1,581 results on '"Sternberg, Paul W."'
Search Results
2. AI-aided Geometric Design of Anti-infection Catheters
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Zhou, Tingtao, Wan, Xuan, Huang, Daniel Zhengyu, Li, Zongyi, Peng, Zhiwei, Anandkumar, Anima, Brady, John F., Sternberg, Paul W., and Daraio, Chiara
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Physics - Medical Physics ,Condensed Matter - Soft Condensed Matter ,Physics - Biological Physics ,Physics - Fluid Dynamics - Abstract
Bacteria can swim upstream due to hydrodynamic interactions with the fluid flow in a narrow tube, and pose a clinical threat of urinary tract infection to patients implanted with catheters. Coatings and structured surfaces have been proposed as a way to suppress bacterial contamination in catheters. However, there is no surface structuring or coating approach to date that thoroughly addresses the contamination problem. Here, based on the physical mechanism of upstream swimming, we propose a novel geometric design, optimized by an AI model predicting in-flow bacterial dynamics. The AI method, based on Fourier neural operator, offers significant speedups over traditional simulation methods. Using Escherichia coli, we demonstrate the anti-infection mechanism in quasi-2D micro-fluidic experiments and evaluate the effectiveness of the design in 3Dprinted prototype catheters under clinical flow rates. Our catheter design shows 1-2 orders of magnitude improved suppression of bacterial contamination at the upstream end of the catheter, potentially prolonging the in-dwelling time for catheter use and reducing the overall risk of catheter-associated urinary tract infections., Comment: maint text 4 figures, SI 5 figures
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- 2023
3. Single-nucleus resolution mapping of the adult C. elegans and its application to elucidate inter- and trans-generational response to alcohol
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Truong, Lisa, Chen, Yen-Wei, Barrere-Cain, Rio, Levenson, Max T, Shuck, Karissa, Xiao, Wen, da Veiga Beltrame, Eduardo, Panter, Blake, Reich, Ella, Sternberg, Paul W, Yang, Xia, and Allard, Patrick
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Biological Sciences ,Genetics ,Substance Misuse ,Human Genome ,Alcoholism ,Alcohol Use and Health ,1.1 Normal biological development and functioning ,2.1 Biological and endogenous factors ,Generic health relevance ,Good Health and Well Being ,Animals ,Adult ,Humans ,Caenorhabditis elegans ,Transcriptome ,Gene Expression Profiling ,Ethanol ,RNA ,Small Nuclear ,C. elegans ,CP: Molecular biology ,alcohol ,ethanol ,germline ,snRNA-seq ,Biochemistry and Cell Biology ,Medical Physiology ,Biological sciences - Abstract
Single-cell transcriptomic platforms provide an opportunity to map an organism's response to environmental cues with high resolution. Here, we applied single-nucleus RNA sequencing (snRNA-seq) to establish the tissue and cell type-resolved transcriptome of the adult C. elegans and characterize the inter- and trans-generational transcriptional impact of ethanol. We profiled the transcriptome of 41,749 nuclei resolving into 31 clusters, representing a diverse array of adult cell types including syncytial tissues. Following exposure to human-relevant doses of alcohol, several germline, striated muscle, and neuronal clusters were identified as being the most transcriptionally impacted at the F1 and F3 generations. The effect on germline clusters was confirmed by phenotypic enrichment analysis as well as by functional validation, which revealed a remarkable inter- and trans-generational increase in germline apoptosis, aneuploidy, and embryonic lethality. Together, snRNA-seq represents a valuable approach for the detailed examination of an adult organism's response to environmental exposures.
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- 2023
4. The Gene Ontology knowledgebase in 2023
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Aleksander, Suzi A, Balhoff, James, Carbon, Seth, Cherry, J Michael, Drabkin, Harold J, Ebert, Dustin, Feuermann, Marc, Gaudet, Pascale, Harris, Nomi L, Hill, David P, Lee, Raymond, Mi, Huaiyu, Moxon, Sierra, Mungall, Christopher J, Muruganugan, Anushya, Mushayahama, Tremayne, Sternberg, Paul W, Thomas, Paul D, Van Auken, Kimberly, Ramsey, Jolene, Siegele, Deborah A, Chisholm, Rex L, Fey, Petra, Aspromonte, Maria Cristina, Nugnes, Maria Victoria, Quaglia, Federica, Tosatto, Silvio, Giglio, Michelle, Nadendla, Suvarna, Antonazzo, Giulia, Attrill, Helen, dos Santos, Gil, Marygold, Steven, Strelets, Victor, Tabone, Christopher J, Thurmond, Jim, Zhou, Pinglei, Ahmed, Saadullah H, Asanitthong, Praoparn, Buitrago, Diana Luna, Erdol, Meltem N, Gage, Matthew C, Kadhum, Mohamed Ali, Li, Kan Yan Chloe, Long, Miao, Michalak, Aleksandra, Pesala, Angeline, Pritazahra, Armalya, Saverimuttu, Shirin CC, Su, Renzhi, Thurlow, Kate E, Lovering, Ruth C, Logie, Colin, Oliferenko, Snezhana, Blake, Judith, Christie, Karen, Corbani, Lori, Dolan, Mary E, Ni, Li, Sitnikov, Dmitry, Smith, Cynthia, Cuzick, Alayne, Seager, James, Cooper, Laurel, Elser, Justin, Jaiswal, Pankaj, Gupta, Parul, Naithani, Sushma, Lera-Ramirez, Manuel, Rutherford, Kim, Wood, Valerie, De Pons, Jeffrey L, Dwinell, Melinda R, Hayman, G Thomas, Kaldunski, Mary L, Kwitek, Anne E, Laulederkind, Stanley JF, Tutaj, Marek A, Vedi, Mahima, Wang, Shur-Jen, D’Eustachio, Peter, Aimo, Lucila, Axelsen, Kristian, Bridge, Alan, Hyka-Nouspikel, Nevila, Morgat, Anne, Engel, Stacia R, Karra, Kalpana, Miyasato, Stuart R, Nash, Robert S, Skrzypek, Marek S, Weng, Shuai, Wong, Edith D, Bakker, Erika, and Berardini, Tanya Z
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Biological Sciences ,Bioinformatics and Computational Biology ,Genetics ,1.1 Normal biological development and functioning ,Underpinning research ,Gene Ontology ,Proteins ,Molecular Sequence Annotation ,Databases ,Genetic ,Computational Biology ,gene annotation ,gene function ,knowledgebase ,knowledge graphs ,Gene Ontology Consortium ,Developmental Biology ,Biochemistry and cell biology - Abstract
The Gene Ontology (GO) knowledgebase (http://geneontology.org) is a comprehensive resource concerning the functions of genes and gene products (proteins and noncoding RNAs). GO annotations cover genes from organisms across the tree of life as well as viruses, though most gene function knowledge currently derives from experiments carried out in a relatively small number of model organisms. Here, we provide an updated overview of the GO knowledgebase, as well as the efforts of the broad, international consortium of scientists that develops, maintains, and updates the GO knowledgebase. The GO knowledgebase consists of three components: (1) the GO-a computational knowledge structure describing the functional characteristics of genes; (2) GO annotations-evidence-supported statements asserting that a specific gene product has a particular functional characteristic; and (3) GO Causal Activity Models (GO-CAMs)-mechanistic models of molecular "pathways" (GO biological processes) created by linking multiple GO annotations using defined relations. Each of these components is continually expanded, revised, and updated in response to newly published discoveries and receives extensive QA checks, reviews, and user feedback. For each of these components, we provide a description of the current contents, recent developments to keep the knowledgebase up to date with new discoveries, and guidance on how users can best make use of the data that we provide. We conclude with future directions for the project.
