scholarly journals An integrated analysis tool reveals intrinsic biases in gene set enrichment

2021 ◽  
Author(s):  
Nishant Thakur ◽  
Nathalie Pujol ◽  
Jacques van Helden ◽  
Robert H Waterston ◽  
LaDeana W Hillier ◽  
...  
Keyword(s):  
Large Scale ◽  
Model Organism ◽  
Integrated Analysis ◽  
Analysis Tool ◽  
Gene Set Enrichment ◽  
Phylogenetic Conservation ◽  
C Elegans ◽  
Gene Enrichment ◽  
Depth Study ◽  
The Universe

Generating meaningful interpretations of gene lists remains a challenge for all large-scale studies. Many approaches exist, often based on evaluating gene enrichment among pre-determined gene classes. Here, we conceived and implemented yet another analysis tool (YAAT), specifically for data from the widely-used model organism C. elegans. YAAT extends standard enrichment analyses, using a combination of co-expression data and profiles of phylogenetic conservation, to identify groups of functionally-related genes. It additionally allows class clustering, providing inference of functional links between groups of genes. We give examples of the utility of YAAT for uncovering unsuspected links between genes and show how the approach can be used to prioritise genes for in-depth study. Our analyses revealed several limitations to the meaningful interpretation of gene lists, specifically related to data sources and the "universe" of gene lists used. We hope that YAAT will represent a model for integrated analysis that could be useful for large-scale exploration of biological function in other species.

scholarly journals HeALTH: An Automated Platform for Long-term Longitudinal Studies of Whole Organisms under Precise Environmental Control

2019 ◽  
Author(s):  
Kim N. Le ◽  
Mei Zhan ◽  
Yongmin Cho ◽  
Jason Wan ◽  
Dhaval S. Patel ◽  
...  
Keyword(s):  
Aging Process ◽  
Large Scale ◽  
Environmental Control ◽  
Model Organism ◽  
Model Systems ◽  
Aging Research ◽  
C Elegans ◽  
Environmental Perturbations ◽  
Automated Platform

ABSTRACTHealth and longevity in all organisms are strongly influenced by the environment. To fully understand how environmental factors interact with genetic and stochastic factors to modulate the aging process, it is crucial to precisely control environmental conditions for long-term studies. In the commonly used model organism Caenorhabditis elegans, existing assays for healthspan and lifespan have inherent limitations, making it difficult to perform large-scale, longitudinal aging studies under precise environmental control. To address this constraint, we developed the Health and Lifespan Testing Hub (HeALTH), an automated, microfluidic-based system for robust, long-term, longitudinal behavioral monitoring. Our system provides spatiotemporal environmental control. We demonstrate health and lifespan studies under a variety of genetic and environmental perturbations while observing how individuality plays a role in the aging process. This system is generalizable beyond aging research for C. elegans, particularly for short- or long-term behavioral assays, and is also possible to be adapted for other model systems.

C. elegans models of neuromuscular diseases expedite translational research

2010 ◽  
Vol 1 (3) ◽  
Author(s):  
James Sleigh ◽  
David Sattelle
Keyword(s):  
Large Scale ◽  
Genetic Model ◽  
Muscular Atrophy ◽  
Neuromuscular Disorders ◽  
Neuromuscular Diseases ◽  
Model Organism ◽  
Disease Genes ◽  
Chemical Library ◽  
C Elegans

AbstractThe nematode Caenorhabditis elegans is a genetic model organism and the only animal with a complete nervous system wiring diagram. With only 302 neurons and 95 striated muscle cells, a rich array of mutants with defective locomotion and the facility for individual targeted gene knockdown by RNA interference, it lends itself to the exploration of gene function at nerve muscle junctions. With approximately 60% of human disease genes having a C. elegans homologue, there is growing interest in the deployment of lowcost, high-throughput, drug screens of nematode transgenic and mutant strains mimicking aspects of the pathology of devastating human neuromuscular disorders. Here we explore the contributions already made by C. elegans to our understanding of muscular dystrophies (Duchenne and Becker), spinal muscular atrophy, amyotrophic lateral sclerosis, Friedreich’s ataxia, inclusion body myositis and the prospects for contributions to other neuromuscular disorders. A bottleneck to low-cost, in vivo, large-scale chemical library screening for new candidate therapies has been rapid, automated, behavioural phenotyping. Recent progress in quantifying simple swimming (thrashing) movements is making such screening possible and is expediting the translation of drug candidates towards the clinic.

