituto de Investigaciones Bioquímicas de Buenos Aires Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) Buenos Aires Argentina. DStructural Bioinformatics Fundacion Instituto Leloir Buenos Aires Argentina. Comparative Genomics of Plant Development Fundacion Instituto Leloir Buenos Aires Argentina.

MOTIVATION:Genome-wide analysis of alternative splicing has been a very active field of research since the early days of next generation sequencing technologies. Since then, ever-growing data availability and the development of increasingly sophisticated analysis methods have uncovered the complexity of the general splicing repertoire. A large number of splicing analysis methodologies exist, each of them presenting its own strengths and weaknesses. For instance, methods exclusively relying on junction information do not take advantage of the large majority of reads produced in an RNA-seq assay, isoform reconstruction methods might not detect novel intron retention events, some solutions can only handle canonical splicing events, and many existing methods can only perform pairwise comparisons. RESULTS:In this contribution, we present ASpli, a computational suite implemented in R statistical language, that allows the identification of changes in both, annotated and novel alternative-splicing events and can deal with simple, multi-factor or paired experimental designs. Our integrative computational workflow, that considers the same GLM model applied to different sets of reads and junctions, allows computation of complementary splicing signals. Analyzing simulated and real data, we found that the consolidation of these signals resulted in a robust proxy of the occurrence of splicing alterations. While the analysis of junctions allowed us to uncover annotated as well as non-annotated events, read coverage signals notably increased recall capabilities at a very competitive performance when compared against other state-of-the-art splicing analysis algorithms. AVAILABILITY AND IMPLEMENTATION:ASpli is freely available from the Bioconductor project site https://***/doi:10.18129/***. SUPPLEMENTARY INFORMATION:Supplementary data are available at bioinformatics online.

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A systems biology Approach to Investigate Control Targets of Intracellular Calcium Transients Induced by Clostridium Perfringens Phospholipase C

A Systems Biology Approach to Investigate Control Targets of...

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International Work Conference on Bio-inspired Intelligence (IWOBI)

作者： Laura Brenes-Guillén Man-Sai Acón-Chan Rodrigo Mora-Rodríguez Laura Monturiol-Gross Celular and Molecular Biology University of Costa Rica (UCR) San José Costa Rica Master Program on Bioinformatics and Systems Biology University of Costa Rica (UCR) San José Costa Rica Faculty of Microbiology University of Costa Rica (UCR) San José Costa Rica

Clostridium perfringens phospholipase C (CpPLC) plays a key role in the pathogenesis of gas gangrene, an acute and life-threatening infection in humans. CpPLC leads to the unregulated production of second messengers, such as calcium, and activates important signaling pathways like PKC, MEK, and NFkB, inducing ROS production, that leads towards cellular damage. We propose a systems biology approach to identify potential microRNAs which could be used as tools to explore the role of calcium channels in the mechanism of action of CpPLC, and eventually as therapeutic agents that render cells less sensitive to this toxin. Results show that miR19B1 and miR449B are interesting candidate targets which perturbations may affect the expression of genes involved in calcium transport. This approach may be useful to elucidate calcium molecular interactions involved in the CpPLC mechanism of action.

关键词： Calcium Mathematical model Gene expression Network topology Data models systems biology Parameter estimation

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FaNDOM: Fast Nested Distance-Based Seeding of Optical Maps

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SSRN 2021年

作者： Dehkordi, Siavash Raeisi Luebeck, Jens Bafna, Vineet Department of Computer Science & Engineering University of California San Diego San diegoCA92093 United States Bioinformatics & Systems Biology Graduate Program University of California San Diego San diegoCA92093 United States

Optical mapping provides single-molecule readouts of the locations of fluorescently labeled sequence motifs on long fragments of DNA, resolved to nucleotide-level coordinates. With the advent of microfluidic technologies for manipulating large numbers of individual molecules, and advances in the imaging of fluorescent DNA tags, it is possible to inexpensively generate high coverage and long OM molecules (>150Kbp). In addition to its use in scaffolding for de novo assembly, optical map data can also be mapped to a reference for identifying genetic structural variants implicated in Mendelian diseases and cancer. To address the computational challenge, we introduce FaNDOM (Fast Nested Distance seeding of Optical Maps) - an optical map alignment tool which greatly reduces the search space of the alignment process. On 4 benchmark human data-sets, FaNDOM was significantly (4-14X) faster than competing tools while maintaining comparable sensitivity and specificity. We used FaNDOM to map variants in 3 cancer cell-lines and identified many structural variations, including deletion of tumor-suppressor genes, duplications, gene fusions and gene-disrupting rearrangements. FaNDOM is publicly available at (https://***/jluebeck/FaNDOM). © 2021, The Authors. All rights reserved.