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- 2023
5. Differential processing of a chemosensory cue across life stages sharing the same valence state in Caenorhabditis elegans.
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Banerjee, Navonil, Shih, Pei-Yin, Rojas Palato, Elisa J, Sternberg, Paul W, and Hallem, Elissa A
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Interneurons ,Animals ,Caenorhabditis elegans ,Carbon Dioxide ,Caenorhabditis elegans Proteins ,Cues ,Signal Transduction ,Larva ,behavior ,carbon dioxide ,chemotaxis ,dauer larva ,neural circuits ,Neurosciences ,Behavioral and Social Science ,Basic Behavioral and Social Science ,1.1 Normal biological development and functioning ,Underpinning research ,Neurological - Abstract
Many chemosensory cues evoke responses of the same valence under widely varying physiological conditions. It remains unclear whether similar or distinct neural mechanisms are involved in the detection and processing of such chemosensory cues across contexts. We show that in Caenorhabditis elegans, a chemosensory cue is processed by distinct neural mechanisms at two different life stages that share the same valence state. Both starved adults and dauer larvae are attracted to carbon dioxide (CO2), but CO2 evokes different patterns of neural activity and different motor outputs at the two life stages. Moreover, the same interneuron within the CO2 microcircuit plays a different role in driving CO2-evoked motor output at the two life stages. The dauer-specific patterns of CO2-evoked activity in this interneuron require a dauer-specific gap junction complex and insulin signaling. Our results demonstrate that functionally distinct microcircuits are engaged in response to a chemosensory cue that triggers the same valence state at different life stages, revealing an unexpected complexity to chemosensory processing.
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- 2023
6. Toward implementing autonomous adaptive data acquisition for scanning hyperspectral imaging of biological systems
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Holman, Elizabeth A, Krishnan, Harinarayan, Holman, Derek R, Holman, Hoi-Ying N, and Sternberg, Paul W
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Engineering ,Macromolecular and Materials Chemistry ,Materials Engineering ,Chemical Sciences ,Bioengineering ,Condensed Matter Physics ,Macromolecular and materials chemistry ,Materials engineering - Abstract
Autonomous experimentation is an emerging area of research, primarily related to autonomous vehicles, scientific combinatorial discovery approaches in materials science and drug discovery, and iterative research loops of planning, experimentation, and analysis. However, autonomous approaches developed in these contexts are difficult to apply to high-dimensional mapping technologies, such as scanning hyperspectral imaging of biological systems, due to sample complexity and heterogeneity. We briefly cover the history of adaptive sampling algorithms and surrogate modeling in order to define autonomous adaptive data acquisition as an objective-based, flexible building block for future biological imaging experimentation driven by intelligent infrastructure. We subsequently summarize the recent implementations of autonomous adaptive data acquisition (AADA) for scanning hyperspectral imaging, assess how these address the difficulties of autonomous approaches in hyperspectral imaging, and highlight the AADA design variation from a goal-oriented perspective. Finally, we present a modular AADA architecture that embeds AADA-driven flexible building blocks to address the challenge of time resolution for high-dimensional scanning hyperspectral imaging of nonequilibrium dynamical systems. In our example research-driven experimental design case, we propose an AADA infrastructure for time-resolved, noninvasive, and label-free scanning hyperspectral imaging of living biological systems. This AADA infrastructure can accurately target the correct state of the system for experimental workflows that utilize subsequent expensive, high-information-content analytical techniques.
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- 2023
7. The alliance of genome resources: transforming comparative genomics
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Bult, Carol J. and Sternberg, Paul W.
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- 2023
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8. Semantic representation of neural circuit knowledge in Caenorhabditis elegans
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Prakash, Sharan J., Van Auken, Kimberly M., Hill, David P., and Sternberg, Paul W.
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- 2023
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9. WormBase in 2022—data, processes, and tools for analyzing Caenorhabditis elegans
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Davis, Paul, Zarowiecki, Magdalena, Arnaboldi, Valerio, Becerra, Andrés, Cain, Scott, Chan, Juancarlos, Chen, Wen J, Cho, Jaehyoung, da Veiga Beltrame, Eduardo, Diamantakis, Stavros, Gao, Sibyl, Grigoriadis, Dionysis, Grove, Christian A, Harris, Todd W, Kishore, Ranjana, Le, Tuan, Lee, Raymond YN, Luypaert, Manuel, Müller, Hans-Michael, Nakamura, Cecilia, Nuin, Paulo, Paulini, Michael, Quinton-Tulloch, Mark, Raciti, Daniela, Rodgers, Faye H, Russell, Matthew, Schindelman, Gary, Singh, Archana, Stickland, Tim, Van Auken, Kimberly, Wang, Qinghua, Williams, Gary, Wright, Adam J, Yook, Karen, Berriman, Matt, Howe, Kevin L, Schedl, Tim, Stein, Lincoln, and Sternberg, Paul W
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Biological Sciences ,Genetics ,Human Genome ,Generic health relevance ,Animals ,Caenorhabditis ,Caenorhabditis elegans ,Databases ,Genetic ,Genome ,Genomics ,Humans ,Nematoda ,Caenorhabditis elegans ,annotation ,caenorhabditis ,community ,curation ,data ,database ,gene ,health ,human ,literature ,mining ,model ,nematode ,platform ,research ,resource ,software ,tools ,Developmental Biology ,Biochemistry and cell biology - Abstract
WormBase (www.wormbase.org) is the central repository for the genetics and genomics of the nematode Caenorhabditis elegans. We provide the research community with data and tools to facilitate the use of C. elegans and related nematodes as model organisms for studying human health, development, and many aspects of fundamental biology. Throughout our 22-year history, we have continued to evolve to reflect progress and innovation in the science and technologies involved in the study of C. elegans. We strive to incorporate new data types and richer data sets, and to provide integrated displays and services that avail the knowledge generated by the published nematode genetics literature. Here, we provide a broad overview of the current state of WormBase in terms of data type, curation workflows, analysis, and tools, including exciting new advances for analysis of single-cell data, text mining and visualization, and the new community collaboration forum. Concurrently, we continue the integration and harmonization of infrastructure, processes, and tools with the Alliance of Genome Resources, of which WormBase is a founding member.
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- 2022
10. Body stiffness is a mechanical property that facilitates contact-mediated mate recognition in Caenorhabditis elegans
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Weng, Jen-Wei, Park, Heenam, Valotteau, Claire, Chen, Rui-Tsung, Essmann, Clara L., Pujol, Nathalie, Sternberg, Paul W., and Chen, Chun-Hao
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- 2023
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11. Autonomous adaptive data acquisition for scanning hyperspectral imaging.
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Holman, Elizabeth A, Fang, Yuan-Sheng, Chen, Liang, DeWeese, Michael, Holman, Hoi-Ying N, and Sternberg, Paul W
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Animals ,Caenorhabditis elegans ,Gene Expression Regulation ,Models ,Biological ,Time Factors ,Image Processing ,Computer-Assisted ,Databases ,Factual ,Hyperspectral Imaging - Abstract
Non-invasive and label-free spectral microscopy (spectromicroscopy) techniques can provide quantitative biochemical information complementary to genomic sequencing, transcriptomic profiling, and proteomic analyses. However, spectromicroscopy techniques generate high-dimensional data; acquisition of a single spectral image can range from tens of minutes to hours, depending on the desired spatial resolution and the image size. This substantially limits the timescales of observable transient biological processes. To address this challenge and move spectromicroscopy towards efficient real-time spatiochemical imaging, we developed a grid-less autonomous adaptive sampling method. Our method substantially decreases image acquisition time while increasing sampling density in regions of steeper physico-chemical gradients. When implemented with scanning Fourier Transform infrared spectromicroscopy experiments, this grid-less adaptive sampling approach outperformed standard uniform grid sampling in a two-component chemical model system and in a complex biological sample, Caenorhabditis elegans. We quantitatively and qualitatively assess the efficiency of data acquisition using performance metrics and multivariate infrared spectral analysis, respectively.
