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The 5th International Symposium on Insect Physiology, Biochemistry and Molecular Biology

作者： Alexander S.Raikhel Tusar Saha Sourav Roy Lisa Johnson Keira Lucas Shiping Liu Bo Zhao Vlastimil Smykal Xiufeng Zhang Sang Woon Shin Jisu Ha Wei Dou Vladimir Kokoza Zhen Zou Department of Entomology and Institute for Integrative Genome Biology University of California Riverside Graduate Program in Cell Molecular and Developmental BiologyUniversity of California Riverside Graduate Program in Genomics Genetics and BioinformaticsUniversity of California Riverside The State Key Laboratory of Silkworm Genome Biology Southwest University College of Plant Protection Southwest University State Key Laboratory of Integrated Management of Pest Insects and Rodents Institute of ZoologyChinese Academy of Sciences

Mosquitoes transmit numerous devastating diseases to humans and animals due to obligatory blood feeding that is required for egg development. Elucidating molecular mechanisms underlying mosquito reproduction is of paramount importance for devising novel control approaches. In addition, mosquitoes represent outstanding models for investigating these events in insects in general. Two major insect hormones-juvenile hormone(JH) and20-hydroxyecdysone(20E)-regulate a plethora of physiological processes. In female mosquitoes,these hormones are responsible for controlling sequential reproductive phases. Transcriptomic analyses combined with RNA interference depletions of JH receptor Methoprene-tolerant(Met)and Ecdysone receptor(EcR) have revealed functions of these hormone receptors in activation and repression of gene cohorts during previtellogenic and vitellogenic phases, respectively. We identified how JH receptor mediates JH action on gene expression in mosquitoes and devised an approach of studying the subunit composition of this receptor. Using this technique we screened numerous natural compounds and isolated several molecules that serve as strong disruptors of JH receptor and JH action, providing a basis for developing a novel class of insecticides. We extensively investigated the role of Ecdysone Receptor in regulation of gene expression,uncovering the complexity of the 20 E genetic hierarchy that controls vitellogenic phase of female mosquito reproduction. Understanding of the molecular mechanisms of Ecdysone receptor-dependent gene repression is of great importance for devising future control methodologies. Small non-coding RNAs belonging to the class of micro RNAs(miR NA) have been implicated in regulation of numerous cellular and physiological processes in animals and plants. However, relatively little is known about mi RNA roles in non-Drosophilid insects. We have developed systemic and transgenic approaches for analyzing functions of miR NAs in mosquito repro

关键词： juvenile hormone methoprene-tolerant 20-hydroxyecdysone ecdysone receptor vitellogenesis microRNA

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Functional annotation of chemical libraries across diverse biological processes (vol 13, pg 982, 2017)

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NATURE CHEMICAL BIOLOGY 2017年第12期13卷 1286-1286页

作者： Piotrowski, Jeff S. Li, Sheena C. Deshpande, Raamesh Simpkins, Scott W. Nelson, Justin Yashiroda, Yoko Barber, Jacqueline M. Safizadeh, Hamid Wilson, Erin Okada, Hiroki Gebre, Abraham A. Kubo, Karen Torres, Nikko P. LeBlanc, Marissa A. Andrusiak, Kerry Okamoto, Reika Yoshimura, Mami DeRango-Adem, Eva van Leeuwen, Jolanda Shirahige, Katsuhiko Baryshnikova, Anastasia Brown, Grant W. Hirano, Hiroyuki Costanzo, Michael Andrews, Brenda Ohya, Yoshikazu Osada, Hiroyuki Yoshida, Minoru Myers, Chad L. Boone, Charles RIKEN Center for Sustainable Resource Science Wako Saitama Japan. Department of Computer Science and Engineering University of Minnesota-Twin Cities Minneapolis Minnesota USA. Bioinformatics and Computational Biology Program University of Minnesota-Twin Cities Minneapolis Minnesota USA. Department of Electrical and Computer Engineering University of Minnesota-Twin Cities Minneapolis Minnesota USA. Department of Integrated Biosciences Graduate School of Frontier Sciences University of Tokyo Kashiwa Chiba Japan. Donnelly Centre University of Toronto Toronto Ontario Canada. Institute of Molecular and Cellular Biosciences Center for Epigenetic Disease University of Tokyo Bunkyo-ku Tokyo Japan. Lewis-Sigler Institute for Integrative Genomics Princeton University Princeton New Jersey USA. Department of Biochemistry University of Toronto Toronto Ontario Canada.