关键词： Genes

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Construction and validation of a mouse model for studying severe human adenovirus infections

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Virologica Sinica 2024年第6期39卷 963-973页

作者： Dingbin Chen Yuqian Yan Ting Mei Peipei Yang Siqi Deng Yiqiang Li Tie Zhao Ning Xin Biyan Duan Weifeng Liang Yuemei Yang Wei Zhao Donald Seto Junxian Ou Qiwei Zhang Institute of Medical Microbiology Department of Immunology and MicrobiologyCollege of Life Science and TechnologyJinan UniversityGuangzhou510632China BSL-3 Laboratory(Guangdong) Guangdong Provincial Key Laboratory of Tropical Disease ResearchSchool of Public HealthSouthern Medical UniversityGuangzhou510515China Department of Clinical Laboratory Guangzhou Women and Children's Medical CenterGuangzhou Medical UniversityGuangzhou510620China South Yunnan Central Hospital(Honghe First People's Hospital) MengziYunnan661100China Bioinformatics and Computational Biology Program School of Systems BiologyGeorge Mason UniversityManassasVA20110USA The Affiliated Guangdong Second Provincial General Hospital of Jinan University Guangzhou510310China Key Laboratory of Viral Pathogenesis&Infection Prevention and Control(Jinan University) Ministry of EducationGuangzhou510632China

Human adenoviruses(HAdVs)are highly contagious pathogens with various genotypes implicated in acute respiratory disease(ARD)and linked to fatality,especially in immunosuppressed patients,young children,and military ***,no vaccines or specific drugs are approved for clinical *** hosts of adenoviruses are strictly species-specific,which strongly limits the development of vaccines and drugs against *** this study,immunocompetent BALB/c mice were challenged with different doses of human adenovirus type 5(HAdV-5)via tail intravenous injection(i.v.).All mice challenged with a high dose of HAdV-5(3.21010 TCID50/kg)died within 3–5 days,while those receiving a low dose of HAdV-5(8109 or 4109 TCID50/kg)***,among the mice receiving a medium dose of HAdV-5(1.61010 TCID50/kg),60%(n¼3/5)of male mice died,while all female mice *** suggests that male mice may be more susceptible to HAdV-5 infection than female mice,consistent with clinical findings in ***-5 DNA was mainly distributed in the liver,followed by the spleen and *** changes were observed in the lung,liver,and spleen,with severity increasing in correlation with the virus challenge *** and qPCR analyses of the liver indicated that the down-regulated expression of the H2-Aa,H2-Ea-ps,CD74,and H2-Eb1 genes in male mice,as well as the AHR gene in female mice,may contribute to the observed higher mortality rates in male ***,this effective,feasible,and costefficient mouse model could serve as a candidate for evaluating HAdV vaccines and anti-adenovirus therapeutics.

关键词： Human adenovirus type 5(HAdV-5) Animal model BALB/c mice Severe human adenovirus infections

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Transcriptional Regulatory Network of Arabidopsis Starch Metabolism under Extensive Light Condition: A Potential Model of Transcription-modulated Starch Metabolism in Roots of Starchy Crops

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Procedia Computer Science 2013年 23卷 113-121页

作者： Somkid Bumee Papapit Ingkasuwan Saowalak Kalapanulak Asawin Meechai Supapon Cheevadhanarak Treenut Saithong Systems Biology and Bioinformatics Research Laboratory Pilot Plant Development and Training Institute King Mongkut's University of Technology Thonburi Bangkhuntien campus Bangkok Thailand 10150 Bioinformatics and Systems Biology Program School of Bioresources and Technology King Mongkut's University of Technology Thonburi Bangkhuntien campus Bangkok Thailand 10150 Department of Chemical Engineering Faculty of Engineering King Mongkut's University of Technology Thonburi Bangkok Thailand 10140 Division of Biotechnology School of Bioresources and Technology King Mongkut's University of Technology Thonburi Bangkhuntien campus Bangkok Thailand 10150