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- 2020
12. Signaling by AWC Olfactory Neurons Is Necessary for Caenorhabditis elegans' Response to Prenol, an Odor Associated with Nematode-Infected Insects
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Baiocchi, Tiffany, Anesko, Kyle, Mercado, Nathan, Park, Heenam, Kin, Kassandra, Strickhouser-Monzon, Brandon, Robles, Priscila, Bowman, Christian, Wang, Han, Sternberg, Paul W, and Dillman, Adler R
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Biological Sciences ,Genetics ,Infectious Diseases ,Animals ,Caenorhabditis elegans ,Caenorhabditis elegans Proteins ,Chemoreceptor Cells ,Endoribonucleases ,Hemiterpenes ,Lectins ,C-Type ,Odorants ,Pentanols ,Smell ,prenol ,3-methyl-2-buten-1-ol ,dcap-1 ,dcap-2 ,clec-39 ,Developmental Biology ,Biochemistry and cell biology - Abstract
Chemosensation plays a role in the behaviors and life cycles of numerous organisms, including nematodes. Many guilds of nematodes exist, ranging from the free-living Caenorhabditis elegans to various parasitic species such as entomopathogenic nematodes (EPNs), which are parasites of insects. Despite ecological differences, previous research has shown that both EPNs and C. elegans respond to prenol (3-methyl-2-buten-1-ol), an odor associated with EPN infections. However, it is unclear how C. elegans responds to prenol. By utilizing natural variation and genetic neuron ablation to investigate the response of C. elegans to prenol, we found that the AWC neurons are involved in the detection of prenol and that several genes (including dcap-1, dcap-2, and clec-39) influence response to this odorant. Furthermore, we identified that the response to prenol is mediated by the canonically proposed pathway required for other AWC-sensed attractants. However, upon testing genetically diverse isolates, we found that the response of some strains to prenol differed from their response to isoamyl alcohol, suggesting that the pathways mediating response to these two odorants may be genetically distinct. Further, evaluations leveraging natural variation and genome wide association revealed specific genes that influence nematode behavior and provide a foundation for future studies to better understand the role of prenol in nematode behavioral ecology.
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- 2020
13. Single-tissue proteomics in Caenorhabditis elegans reveals proteins resident in intestinal lysosome-related organelles
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Tan, Chieh-Hsiang, primary, Wang, Ting-Yu, additional, Park, Heenam, additional, Lomenick, Brett, additional, Chou, Tsui-Fen, additional, and Sternberg, Paul W., additional
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- 2024
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14. CYK-1/Formin activation in cortical RhoA signaling centers promotes organismal left–right symmetry breaking
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Middelkoop, Teije C., Garcia-Baucells, Júlia, Quintero-Cadena, Porfirio, Pimpale, Lokesh G., Yazdi, Shahrzad, Sternberg, Paul W., Gross, Peter, and Grill, Stephan W.
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- 2021
15. Possible stochastic sex determination in Bursaphelenchus nematodes
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Shinya, Ryoji, Sun, Simo, Dayi, Mehmet, Tsai, Isheng Jason, Miyama, Atsushi, Chen, Anthony Fu, Hasegawa, Koichi, Antoshechkin, Igor, Kikuchi, Taisei, and Sternberg, Paul W.
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- 2022
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16. Extrasynaptic acetylcholine signaling through a muscarinic receptor regulates cell migration
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Kato, Mihoko, Kolotuev, Irina, Cunha, Alexandre, Gharib, Shahla, and Sternberg, Paul W.
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- 2021
17. Sensory integration of food availability and population density during the diapause exit decision involves insulin-like signaling inCaenorhabditis elegans
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Zhang, Mark G, primary, Seyedolmohadesin, Maedeh, additional, Hawk, Soraya, additional, Park, Heenam, additional, Finnen, Nerissa, additional, Schroeder, Frank, additional, Venkatachalam, Vivek, additional, and Sternberg, Paul W, additional
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- 2024
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18. Single-tissue proteomics in Caenorhabditis elegans reveals proteins resident in intestinal lysosome-related organelles.
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Chieh-Hsiang Tan, Ting-Yu Wang, Heenam Park, Lomenick, Brett, Tsui-Fen Chou, and Sternberg, Paul W.
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CAENORHABDITIS elegans ,PROTEOMICS ,ORGANELLES ,PROTEINS ,NUTRIENT uptake ,UTILITY theory - Abstract
The nematode intestine is the primary site for nutrient uptake and storage as well as the synthesis of biomolecules; lysosome-related organelles known as gut granules are important for many of these functions. Aspects of intestine biology are not well understood, including the export of the nutrients it imports and the molecules it synthesizes, as well as the complete functions and protein content of the gut granules. Here, we report a mass spectrometry (MS)-based proteomic analysis of the intestine of the Caenorhabditis elegans and of its gut granules. Overall, we identified approximately 5,000 proteins each in the intestine and the gonad and showed that most of these proteins can be detected in samples extracted from a single worm, suggesting the feasibility of individual-level genetic analysis using proteomes. Comparing proteomes and published transcriptomes of the intestine and the gonad, we identified proteins that appear to be synthesized in the intestine and then transferred to the gonad. To identify gut granule proteins, we compared the proteome of individual intestines deficient in gut granules to the wild type. The identified gut granule proteome includes proteins known to be exclusively localized to the granules and additional putative gut granule proteins. We selected two of these putative gut granule proteins for validation via immunohistochemistry, and our successful confirmation of both suggests that our strategy was effective in identifying the gut granule proteome. Our results demonstrate the practicability of single-tissue MS--based proteomic analysis in small organisms and in its future utility. [ABSTRACT FROM AUTHOR]
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- 2024
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19. WormBase 2024: status and transitioning to Alliance infrastructure.
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Sternberg, Paul W, Auken, Kimberly Van, Wang, Qinghua, Wright, Adam, Yook, Karen, Zarowiecki, Magdalena, Arnaboldi, Valerio, Becerra, Andrés, Brown, Stephanie, Cain, Scott, Chan, Juancarlos, Chen, Wen J, Cho, Jaehyoung, Davis, Paul, Diamantakis, Stavros, Dyer, Sarah, Grigoriadis, Dionysis, Grove, Christian A, Harris, Todd, and Howe, Kevin
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DATABASES , *GENOMICS , *INFORMATION resources , *BIOINFORMATICS , *CAENORHABDITIS elegans , *GENETICS - Abstract
WormBase has been the major repository and knowledgebase of information about the genome and genetics of Caenorhabditis elegans and other nematodes of experimental interest for over 2 decades. We have 3 goals: to keep current with the fast-paced C. elegans research, to provide better integration with other resources, and to be sustainable. Here, we discuss the current state of WormBase as well as progress and plans for moving core WormBase infrastructure to the Alliance of Genome Resources (the Alliance). As an Alliance member, WormBase will continue to interact with the C. elegans community, develop new features as needed, and curate key information from the literature and large-scale projects. [ABSTRACT FROM AUTHOR]
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- 2024
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20. Predicting gene essentiality in Caenorhabditis elegans by feature engineering and machine-learning
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Campos, Tulio L., Korhonen, Pasi K., Sternberg, Paul W., Gasser, Robin B., and Young, Neil D.