Chemical-genetic approaches offer the potential for unbiased functional annotation of chemical libraries. Mutations can alter the response of cells in the presence of a compound, revealing chemical-genetic interactions that can elucidate a compound's mode of action. We developed a highly parallel, unbiased yeast chemical-genetic screening system involving three key components. First, in a drug-sensitive genetic background, we constructed an optimized diagnostic mutant collection that is predictive for all major yeast biological processes. Second, we implemented a multiplexed (768-plex) barcode-sequencing protocol, enabling the assembly of thousands of chemical-genetic profiles. Finally, based on comparison of the chemical-genetic profiles with a compendium of genome-wide genetic interaction profiles, we predicted compound functionality. Applying this high-throughput approach, we screened seven different compound libraries and annotated their functional diversity. We further validated biological process predictions, prioritized a diverse set of compounds, and identified compounds that appear to have dual modes of action.

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The Alternative Splicing Mutation Database: A hub for investigations of alternative splicing using mutational evidence

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BMC Research Notes 2008年第1期1卷 1-7页

作者： Bechtel, Jason M. Rajesh, Preeti Ilikchyan, Irina Deng, Ying Mishra, Pankaj K. Wang, Qi Wu, Xiaochun Afonin, Kirill A. Grose, William E. Wang, Ye Khuder, Sadik Fedorov, Alexei Program in Bioinformatics and Proteomics/Genomics University of Toledo Health Science Campus Toledo OH 43614 United States Dept. of Medical Microbiology and Immunology University of Toledo Health Science Campus Toledo OH 43614 United States Dept. of Basic Pharmaceutical Sciences South Carolina College of Pharmacy University of South Carolina Columbia SC 29208 United States Department of Biological Sciences Bowling Green State University Bowling Green OH 43403 United States College of Engineering University of Toledo Toledo OH 43606 United States Dept. of Medicine University of Toledo Health Science Campus Toledo OH 43614 United States

Background. Some mutations in the internal regions of exons occur within splicing enhancers and silencers, influencing the pattern of alternative splicing in the corresponding genes. To understand how these sequence changes affect splicing, we created a database of these mutations. Findings. The Alternative Splicing Mutation Database (ASMD) serves as a repository for all exonic mutations not associated with splicing junctions that measurably change the pattern of alternative splicing. In this initial published release (version 1.2), only human sequences are present, but the ASMD will grow to include other organisms, (see Availability and requirements section for the ASMD web address). This relational database allows users to investigate connections between mutations and features of the surrounding sequences, including flanking sequences, RNA secondary structures and strengths of splice junctions. Splicing effects of the mutations are quantified by the relative presence of alternative mRNA isoforms with and without a given mutation. This measure is further categorized by the accuracy of the experimental methods employed. The database currently contains 170 mutations in 66 exons, yet these numbers increase regularly. We developed an algorithm to derive a table of oligonucleotide Splicing Potential (SP) values from the ASMD dataset. We present the SP concept and tools in detail in our corresponding article. Conclusion. The current data set demonstrates that mutations affecting splicing are located throughout exons and might be enriched within local RNA secondary structures. Exons from the ASMD have below average splicing junction strength scores, but the difference is small and is judged not to be significant. © 2008 Bechtel et al;licensee BioMed Central Ltd.

关键词： Alternative Splice Splice Effect Splice Junction Alternative Splice Effect mRNA Isoforms

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EQTL AND MUTATIONAL ANALYSIS OF NB-LRR MEDIATED IMMUNITY TO POWDERY MILDEW

EQTL AND MUTATIONAL ANALYSIS OF NB-LRR MEDIATED IMMUNITY TO ...

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The 13th International Cereal Rusts and Powdery Mildews Conference(第13届国际禾谷类锈病与白粉病大会)