Starchy root crops are a major carbohydrates source for being both human food and animal feed. The increasing demand of such crops has been a driving force of studies and research in biology of the crops. However, the related-knowledge as well as the existing information is still very few in comparison with the Arabidopsis model plant. Accordingly, the aims of this work are (1) to attempt to exploit the enormous data of Arabidopsis model plant to infer the regulation in the starchy root crops, and (2) to investigate the possibility and plausibility of the inference. Here, the transcriptional regulatory network of starch metabolism of Arabidopsis under extensive light condition was performed through the modified graphical Gaussian model (GGM) to infer the regulation of the similar process in root crops. The resulting correlation network of the significant genes includes 70 transcription factors and two starch-related genes, alpha-Glucosidase-like3 ( AGL3:At3g45940 ) and beta-Amylase 5 ( BAM5:At4g15210 ). Though the results provided the potential transcription factors of starch-related genes, which could be useful for further investigation, it is more likely that the selected condition of data is not appropriate to represent the starch metabolism in root crops. The results showed that greater than 70% of the significant genes were related to the starch degradation process which might reflect that the plants were under stress. This observation was supported by the Gene Ontology (GO) enrichment analysis that found many enriched GO terms relevant to the stress response. In conclusion, we believe that the data of the model plant are useful for gaining more understanding into the regulation in other plants, including root crops, but the suitable condition of data measurement in use need to be well defined.

关键词： transcriptional regulatory network graphical Gaussian model starch metabolism

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Reconstructing the Lineage Histories and Differentiation Trajectories of Individual Hematopoietic Stem Cells in JAK2-Mutant Myeloproliferative Neoplasms

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BLOOD 2020年 136卷 7-8页

作者： Van Egeren, Debra Escabi, Javier Nguyen, Maximilian Liu, Shichen Reilly, Christopher R. Patel, Sachin Kamaz, Baransel Kalyva, Maria DeAngelo, Daniel J. Galinsky, Ilene Wadleigh, Martha Winer, Eric S. Luskin, Marlise R. Stone, Richard M. Garcia, Jacqueline S. Hobbs, Gabriela S. Camargo, Fernando D. Michor, Franziska Mullally, Ann Cortes-Ciriano, Isidro Hormoz, Sahand Department of Systems Biology Harvard Medical School Boston Princeton University Princeton Department of Biostatistics and Computational Biology Dana-Farber Cancer Institute Boston Department of Medical Oncology Dana-Farber Cancer Institute Boston Hematology/Oncology Department and Stem Cell Program Boston Children's Hospital Boston Division of Hematology Brigham and Women's Hospital Boston European Bioinformatics Institute Cambridge United Kingdom Department of Medical Oncology Dana-Farber Cancer Inst. Boston MA Department of Medical Oncology Dana-Farber Cancer Institute Boston MA Leukemia Center Massachusetts General Hospital Boston MA

*equal contribution, # co-corresponding authors Although the JAK2V617F mutation is the most common MPN phenotypic driver mutation, the precise consequences of the mutation on the behavior of individual human hematopoietic stem cells (HSCs) in vivo remains unknown. We used whole genome sequencing and single-cell profiling of hematopoietic stem and progenitor cells (HSPCs) to quantify the impact of JAK2V617F on the proliferation dynamics of HSCs and the differentiation trajectories of their progenies in individual newly diagnosed MPN patients. We reconstructed the lineage history of individual HSCs obtained from patients with newly diagnosed essential thrombocythemia (ET), using the pattern of spontaneous somatic mutations accrued in their genomes over decades (Figure 1). Intriguingly, our analysis indicates that the JAK2V617F mutation occurred in a single HSC many years before MPN diagnosis - at age 9±2 years in a 34 year-old patient, and at age 19±3 years in a 63 year-old patient. In each patient, we inferred the number of mutated HSCs over the years and computed their fitness. After escaping stochastic extinction, the population of mutated HSCs grew exponentially by 63±15% and 44±13% every year in the two patients respectively. To contrast the differentiation trajectories of the JAK2 -mutant HSCs with those of healthy HSCs, we simultaneously measured the full transcriptome and somatic mutations in single HSPCs in the two ET patients in whom we had performed whole genome sequencing and in one additional ET patient (N=3 total) and also in patients with polycythemia vera (PV) (N=3). We observed, at the time of MPN diagnosis, a consistent lineage bias of JAK2 -mutant HSPCs toward megakaryocyte-erythrocyte fate, across ET and PV patients. Exploiting our ability to discriminate JAK2 -mutant cells from JAK2 wild-type cells within individual MPN patients, we identified genes involved in antigen presentation and inflammation as differentially up-regulated in JAK2 -mutant HS

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Single-cell RNA-sequencing and subcellular spatial transcriptomics facilitate the translation of liver microphysiological systems for regulatory application

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Journal of Pharmaceutical Analysis 2023年第7期13卷 691-693页