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- 2020
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21. AI-aided geometric design of anti-infection catheters
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Zhou, Tingtao, primary, Wan, Xuan, additional, Huang, Daniel Zhengyu, additional, Li, Zongyi, additional, Peng, Zhiwei, additional, Anandkumar, Anima, additional, Brady, John F., additional, Sternberg, Paul W., additional, and Daraio, Chiara, additional
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- 2024
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22. Muscle Logic: New Knowledge Resource for Anatomy Enables Comprehensive Searches of the Literature on the Feeding Muscles of Mammals
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Druzinsky, Robert E, Balhoff, James P, Crompton, Alfred W, Done, James, German, Rebecca Z, Haendel, Melissa A, Herrel, Anthony, Herring, Susan W, Lapp, Hilmar, Mabee, Paula M, Muller, Hans-Michael, Mungall, Christopher J, Sternberg, Paul W, Van Auken, Kimberly, Vinyard, Christopher J, Williams, Susan H, and Wall, Christine E
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Data Management and Data Science ,Information and Computing Sciences ,Biological Sciences ,Digestive Diseases ,Animals ,Databases as Topic ,Humans ,Oropharynx ,Pharyngeal Muscles ,Search Engine ,General Science & Technology - Abstract
BackgroundIn recent years large bibliographic databases have made much of the published literature of biology available for searches. However, the capabilities of the search engines integrated into these databases for text-based bibliographic searches are limited. To enable searches that deliver the results expected by comparative anatomists, an underlying logical structure known as an ontology is required.Development and testing of the ontologyHere we present the Mammalian Feeding Muscle Ontology (MFMO), a multi-species ontology focused on anatomical structures that participate in feeding and other oral/pharyngeal behaviors. A unique feature of the MFMO is that a simple, computable, definition of each muscle, which includes its attachments and innervation, is true across mammals. This construction mirrors the logical foundation of comparative anatomy and permits searches using language familiar to biologists. Further, it provides a template for muscles that will be useful in extending any anatomy ontology. The MFMO is developed to support the Feeding Experiments End-User Database Project (FEED, https://feedexp.org/), a publicly-available, online repository for physiological data collected from in vivo studies of feeding (e.g., mastication, biting, swallowing) in mammals. Currently the MFMO is integrated into FEED and also into two literature-specific implementations of Textpresso, a text-mining system that facilitates powerful searches of a corpus of scientific publications. We evaluate the MFMO by asking questions that test the ability of the ontology to return appropriate answers (competency questions). We compare the results of queries of the MFMO to results from similar searches in PubMed and Google Scholar.Results and significanceOur tests demonstrate that the MFMO is competent to answer queries formed in the common language of comparative anatomy, but PubMed and Google Scholar are not. Overall, our results show that by incorporating anatomical ontologies into searches, an expanded and anatomically comprehensive set of results can be obtained. The broader scientific and publishing communities should consider taking up the challenge of semantically enabled search capabilities.
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- 2016
23. Molecular identification of a peroxidase gene controlling body size in the entomopathogenic nematode Steinernema hermaphroditum
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Schwartz, Hillel T, primary, Tan, Chieh-Hsiang, additional, Peraza, Jackeline, additional, Raymundo, Krystal Louise T, additional, and Sternberg, Paul W, additional
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- 2023
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24. Distinct neurogenetic mechanisms establish the same chemosensory valence state at different life stages in Caenorhabditis elegans
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Banerjee, Navonil, primary, Rojas Palato, Elisa J, additional, Shih, Pei-Yin, additional, Sternberg, Paul W, additional, and Hallem, Elissa A, additional
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- 2023
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25. Molecular identification of a peroxidase gene controlling body size in the entomopathogenic nematodeSteinernema hermaphroditum
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Schwartz, Hillel T T, primary, Tan, Chieh-Hsiang, additional, Peraza, Jackeline, additional, Raymundo, Krystal Louise T, additional, and Sternberg, Paul W, additional
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- 2023
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26. Synaptic polarity of the interneuron circuit controlling C. elegans locomotion
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Rakowski, Franciszek, Srinivasan, Jagan, Sternberg, Paul W., and Karbowski, Jan
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Quantitative Biology - Neurons and Cognition - Abstract
C. elegans is the only animal for which a detailed neural connectivity diagram has been constructed. However, synaptic polarities in this diagram, and thus, circuit functions are largely unknown. Here, we deciphered the likely polarities of 7 pre-motor neurons implicated in the control of worm's locomotion, using a combination of experimental and computational tools. We performed single and multiple laser ablations in the locomotor interneuron circuit and recorded times the worms spent in forward and backward locomotion. We constructed a theoretical model of the locomotor circuit and searched its all possible synaptic polarity combinations and sensory input patterns in order to find the best match to the timing data. The optimal solution is when either all or most of the interneurons are inhibitory and forward interneurons receive the strongest input, which suggests that inhibition governs the dynamics of the locomotor interneuron circuit. From the five pre-motor interneurons, only AVB and AVD are equally likely to be excitatory, i.e. they have probably similar number of inhibitory and excitatory connections to distant targets. The method used here has a general character and thus can be also applied to other neural systems consisting of small functional networks., Comment: Connectivity patterns of neural network controlling C. elegans motion
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- 2014
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27. Comparative genomics of Steinernema reveals deeply conserved gene regulatory networks
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Dillman, Adler R, Macchietto, Marissa, Porter, Camille F, Rogers, Alicia, Williams, Brian, Antoshechkin, Igor, Lee, Ming-Min, Goodwin, Zane, Lu, Xiaojun, Lewis, Edwin E, Goodrich-Blair, Heidi, Stock, S Patricia, Adams, Byron J, Sternberg, Paul W, and Mortazavi, Ali
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Genetics ,Biotechnology ,Human Genome ,Infectious Diseases ,Infection ,Animals ,Caenorhabditis ,Conserved Sequence ,Gene Regulatory Networks ,Genome ,Pest Control ,Biological ,Phylogeny ,Protein Structure ,Tertiary ,Regulatory Sequences ,Nucleic Acid ,Rhabditida ,Symbiosis ,Environmental Sciences ,Biological Sciences ,Information and Computing Sciences ,Bioinformatics - Abstract
BackgroundParasitism is a major ecological niche for a variety of nematodes. Multiple nematode lineages have specialized as pathogens, including deadly parasites of insects that are used in biological control. We have sequenced and analyzed the draft genomes and transcriptomes of the entomopathogenic nematode Steinernema carpocapsae and four congeners (S. scapterisci, S. monticolum, S. feltiae, and S. glaseri).ResultsWe used these genomes to establish phylogenetic relationships, explore gene conservation across species, and identify genes uniquely expanded in insect parasites. Protein domain analysis in Steinernema revealed a striking expansion of numerous putative parasitism genes, including certain protease and protease inhibitor families, as well as fatty acid- and retinol-binding proteins. Stage-specific gene expression of some of these expanded families further supports the notion that they are involved in insect parasitism by Steinernema. We show that sets of novel conserved non-coding regulatory motifs are associated with orthologous genes in Steinernema and Caenorhabditis.ConclusionsWe have identified a set of expanded gene families that are likely to be involved in parasitism. We have also identified a set of non-coding motifs associated with groups of orthologous genes in Steinernema and Caenorhabditis involved in neurogenesis and embryonic development that are likely part of conserved protein-DNA relationships shared between these two genera.