作者： Roger WISE Priyanka SURANA Greg FUERST Ruo XU Divya MISTRY Julie DICKERSON Dan NETTLETON Department of Statistics Iowa State UniversityAmesIowa 50011 Department of Plant Pathology and Microbiology Center for Plant Responses to Environmental StressesIowa State UniversityAmesIowa 50011 Department of StatisticsIowa State UniversityAmesIowa 50011 Bioinformatics and Computational Biology Graduate ProgramIowa State UniversityAmesIowa 50011 Department of Electrical and Computer Engineering Iowa State UniversityAmesIowa 50011USA Bioinformatics and Computational Biology Graduate ProgramIowa State UniversityAmesIowa 50011 Bioinformatics and Computational Biology Graduate Program Iowa State UniversityAmesIowa 50011 Department of Plant Pathology and MicrobiologyCenter for Plant Responses to Environmental StressesIowa State UniversityAmesIowa 50011 Department of Plant Pathology and Microbiology Center for Plant Responses to Environmental StressesIowa State UniversityAmesIowa 50011 Bioinformatics and Computational Biology Graduate Program Iowa State UniversityAmesIowa 50011 Crop and Insect GeneticsGenomicsand Informatics Research UnitU.S.Department of Agriculture-Agricultural Research ServiceIowa State UniversityAmesIowa 50011 Crop and Insect Genetics Genomicsand Informatics Research UnitU.S.Department of Agriculture-Agricultural Research ServiceIowa State UniversityAmesIowa 50011

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Evolution at the edge of expanding populations

arXiv

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arXiv 2017年

作者： Deforet, Maxime Carmona-Fontaine, Carlos Korolev, Kirill S. Xavier, Joao B. Sorbonne Université Centre National de la Recherche Rcientifique Laboratoire Jean Perrin LJP Paris75005 France Center for Genomics and Systems Biology Department of Biology New York University New York CityNY10003 United States Department of Physics Graduate Program in Bioinformatics Boston University BostonMA02215 Program in Computational Biology Memorial Sloan-Kettering Cancer Center New York CityNY10065 United States

Predicting evolution of expanding populations is critical to control biological threats such as invasive species and cancer metastasis. Expansion is primarily driven by reproduction and dispersal, but nature abounds with examples of evolution where organisms pay a reproductive cost to disperse faster. When does selection favor this 'survival of the fastest?' We searched for a simple rule, motivated by evolution experiments where swarming bacteria evolved into an hyperswarmer mutant which disperses ∼ 100% faster but pays a growth cost of ∼ 10% to make many copies of its flagellum. We analyzed a two-species model based on the Fisher equation to explain this observation: the population expansion rate (v) results from an interplay of growth (r) and dispersal (D) and is independent of the carrying capacity: v = 2 √rD. A mutant can take over the edge only if its expansion rate (v2) exceeds the expansion rate of the established species' (v1);this simple condition (v2> v1) determines the maximum cost in slower growth that a faster mutant can pay and still be able to take over. Numerical simulations and time-course experiments where we tracked evolution by imaging bacteria suggest that our findings are general: less favorable conditions delay but do not entirely prevent the success of the fastest. Thus, the expansion rate defines a traveling wave fitness, which could be combined with trade-offs to predict evolution of expanding populations. Copyright © 2017, The Authors. All rights reserved.

关键词： Bacteria

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Graph Representation Learning in Biomedicine

arXiv

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arXiv 2021年

作者： Li, Michelle M. Huang, Kexin Zitnik, Marinka Bioinformatics and Integrative Genomics Program Harvard Medical School BostonMA02115 United States Health Data Science Program Harvard T.H. Chan School of Public Health BostonMA02115 United States Department of Biomedical Informatics Harvard Medical School BostonMA02115 United States Broad Institute of MIT and Harvard CambridgeMA02142 United States Harvard Data Science Initiative CambridgeMA02138 United States

Biomedical networks (or graphs) are universal descriptors for systems of interacting elements, from molecular interactions and disease co-morbidity to healthcare systems and scientific knowledge. Advances in artificial intelligence, specifically deep learning, have enabled us to model, analyze, and learn with such networked data. In this review, we put forward an observation that long-standing principles of systems biology and medicine-while often unspoken in machine learning research-provide the conceptual grounding for representation learning on graphs, explain its current successes and limitations, and even inform future advancements. We synthesize a spectrum of algorithmic approaches that, at their core, leverage graph topology to embed networks into compact vector spaces. We also capture the breadth of ways in which representation learning has dramatically improved the state-of-the-art in biomedical machine learning. Exemplary domains covered include identifying variants underlying complex traits, disentangling behaviors of single cells and their effects on health, assisting in diagnosis and treatment of patients, and developing safe and effective medicines. © 2021, CC BY.