作者： Dan Li Zhou Fang Qiang Shi Nicholas Zhang Binsheng Gong Weida Tong Ahmet F.Coskun Joshua Xu Division of Bioinformatics and Biostatistics National Center for Toxicological ResearchU.S.Food and Drug AdministrationJeffersonAR72079USA Wallace H.Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory UniversityAtlantaGA30332USA Machine Learning Graduate Program Georgia Institute of TechnologyAtlantaGA30332USA Division of Systems Biology National Center for Toxicological ResearchU.S.Food and Drug AdministrationJeffersonAR72079USA Interdisciplinary Bioengineering Graduate Program Georgia Institute of TechnologyAtlantaGA30332USA Parker H.Petit Institute for Bioengineering and Bioscience Georgia Institute of TechnologyAtlantaGA30332USA

Reducing the use of animal models in drug development and safety assessment has long been supported by the *** and Drug Administration(FDA).The report by Royal Society for the Prevention of Cruelty to Animals indicates that in 2020,experiments involved the use of over 100 million animals,with the United States leading the list by utilizing 20 million *** ethical considerations associated with animal testing and the costs in terms of time and money,animal models are not always effective in predicting human reactions to drug *** animal testing has been the traditional method for assessing the safety and efficacy of drugs.

关键词： money utilizing testing

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Context-dependent gene regulatory network reveals regulation dynamics and cell trajectories using unspliced transcripts

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Briefings in bioinformatics 2023年第2期24卷 bbac633页

作者： Tu, Yueh-Hua Juan, Hsueh-Fen Huang, Hsuan-Cheng The Bioinformatics Program Taiwan International Graduate Program Academia Sinica Taiwan Department of Life Science Center for Computational and Systems Biology National Taiwan University Taiwan Institute of Biomedical Informatics National Yang Ming Chiao Tung University Taiwan

Gene regulatory networks govern complex gene expression programs in various biological phenomena, including embryonic development, cell fate decisions and oncogenesis. Single-cell techniques are increasingly being used to study gene expression, providing higher resolution than traditional approaches. However, inferring a comprehensive gene regulatory network across different cell types remains a challenge. Here, we propose to construct context-dependent gene regulatory networks (CDGRNs) from single-cell RNA sequencing data utilizing both spliced and unspliced transcript expression levels. A gene regulatory network is decomposed into subnetworks corresponding to different transcriptomic contexts. Each subnetwork comprises the consensus active regulation pairs of transcription factors and their target genes shared by a group of cells, inferred by a Gaussian mixture model. We find that the union of gene regulation pairs in all contexts is sufficient to reconstruct differentiation trajectories. Functions specific to the cell cycle, cell differentiation or tissue-specific functions are enriched throughout the developmental process in each context. Surprisingly, we also observe that the network entropy of CDGRNs decreases along differentiation trajectories, indicating directionality in differentiation. Overall, CDGRN allows us to establish the connection between gene regulation at the molecular level and cell differentiation at the macroscopic level. © The Author(s) 2023.

关键词： Gaussian mixture model gene regulatory network single-cell RNA sequencing trajectory analysis

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Origin of Overstretching Transitions in Single-Stranded Nucleic Acids

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Physical Review Letters 2013年第18期111卷 188302-188302页

作者： Zackary N. Scholl Mahir Rabbi David Lee Laura Manson Hanna S-Gracz Piotr E. Marszalek Program in Computational Biology and Bioinformatics Duke University Durham North Carolina 27708 USA Department of Mechanical Engineering and Materials Science Center for Biologically Inspired Materials and Material Systems Duke University Durham North Carolina 27708 USA Department of Molecular and Structural Biochemistry North Carolina State University Raleigh North Carolina 27708 USA

We combined single-molecule force spectroscopy with nuclear magnetic resonance measurements and molecular mechanics simulations to examine overstretching transitions in single-stranded nucleic acids. In single-stranded DNA and single-stranded RNA there is a low-force transition that involves unwinding of the helical structure, along with base unstacking. We determined that the high-force transition that occurs in polydeoxyadenylic acid single-stranded DNA is caused by the cooperative forced flipping of the dihedral angle formed between four atoms, O5’-C5’-C4’-C3’ (γ torsion), in the nucleic acid backbone within the canonical B-type helix. The γ torsion also flips under force in A-type helices, where the helix is shorter and wider as compared to the B-type helix, but this transition is less cooperative than in the B type and does not generate a high-force plateau in the force spectrums of A-type helices. We find that a similar high-force transition can be induced in polyadenylic acid single-stranded RNA by urea, presumably due to disrupting the intramolecular hydrogen bonding in the backbone. We hypothesize that a pronounced high-force transition observed for B-type helices of double stranded DNA also involves a cooperative flip of the γ torsion. These observations suggest new fundamental relationships between the canonical structures of single-and double-stranded DNA and the mechanism of their molecular elasticity.

关键词： DNA

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