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- 2015
28. Conserved nematode signalling molecules elicit plant defenses and pathogen resistance.
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Manosalva, Patricia, Manohar, Murli, von Reuss, Stephan H, Chen, Shiyan, Koch, Aline, Kaplan, Fatma, Choe, Andrea, Micikas, Robert J, Wang, Xiaohong, Kogel, Karl-Heinz, Sternberg, Paul W, Williamson, Valerie M, Schroeder, Frank C, and Klessig, Daniel F
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Animals ,Nematoda ,Pseudomonas syringae ,Arabidopsis ,Salicylic Acid ,Cyclopentanes ,Pheromones ,Signal Transduction ,Host-Parasite Interactions ,Oxylipins ,Plant Immunity - Abstract
Plant-defense responses are triggered by perception of conserved microbe-associated molecular patterns (MAMPs), for example, flagellin or peptidoglycan. However, it remained unknown whether plants can detect conserved molecular patterns derived from plant-parasitic animals, including nematodes. Here we show that several genera of plant-parasitic nematodes produce small molecules called ascarosides, an evolutionarily conserved family of nematode pheromones. Picomolar to micromolar concentrations of ascr#18, the major ascaroside in plant-parasitic nematodes, induce hallmark defense responses including the expression of genes associated with MAMP-triggered immunity, activation of mitogen-activated protein kinases, as well as salicylic acid- and jasmonic acid-mediated defense signalling pathways. Ascr#18 perception increases resistance in Arabidopsis, tomato, potato and barley to viral, bacterial, oomycete, fungal and nematode infections. These results indicate that plants recognize ascarosides as a conserved molecular signature of nematodes. Using small-molecule signals such as ascarosides to activate plant immune responses has potential utility to improve economic and environmental sustainability of agriculture.
- Published
- 2015
29. Large-field-of-view Chip-scale Talbot-grid-based Fluorescence Microscopy
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Pang, Shuo, Han, Chao, Kato, Mihoko, Sternberg, Paul W., and Yang, Changhuei
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Physics - Optics ,Physics - Biological Physics ,Physics - Instrumentation and Detectors - Abstract
The fluorescence microscope is one of the most important tools in modern clinical diagnosis and biological science. However, its expense, size and limited field-of-view (FOV) are becoming bottlenecks in key applications such as large-scale phenotyping and low-resource-setting diagnostics. Here we report a low-cost, compact chip-scale fluorescence-imaging platform, termed the Fluorescence Talbot Microscopy (FTM), which utilizes the Talbot self-imaging effect to enable efficient fluorescence imaging over a large and directly-scalable FOV. The FTM prototype has a resolution of 1.2 microns and an FOV of 3.9 mm x 3.5 mm. We demonstrate the imaging capability of FTM on fluorescently labeled breast cancer cells (SK-BR-3) and HEK cells expressing green fluorescent protein.
- Published
- 2012
30. CRISPR required for host colonization
- Author
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Veesenmeyer, Jeff L, Andersen, Aaron W, Lu, Xiaojun, Hussa, Elizabeth A, Murfin, Kristen E, Chaston, John M, Dillman, Adler R, Wassarman, Karen M, Sternberg, Paul W, and Goodrich‐Blair, Heidi
- Subjects
Microbiology ,Biological Sciences ,Infectious Diseases ,Genetics ,Digestive Diseases ,Animals ,Bacterial Proteins ,Base Sequence ,Clustered Regularly Interspaced Short Palindromic Repeats ,DNA Transposable Elements ,Intestines ,Molecular Sequence Data ,Mutagenesis ,Insertional ,RNA ,Bacterial ,Rhabditida ,Symbiosis ,Xenorhabdus ,Agricultural and Veterinary Sciences ,Medical and Health Sciences ,Biological sciences - Abstract
The bacterium Xenorhabdus nematophila is a mutualist of entomopathogenic Steinernema carpocapsae nematodes and facilitates infection of insect hosts. X. nematophila colonizes the intestine of S. carpocapsae which carries it between insects. In the X. nematophila colonization-defective mutant nilD6::Tn5, the transposon is inserted in a region lacking obvious coding potential. We demonstrate that the transposon disrupts expression of a single CRISPR RNA, NilD RNA. A variant NilD RNA also is expressed by X. nematophila strains from S. anatoliense and S. websteri nematodes. Only nilD from the S. carpocapsae strain of X. nematophila rescued the colonization defect of the nilD6::Tn5 mutant, and this mutant was defective in colonizing all three nematode host species. NilD expression depends on the presence of the associated Cas6e but not Cas3, components of the Type I-E CRISPR-associated machinery. While cas6e deletion in the complemented strain abolished nematode colonization, its disruption in the wild-type parent did not. Likewise, nilD deletion in the parental strain did not impact colonization of the nematode, revealing that the requirement for NilD is evident only in certain genetic backgrounds. Our data demonstrate that NilD RNA is conditionally necessary for mutualistic host colonization and suggest that it functions to regulate endogenous gene expression.
- Published
- 2014
31. Comparative validation of the D. melanogaster modENCODE transcriptome annotation
- Author
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Chen, Zhen-Xia, Sturgill, David, Qu, Jiaxin, Jiang, Huaiyang, Park, Soo, Boley, Nathan, Suzuki, Ana Maria, Fletcher, Anthony R, Plachetzki, David C, FitzGerald, Peter C, Artieri, Carlo G, Atallah, Joel, Barmina, Olga, Brown, James B, Blankenburg, Kerstin P, Clough, Emily, Dasgupta, Abhijit, Gubbala, Sai, Han, Yi, Jayaseelan, Joy C, Kalra, Divya, Kim, Yoo-Ah, Kovar, Christie L, Lee, Sandra L, Li, Mingmei, Malley, James D, Malone, John H, Mathew, Tittu, Mattiuzzo, Nicolas R, Munidasa, Mala, Muzny, Donna M, Ongeri, Fiona, Perales, Lora, Przytycka, Teresa M, Pu, Ling-Ling, Robinson, Garrett, Thornton, Rebecca L, Saada, Nehad, Scherer, Steven E, Smith, Harold E, Vinson, Charles, Warner, Crystal B, Worley, Kim C, Wu, Yuan-Qing, Zou, Xiaoyan, Cherbas, Peter, Kellis, Manolis, Eisen, Michael B, Piano, Fabio, Kionte, Karin, Fitch, David H, Sternberg, Paul W, Cutter, Asher D, Duff, Michael O, Hoskins, Roger A, Graveley, Brenton R, Gibbs, Richard A, Bickel, Peter J, Kopp, Artyom, Carninci, Piero, Celniker, Susan E, Oliver, Brian, and Richards, Stephen
- Subjects
Biological Sciences ,Bioinformatics and Computational Biology ,Genetics ,Human Genome ,Biotechnology ,Generic health relevance ,Animals ,Cluster Analysis ,Computational Biology ,Drosophila melanogaster ,Evolution ,Molecular ,Exons ,Female ,Gene Expression Profiling ,Genome ,Insect ,Humans ,Male ,Molecular Sequence Annotation ,Nucleotide Motifs ,Phylogeny ,Position-Specific Scoring Matrices ,Promoter Regions ,Genetic ,RNA Editing ,RNA Splice Sites ,RNA Splicing ,Reproducibility of Results ,Transcription Initiation Site ,Transcriptome ,Medical and Health Sciences ,Bioinformatics - Abstract
Accurate gene model annotation of reference genomes is critical for making them useful. The modENCODE project has improved the D. melanogaster genome annotation by using deep and diverse high-throughput data. Since transcriptional activity that has been evolutionarily conserved is likely to have an advantageous function, we have performed large-scale interspecific comparisons to increase confidence in predicted annotations. To support comparative genomics, we filled in divergence gaps in the Drosophila phylogeny by generating draft genomes for eight new species. For comparative transcriptome analysis, we generated mRNA expression profiles on 81 samples from multiple tissues and developmental stages of 15 Drosophila species, and we performed cap analysis of gene expression in D. melanogaster and D. pseudoobscura. We also describe conservation of four distinct core promoter structures composed of combinations of elements at three positions. Overall, each type of genomic feature shows a characteristic divergence rate relative to neutral models, highlighting the value of multispecies alignment in annotating a target genome that should prove useful in the annotation of other high priority genomes, especially human and other mammalian genomes that are rich in noncoding sequences. We report that the vast majority of elements in the annotation are evolutionarily conserved, indicating that the annotation will be an important springboard for functional genetic testing by the Drosophila community.