关键词： Vector spaces

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Remarkable sequence signatures in archaeal genomes

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Archaea 2003年第3期1卷 185-190页

作者： Fadiel, Ahmed Lithwick, Stuart Ganji, Gopi Scherer, Stephen W. Center for Applied Genomics Hospital for Sick Children Toronto Ont. M5G 1Z8 Canada Bioinformatics Supercomputing Centre Genom. and Genetics Biology Program Hospital for Sick Children Toronto Ont. M5G 1Z8 Canada

Complete archaeal genomes were probed for the presence of long (≥ 25 bp) oligonucleotide repeats (words). We detected the presence of many words distributed in tandem with narrow ranges of periodicity (i.e., spacer length between repeats). Similar words were not identified in genomes of non-archaeal species, namely Escherichia coli, Bacillus subtilis, Haemophilus influenzae, Mycoplasma genitalium and Mycoplasma pneumoniae. BLAST similarity searches against the GenBank nucleotide sequence database revealed that these words were archaeal species-specific, indicating that they are of a signature character. Sequence analysis and genome viewing tools showed these repeats to be restricted to non-coding regions. Thus, archaea appear to possess a non-coding genomic signature that is absent in bacterial species. The identification of a species-specific genomic signature would be of great value to archaeal genome mapping, evolutionary studies and analyses of genome complexity.

关键词： Archaea bioinformatics Comparative genomics Genome signature Oligonucleotide frequencies

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SYSTEMS BIOLOGY IN BARLEY POWDERY MILDEW INTERACTIONS

SYSTEMS BIOLOGY IN BARLEY POWDERY MILDEW INTERACTIONS

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The 13th International Cereal Rusts and Powdery Mildews Conference(第13届国际禾谷类锈病与白粉病大会)

作者： Roger WISE Priyanka SURANA Greg FUERST Ruo XU Dan NETTLETON Divya MISTRY Julie DICKERSON Lin WANG Tom BRUTNELL Department of Plant Pathology and Microbiology Center for Plant Responses to Environmental StressesIowa State UniversityAmesIowa 50011USA Department of Statistics Iowa State UniversityAmesIowa 50011USA Bioinformatics and Computational Biology Graduate ProgramIowa State UniversityAmesIowa 50011USA Bioinformatics and Computational Biology Graduate ProgramIowa State UniversityAmesIowa 50011USA Bioinformatics and Computational Biology Graduate Program Iowa State UniversityAmesIowa 50011USA Department of Plant Pathology and MicrobiologyCenter for Plant Responses to Environmental StressesIowa State UniversityAmesIowa 50011USA Crop and Insect Genetics Genomicsand Informatics Research UnitU.S.Department of Agriculture-Agricultural Research ServiceIowa State UniversityAmesIowa 50011USA Department of Plant Pathology and Microbiology Center for Plant Responses to Environmental StressesIowa State UniversityAmesIowa 50011USA Department of StatisticsIowa State UniversityAmesIowa 50011USA Bioinformatics and Computational Biology Graduate ProgramIowa State UniversityAmesIowa 50011USA Bioinformatics and Computational Biology Graduate Program Iowa State UniversityAmesIowa 50011USA Crop and Insect GeneticsGenomicsand Informatics Research UnitU.S.Department of Agriculture-Agricultural Research ServiceIowa State UniversityAmesIowa 50011USA Department of Electrical and Computer Engineering Iowa State UniversityAmesIowa 50011USA Boyce Thompson Institute for Plant ResearchCornell UniversityIthacaNY

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Single-nucleus analysis of accessible chromatin in developing mouse forebrain reveals cell-type-specific transcriptional regulation (vol 21, pg 432, 2018)

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NATURE NEUROSCIENCE 2018年第7期21卷 1015-1015页

作者： Preissl, Sebastian Fang, Rongxin Huang, Hui Zhao, Yuan Raviram, Ramya Gorkin, David U. Zhang, Yanxiao Sos, Brandon C. Afzal, Veena Dickel, Diane E. Kuan, Samantha Visel, Axel Pennacchio, Len A. Zhang, Kun Ren, Bing Ludwig Institute for Cancer Research La Jolla CA USA. Center for Epigenomics Department of Cellular and Molecular Medicine University of California San Diego School of Medicine La Jolla CA USA. Bioinformatics and Systems Biology Graduate Program University of California San Diego La Jolla CA USA. Biomedical Sciences Graduate Program University of California San Diego La Jolla CA USA. Department of Bioengineering University of California San Diego La Jolla CA USA. Environmental Genomics and Systems Biology Division Lawrence Berkeley National Laboratory Berkeley CA USA. US Department of Energy Joint Genome Institute Walnut Creek CA USA. School of Natural Sciences University of California Merced Merced CA USA. Comparative Biochemistry Program University of California Berkeley Berkeley CA USA. Ludwig Institute for Cancer Research La Jolla CA USA. biren@ucsd.edu. Center for Epigenomics Department of Cellular and Molecular Medicine University of California San Diego School of Medicine La Jolla CA USA. biren@ucsd.edu. Institute of Genomic Medicine Moores Cancer Center University of California San Diego School of Medicine La Jolla CA USA. biren@ucsd.edu.