- Published
- 2014
32. A Modified Mole Cricket Lure and Description of Scapteriscus borellii (Orthoptera: Gryllotalpidae) Range Expansion and Calling Song in California
- Author
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Dillman, Adler R, Cronin, Christopher J, Tang, Joseph, Gray, David A, and Sternberg, Paul W
- Subjects
Zoology ,Ecology ,Biological Sciences ,Animal Communication ,Animal Distribution ,Animals ,California ,Entomology ,Female ,Gryllidae ,Male ,Scapteriscus borellii ,mole cricket ,cricket trap ,calling song - Abstract
Invasive mole cricket species in the genus Scapteriscus have become significant agricultural pests and are continuing to expand their range in North America. Though largely subterranean, adults of some species, such as Scapteriscus borellii Giglio-Tos 1894, are capable of long dispersive flights and phonotaxis to male calling songs to find suitable habitats and mates. Mole crickets in the genus Scapteriscus are known to be attracted to and can be caught by audio lure traps that broadcast synthesized or recorded calling songs. We report improvements in the design and production of electronic controllers for the automation of semipermanent mole cricket trap lures as well as highly portable audio trap collection designs. Using these improved audio lure traps, we collected the first reported individuals of the pest mole cricket S. borellii in California. We describe several characteristic features of the calling song of the California population including that the pulse rate is a function of soil temperature, similar to Florida populations of S. borellii. Further, we show that other calling song characteristics (carrier frequency, intensity, and pulse rate) are significantly different between the populations.
- Published
- 2014
33. Microsporidia-nematode associations in methane seeps reveal basal fungal parasitism in the deep sea.
- Author
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Sapir, Amir, Dillman, Adler R, Connon, Stephanie A, Grupe, Benjamin M, Ingels, Jeroen, Mundo-Ocampo, Manuel, Levin, Lisa A, Baldwin, James G, Orphan, Victoria J, and Sternberg, Paul W
- Subjects
basal fungi in the deep sea ,deep-sea methane seeps ,deep-sea microsporidia parasitism ,muscle decomposition ,nematodes hosts ,Infectious Diseases ,2.2 Factors relating to the physical environment ,Infection ,Environmental Science and Management ,Soil Sciences ,Microbiology - Abstract
The deep sea is Earth's largest habitat but little is known about the nature of deep-sea parasitism. In contrast to a few characterized cases of bacterial and protistan parasites, the existence and biological significance of deep-sea parasitic fungi is yet to be understood. Here we report the discovery of a fungus-related parasitic microsporidium, Nematocenator marisprofundi n. gen. n. sp. that infects benthic nematodes at methane seeps on the Pacific Ocean floor. This infection is species-specific and has been temporally and spatially stable over 2 years of sampling, indicating an ecologically consistent host-parasite interaction. A high distribution of spores in the reproductive tracts of infected males and females and their absence from host nematodes' intestines suggests a sexual transmission strategy in contrast to the fecal-oral transmission of most microsporidia. N. marisprofundi targets the host's body wall muscles causing cell lysis, and in severe infection even muscle filament degradation. Phylogenetic analyses placed N. marisprofundi in a novel and basal clade not closely related to any described microsporidia clade, suggesting either that microsporidia-nematode parasitism occurred early in microsporidia evolution or that host specialization occurred late in an ancient deep-sea microsporidian lineage. Our findings reveal that methane seeps support complex ecosystems involving interkingdom interactions between bacteria, nematodes, and parasitic fungi and that microsporidia parasitism exists also in the deep-sea biosphere.
- Published
- 2014
34. Enrichment on steps, not genes, improves inference of differentially expressed pathways.
- Author
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Markarian, Nicholas, Van Auken, Kimberly M., Ebert, Dustin, and Sternberg, Paul W.
- Abstract
Enrichment analysis is frequently used in combination with differential expression data to investigate potential commonalities amongst lists of genes and generate hypotheses for further experiments. However, current enrichment analysis approaches on pathways ignore the functional relationships between genes in a pathway, particularly OR logic that occurs when a set of proteins can each individually perform the same step in a pathway. As a result, these approaches miss pathways with large or multiple sets because of an inflation of pathway size (when measured as the total gene count) relative to the number of steps. We address this problem by enriching on step-enabling entities in pathways. We treat sets of protein-coding genes as single entities, and we also weight sets to account for the number of genes in them using the multivariate Fisher's noncentral hypergeometric distribution. We then show three examples of pathways that are recovered with this method and find that the results have significant proportions of pathways not found in gene list enrichment analysis. Author summary: Genome-scale experiments typically identify sets of genes which are primarily analyzed by enrichment analysis to identify relevant pathways that may be perturbed. Curated pathway models have rich structure that we believe can be exploited to get better results. Some pathway steps are enabled by sets of interchangeable genes which inflate the gene count of their respective pathways relative to the number of steps. We improve sensitivity towards these pathways in enrichment analysis by performing enrichment on steps. We then use this approach to identify pathways that would otherwise be missed in medically relevant datasets to gain new insights. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
35. Fluorescence dynamics of lysosomal-related organelle flashing in the intestinal cells ofCaenorhabditis elegans
- Author
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Tan, Chieh-Hsiang, primary, Ding, Keke, additional, Zhang, Mark G, additional, and Sternberg, Paul W., additional
- Published
- 2023
- Full Text
- View/download PDF
36. Split cGAL, an intersectional strategy using a split intein for refined spatiotemporal transgene control in Caenorhabditis elegans
- Author
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Wang, Han, Liu, Jonathan, Yuet, Kai P., Hill, Andrew J., and Sternberg, Paul W.
- Published
- 2018
37. Reconstructing a metazoan genetic pathway with transcriptome-wide epistasis measurements
- Author
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Angeles-Albores, David, Robinson, Carmie Puckett, Williams, Brian A., Wold, Barbara J., and Sternberg, Paul W.
- Published
- 2018
38. Elucidating the molecular and developmental biology of parasitic nematodes: Moving to a multiomics paradigm
- Author
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Ma, Guangxu, primary, Wang, Tao, additional, Korhonen, Pasi K., additional, Hofmann, Andreas, additional, Sternberg, Paul W., additional, Young, Neil D., additional, and Gasser, Robin B., additional
- Published
- 2020
- Full Text
- View/download PDF
39. Systems level circuit model of C. elegans undulatory locomotion: mathematical modeling and molecular genetics
- Author
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Karbowski, Jan, Schindelman, Gary, Cronin, Chris J., Seah, Adeline, and Sternberg, Paul W.
- Subjects
Quantitative Biology - Neurons and Cognition ,Quantitative Biology - Genomics - Abstract
To establish the relationship between locomotory behavior and dynamics of neural circuits in the nematode C. elegans we combined molecular and theoretical approaches. In particular, we quantitatively analyzed the motion of C. elegans with defective synaptic GABA and acetylcholine transmission, defective muscle calcium signaling, and defective muscles and cuticle structures, and compared the data with our systems level circuit model. The major experimental findings are: (i) anterior-to-posterior gradients of body bending flex for almost all strains both for forward and backward motion, and for neuronal mutants, also analogous weak gradients of undulatory frequency, (ii) existence of some form of neuromuscular (stretch receptor) feedback, (iii) invariance of neuromuscular wavelength, (iv) biphasic dependence of frequency on synaptic signaling, and (v) decrease of frequency with increase of the muscle time constant. Based on (i) we hypothesize that the Central Pattern Generator (CPG) is located in the head both for forward and backward motion. Points (i) and (ii) are the starting assumptions for our theoretical model, whose dynamical patterns are qualitatively insensitive to the details of the CPG design if stretch receptor feedback is sufficiently strong and slow. The model reveals that stretch receptor coupling in the body wall is critical for generation of the neuromuscular wave. Our model agrees with our behavioral data(iii), (iv), and (v), and with other pertinent published data, e.g., that frequency is an increasing function of muscle gap-junction coupling., Comment: Neural control of C. elegans motion with genetic perturbations
- Published
- 2007
40. FMRFamide-like peptides expand the behavioral repertoire of a densely connected nervous system
- Author
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Lee, James Siho, Shih, Pei-Yin, Schaedel, Oren N., Quintero-Cadena, Porfirio, Rogers, Alicia K., and Sternberg, Paul W.
- Published
- 2017
41. Conservation rules, their breakdown, and optimality in Caenorhabditis sinusoidal locomotion
- Author
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Karbowski, Jan, Cronin, Christopher J., Seah, Adeline, Mendel, Jane E., Cleary, Daniel, and Sternberg, Paul W.
- Subjects
Quantitative Biology - Neurons and Cognition ,Quantitative Biology - Genomics - Abstract
Undulatory locomotion is common to nematodes as well as to limbless vertebrates, but its control is not understood in spite of the identification of hundred of genes involved in Caenorhabditis elegans locomotion. To reveal the mechanisms of nematode undulatory locomotion, we quantitatively analyzed the movement of C. elegans with genetic perturbations to neurons, muscles, and skeleton (cuticle). We also compared locomotion of different Caenorhabditis species. We constructed a theoretical model that combines mechanics and biophysics, and that is constrained by the observations of propulsion and muscular velocities, as well as wavelength and amplitude of undulations. We find that normalized wavelength is a conserved quantity among wild-type C. elegans individuals, across mutants, and across different species. The velocity of forward propulsion scales linearly with the velocity of the muscular wave and the corresponding slope is also a conserved quantity and almost optimal; the exceptions are in some mutants affecting cuticle structure. In theoretical terms, the optimality of the slope is equivalent to the exact balance between muscular and visco-elastic body reaction bending moments. We find that the amplitude and frequency of undulations are inversely correlated and provide a theoretical explanation for this fact. These experimental results are valid both for young adults and for all larval stages of wild type C. elegans. In particular, during development, the amplitude scales linearly with the wavelength, consistent with our theory. We also investigated the influence of substrate firmness on motion parameters, and found that it does not affect the above invariants. In general, our biomechanical model can explain the observed robustness of the mechanisms controlling nematode undulatory locomotion., Comment: Journal of Theoretical Biology, in press
- Published
- 2006
42. The draft genome and transcriptome of Panagrellus redivivus are shaped by the harsh demands of a free-living lifestyle.
- Author
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Srinivasan, Jagan, Dillman, Adler R, Macchietto, Marissa G, Heikkinen, Liisa, Lakso, Merja, Fracchia, Kelley M, Antoshechkin, Igor, Mortazavi, Ali, Wong, Garry, and Sternberg, Paul W
- Subjects
Animals ,Rhabditida ,Ubiquitin-Protein Ligases ,Cullin Proteins ,Helminth Proteins ,MicroRNAs ,RNA Precursors ,Sequence Analysis ,DNA ,Environment ,Evolution ,Molecular ,Phylogeny ,Cell Death ,RNA Interference ,Genome ,Helminth ,Transcriptome ,Evolution ,Molecular ,Genome ,Helminth ,Sequence Analysis ,DNA ,Genetics ,Developmental Biology - Abstract
Nematodes compose an abundant and diverse invertebrate phylum with members inhabiting nearly every ecological niche. Panagrellus redivivus (the "microworm") is a free-living nematode frequently used to understand the evolution of developmental and behavioral processes given its phylogenetic distance to Caenorhabditis elegans. Here we report the de novo sequencing of the genome, transcriptome, and small RNAs of P. redivivus. Using a combination of automated gene finders and RNA-seq data, we predict 24,249 genes and 32,676 transcripts. Small RNA analysis revealed 248 microRNA (miRNA) hairpins, of which 63 had orthologs in other species. Fourteen miRNA clusters containing 42 miRNA precursors were found. The RNA interference, dauer development, and programmed cell death pathways are largely conserved. Analysis of protein family domain abundance revealed that P. redivivus has experienced a striking expansion of BTB domain-containing proteins and an unprecedented expansion of the cullin scaffold family of proteins involved in multi-subunit ubiquitin ligases, suggesting proteolytic plasticity and/or tighter regulation of protein turnover. The eukaryotic release factor protein family has also been dramatically expanded and suggests an ongoing evolutionary arms race with viruses and transposons. The P. redivivus genome provides a resource to advance our understanding of nematode evolution and biology and to further elucidate the genomic architecture leading to free-living lineages, taking advantage of the many fascinating features of this worm revealed by comparative studies.
- Published
- 2013
43. Origin and Evolution of Dishevelled
- Author
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Dillman, Adler R, Minor, Paul J, and Sternberg, Paul W
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Underpinning research ,1.1 Normal biological development and functioning ,Generic health relevance ,Adaptor Proteins ,Signal Transducing ,Animals ,Caenorhabditis ,Dishevelled Proteins ,Evolution ,Molecular ,Invertebrates ,Nematoda ,Phosphoproteins ,Phosphorylation ,Phylogeny ,Protein Isoforms ,Protein Structure ,Tertiary ,RNA Splicing ,Signal Transduction ,Wnt Proteins ,dishevelled ,protein evolution ,Wnt ,C. elegans ,Genetics ,Biochemistry and cell biology ,Statistics - Abstract
Dishevelled (Dsh or Dvl) is an important signaling protein, playing a key role in Wnt signaling and relaying cellular information for several developmental pathways. Dsh is highly conserved among metazoans and has expanded into a multigene family in most bilaterian lineages, including vertebrates, planarians, and nematodes. These orthologs, where explored, are known to have considerable overlap in function, but evidence for functional specialization continues to mount. We performed a comparative analysis of Dsh across animals to explore protein architecture and identify conserved and divergent features that could provide insight into functional specialization with an emphasis on invertebrates, especially nematodes. We find evidence of dynamic evolution of Dsh, particularly among nematodes, with taxa varying in ortholog number from one to three. We identify a new domain specific to some nematode lineages and find an unexpected nuclear localization signal conserved in many Dsh orthologs. Our findings raise questions of protein evolution in general and provide clues as to how animals have dealt with the complex intricacies of having a protein, such as Dsh, act as a central messenger hub connected to many different and vitally important pathways. We discuss our findings in the context of functional specialization and bring many testable hypotheses to light.