Analysis of chromatin accessibility can reveal transcriptional regulatory sequences, but heterogeneity of primary tissues poses a significant challenge in mapping the precise chromatin landscape in specific cell types. Here we report single-nucleus ATAC-seq, a combinatorial barcoding-assisted single-cell assay for transposase-accessible chromatin that is optimized for use on flash-frozen primary tissue samples. We apply this technique to the mouse forebrain through eight developmental stages. Through analysis of more than 15,000 nuclei, we identify 20 distinct cell populations corresponding to major neuronal and non-neuronal cell types. We further define cell-type-specific transcriptional regulatory sequences, infer potential master transcriptional regulators and delineate developmental changes in forebrain cellular composition. Our results provide insight into the molecular and cellular dynamics that underlie forebrain development in the mouse and establish technical and analytical frameworks that are broadly applicable to other heterogeneous tissues.

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Targeting protein-protein interaction interfaces with antiviral N protein inhibitor in SARS-CoV-2

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Biophysical Journal 2024年第4期123卷 478-488页

作者： Hong, Jhen-Yi Lin, Shih-Chao Kehn-Hall, Kylene Zhang, Kai-Min Luo, Shun-Yuan Wu, Hung-Yi Chang, Sui-Yuan Hou, Ming-Hon Institute of Genomics and Bioinformatics and Department of Life Sciences National Chung Hsing University Taichung Taiwan Bachelor Degree Program in Marine Biotechnology College of Life Sciences National Taiwan Ocean University Keelung Taiwan Department of Biomedical Sciences and Pathobiology Virginia-Maryland College of Veterinary Medicine Virginia Polytechnic Institute and State University Blacksburg VA United States Center for Emerging Zoonotic and Arthropod-borne Pathogens Virginia Polytechnic Institute and State University Blacksburg VA United States Department of Chemistry National Chung Hsing University Taichung Taiwan Graduate Institute of Veterinary Pathobiology College of Veterinary Medicine National Chung Hsing University. Taichung Taiwan Department of Clinical Laboratory Sciences and Medical Biotechnology College of Medicine National Taiwan University Taipei Taiwan PhD Program in Medical Biotechnology National Chung Hsing University Taichung Taiwan Biotechnology Center National Chung Hsing University Taichung Taiwan

Coronaviruses not only pose significant global public health threats but also cause extensive damage to livestock-based industries. Previous studies have shown that 5-benzyloxygramine (P3) targets the Middle East respiratory syndrome coronavirus (MERS-CoV) nucleocapsid (N) protein N-terminal domain (N-NTD), inducing non-native protein-protein interactions (PPIs) that impair N protein function. Moreover, P3 exhibits broad-spectrum antiviral activity against CoVs. The sequence similarity of N proteins is relatively low among CoVs, further exhibiting notable variations in the hydrophobic residue responsible for non-native PPIs in the N-NTD. Therefore, to ascertain the mechanism by which P3 demonstrates broad-spectrum anti-CoV activity, we determined the crystal structure of the SARS-CoV-2 N-NTD:P3 complex. We found that P3 was positioned in the dimeric N-NTD via hydrophobic contacts. Compared with the interfaces in MERS-CoV N-NTD, P3 had a reversed orientation in SARS-CoV-2 N-NTD. The Phe residue in the MERS-CoV N-NTD:P3 complex stabilized both P3 moieties. However, in the SARS-CoV-2 N-NTD:P3 complex, the Ile residue formed only one interaction with the P3 benzene ring. Moreover, the pocket in the SARS-CoV-2 N-NTD:P3 complex was more hydrophobic, favoring the insertion of the P3 benzene ring into the complex. Nevertheless, hydrophobic interactions remained the primary stabilizing force in both complexes. These findings suggested that despite the differences in the sequence, P3 can accommodate a hydrophobic pocket in N-NTD to mediate a non-native PPI, enabling its effectiveness against various CoVs. © 2024 Biophysical Society

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