- Published
- 2013
44. The genome and developmental transcriptome of the strongylid nematode Haemonchus contortus
- Author
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Schwarz, Erich M, Korhonen, Pasi K, Campbell, Bronwyn E, Young, Neil D, Jex, Aaron R, Jabbar, Abdul, Hall, Ross S, Mondal, Alinda, Howe, Adina C, Pell, Jason, Hofmann, Andreas, Boag, Peter R, Zhu, Xing-Quan, Gregory, T Ryan, Loukas, Alex, Williams, Brian A, Antoshechkin, Igor, Brown, C Titus, Sternberg, Paul W, and Gasser, Robin B
- Subjects
Veterinary Sciences ,Agricultural ,Veterinary and Food Sciences ,Biological Sciences ,Genetics ,Biotechnology ,Immunization ,Orphan Drug ,Human Genome ,Rare Diseases ,Infectious Diseases ,Vaccine Related ,Biodefense ,Prevention ,Infection ,Animals ,Anthelmintics ,Antigens ,Helminth ,Drug Resistance ,Female ,Gene Expression Regulation ,Genes ,Helminth ,Genome Size ,Genome ,Helminth ,Haemonchiasis ,Haemonchus ,Helminth Proteins ,Host-Parasite Interactions ,Life Cycle Stages ,Male ,Peptide Hydrolases ,Sheep ,Sheep Diseases ,Transcriptome ,Environmental Sciences ,Information and Computing Sciences ,Bioinformatics - Abstract
BackgroundThe barber's pole worm, Haemonchus contortus, is one of the most economically important parasites of small ruminants worldwide. Although this parasite can be controlled using anthelmintic drugs, resistance against most drugs in common use has become a widespread problem. We provide a draft of the genome and the transcriptomes of all key developmental stages of H. contortus to support biological and biotechnological research areas of this and related parasites.ResultsThe draft genome of H. contortus is 320 Mb in size and encodes 23,610 protein-coding genes. On a fundamental level, we elucidate transcriptional alterations taking place throughout the life cycle, characterize the parasite's gene silencing machinery, and explore molecules involved in development, reproduction, host-parasite interactions, immunity, and disease. The secretome of H. contortus is particularly rich in peptidases linked to blood-feeding activity and interactions with host tissues, and a diverse array of molecules is involved in complex immune responses. On an applied level, we predict drug targets and identify vaccine molecules.ConclusionsThe draft genome and developmental transcriptome of H. contortus provide a major resource to the scientific community for a wide range of genomic, genetic, proteomic, metabolomic, evolutionary, biological, ecological, and epidemiological investigations, and a solid foundation for biotechnological outcomes, including new anthelmintics, vaccines and diagnostic tests. This first draft genome of any strongylid nematode paves the way for a rapid acceleration in our understanding of a wide range of socioeconomically important parasites of one of the largest nematode orders.
- Published
- 2013
45. Genome-Wide Prediction of C. elegans Genetic Interactions
- Author
-
Zhong, Weiwei and Sternberg, Paul W.
- Published
- 2006
46. Whipworm kinomes reflect a unique biology and adaptation to the host animal
- Author
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Stroehlein, Andreas J., Young, Neil D., Korhonen, Pasi K., Chang, Bill C.H., Nejsum, Peter, Pozio, Edoardo, La Rosa, Giuseppe, Sternberg, Paul W., and Gasser, Robin B.
- Published
- 2017
- Full Text
- View/download PDF
47. Worm Phenotype Ontology: integrating phenotype data within and beyond the C. elegans community
- Author
-
Schindelman, Gary, Fernandes, Jolene S, Bastiani, Carol A, Yook, Karen, and Sternberg, Paul W
- Abstract
Abstract Background Caenorhabditis elegans gene-based phenotype information dates back to the 1970's, beginning with Sydney Brenner and the characterization of behavioral and morphological mutant alleles via classical genetics in order to understand nervous system function. Since then C. elegans has become an important genetic model system for the study of basic biological and biomedical principles, largely through the use of phenotype analysis. Because of the growth of C. elegans as a genetically tractable model organism and the development of large-scale analyses, there has been a significant increase of phenotype data that needs to be managed and made accessible to the research community. To do so, a standardized vocabulary is necessary to integrate phenotype data from diverse sources, permit integration with other data types and render the data in a computable form. Results We describe a hierarchically structured, controlled vocabulary of terms that can be used to standardize phenotype descriptions in C. elegans, namely the Worm Phenotype Ontology (WPO). The WPO is currently comprised of 1,880 phenotype terms, 74% of which have been used in the annotation of phenotypes associated with greater than 18,000 C. elegans genes. The scope of the WPO is not exclusively limited to C. elegans biology, rather it is devised to also incorporate phenotypes observed in related nematode species. We have enriched the value of the WPO by integrating it with other ontologies, thereby increasing the accessibility of worm phenotypes to non-nematode biologists. We are actively developing the WPO to continue to fulfill the evolving needs of the scientific community and hope to engage researchers in this crucial endeavor. Conclusions We provide a phenotype ontology (WPO) that will help to facilitate data retrieval, and cross-species comparisons within the nematode community. In the larger scientific community, the WPO will permit data integration, and interoperability across the different Model Organism Databases (MODs) and other biological databases. This standardized phenotype ontology will therefore allow for more complex data queries and enhance bioinformatic analyses.
- Published
- 2011
48. Transcriptional Network Underlying Caenorhabditis elegans Vulval Development
- Author
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Inoue, Takao, Wang, Minqin, Ririe, Ted O., Fernandes, Jolene S., Sternberg, Paul W., and Davidson, Eric H.
- Published
- 2005
49. Genome Annotation by High-Throughput 5′ RNA End Determination
- Author
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Hwang, Byung Joon, Müller, Hans-Michael, Sternberg, Paul W., and Green, Philip P.
- Published
- 2004
50. Transcriptional profiling of trait deterioration in the insect pathogenic nematode Heterorhabditis bacteriophora.
- Author
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Adhikari, Bishwo N, Lin, Chin-Yo, Bai, Xiaodong, Ciche, Todd A, Grewal, Parwinder S, Dillman, Adler R, Chaston, John M, Shapiro-Ilan, David I, Bilgrami, Anwar L, Gaugler, Randy, Sternberg, Paul W, and Adams, Byron J
- Subjects
Animals ,Rhabditoidea ,RNA ,Helminth ,Gene Expression Profiling ,Pest Control ,Biological ,Signal Transduction ,Quantitative Trait ,Heritable ,Expressed Sequence Tags ,RNA ,Helminth ,Pest Control ,Biological ,Quantitative Trait ,Heritable ,Biological Sciences ,Information and Computing Sciences ,Medical and Health Sciences ,Bioinformatics - Abstract
BackgroundThe success of a biological control agent depends on key traits, particularly reproductive potential, environmental tolerance, and ability to be cultured. These traits can deteriorate rapidly when the biological control agent is reared in culture. Trait deterioration under laboratory conditions has been widely documented in the entomopathogenic nematode (EPN) Heterorhabditis bacteriophora (Hb) but the specific mechanisms behind these genetic processes remain unclear. This research investigates the molecular mechanisms of trait deterioration of two experimental lines of Hb, an inbred line (L5M) and its original parental line (OHB). We generated transcriptional profiles of two experimental lines of Hb, identified the differentially expressed genes (DEGs) and validated their differential expression in the deteriorated line.ResultsAn expression profiling study was performed between experimental lines L5M and OHB of Hb with probes for 15,220 ESTs from the Hb transcriptome. Microarray analysis showed 1,185 DEGs comprising of 469 down- and 716 up-regulated genes in trait deteriorated nematodes. Analysis of the DEGs showed that trait deterioration involves massive changes of the transcripts encoding enzymes involved in metabolism, signal transduction, virulence and longevity. We observed a pattern of reduced expression of enzymes related to primary metabolic processes and induced secondary metabolism. Expression of sixteen DEGs in trait deteriorated nematodes was validated by quantitative reverse transcription-PCR (qRT-PCR) which revealed similar expression kinetics for all the genes tested as shown by microarray.ConclusionAs the most closely related major entomopathogen to C. elegans, Hb provides an attractive near-term application for using a model organism to better understand interspecies interactions and to enhance our understanding of the mechanisms underlying trait deterioration in biological control agents. This information could also be used to improve the beneficial traits of biological control agents and better understand fundamental aspects of nematode parasitism and mutualism.
- Published
- 2009
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