scholarly journals Comparative genomics of ten new Caenorhabditis species

2018 ◽  
Author(s):  
Lewis Stevens ◽  
Marie-Anne Félix ◽  
Toni Beltran ◽  
Christian Braendle ◽  
Carlos Caurcel ◽  
...  
Keyword(s):  
New Species ◽  
Large Scale ◽  
Transcriptome Assembly ◽  
Draft Genome ◽  
Model Organism ◽  
Present Species ◽  
C Elegans ◽  
Genome Data ◽  
Evolutionary Origins ◽  
Caenorhabditis Species

AbstractThe nematode Caenorhabditis elegans has been central to the understanding of metazoan biology. However, C. elegans is but one species among millions and the significance of this important model organism will only be fully revealed if it is placed in a rich evolutionary context. Global sampling efforts have led to the discovery of over 50 putative species from the genus Caenorhabditis, many of which await formal species description. Here, we present species descriptions for ten new Caenorhabditis species. We also present draft genome sequences for nine of these new species, along with a transcriptome assembly for one. We exploit these whole-genome data to reconstruct the Caenorhabditis phylogeny and use this phylogenetic tree to dissect the evolution of morphology in the genus. We show unexpected complexity in the evolutionary history of key developmental pathway genes. The genomic data also permit large scale analysis of gene structure, which we find to be highly variable within the genus. These new species and the associated genomic resources will be essential in our attempts to understand the evolutionary origins of the C. elegans model.

Identification of key mRNAs, miRNAs, and mRNA-miRNA network involved in papillary thyroid carcinoma

2020 ◽  
Vol 15 ◽  
Author(s):  
Wei Han ◽  
Dongchen Lu ◽  
Chonggao Wang ◽  
Mengdi Cui ◽  
Kai Lu
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Differential Expression Analysis ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Integrated Analysis ◽  
Papillary Thyroid ◽  
Gene Set Enrichment ◽  
Mirna Expression Data

Background: In the past decades, the incidence of thyroid cancer (TC) has been gradually increasing, owing to the widespread use of ultrasound scanning devices. However, the key mRNAs, miRNAs, and mRNA-miRNA network in papillary thyroid carcinoma (PTC) has not been fully understood. Material and Methods: In this study, multiple bioinformatics methods were employed, including differential expression analysis, gene set enrichment analysis, and miRNA-mRNA interaction network construction. Results: First, we investigated the key miRNAs that regulated significantly more differentially expressed genes based on GSEA method. Second, we searched for the key miRNAs based on the mRNA-miRNA interaction subnetwork involved in PTC. We identified hsa-mir-1275, hsa-mir-1291, hsa-mir-206 and hsa-mir-375 as the key miRNAs involved in PTC pathogenesis. Conclusion: The integrated analysis of the gene and miRNA expression data not only identified key mRNAs, miRNAs, and mRNA-miRNA network involved in papillary thyroid carcinoma, but also improved our understanding of the pathogenesis of PTC.

Cosmological spacetimes

2018 ◽  
Author(s):  
Nathalie Deruelle ◽  
Jean-Philippe Uzan
Keyword(s):  
Cosmological Model ◽  
Large Scale ◽  
Cosmic Time ◽  
De Sitter ◽  
Matter Distribution ◽  
Observable Universe ◽  
Cosmological Principle ◽  
Riemannian Spacetime ◽  
The Universe ◽  
Copernican Principle

This chapter provides a few examples of representations of the universe on a large scale—a first step in constructing a cosmological model. It first discusses the Copernican principle, which is an approximation/hypothesis about the matter distribution in the observable universe. The chapter then turns to the cosmological principle—a hypothesis about the geometry of the Riemannian spacetime representing the universe, which is assumed to be foliated by 3-spaces labeled by a cosmic time t which are homogeneous and isotropic, that is, ‘maximally symmetric’. After a discussion on maximally symmetric space, this chapter considers spacetimes with homogenous and isotropic sections. Finally, this chapter discusses Milne and de Sitter spacetimes.

The Nature of Time

2018 ◽  
Author(s):  
Donald C. Williams
Keyword(s):  
Large Scale ◽  
Time Travel ◽  
Dimensional Manifold ◽  
Nature Of Time ◽  
Manifold Theory ◽  
The Universe ◽  
Theoretical Cost ◽  
Do So

This chapter provides a fuller treatment of the pure manifold theory with an expanded discussion of competing doctrines. It is argued that competing doctrines fail to account for the extensive and/or transitory aspect(s) of time, or they do so at great theoretical cost. The pure manifold theory accounts for the extensive aspect of time because it admits a four-dimensional manifold and it accounts for the transitory aspect of time because it hypothesizes that the increase of entropy is the thing that is ‘felt’ in veridical cases of felt passage. A four-dimensionalist theory of time travel is outlined, along with a sketch of large-scale cosmological traits of the universe.

scholarly journals Large-Scale Flows in the Local Universe

1996 ◽  
Vol 168 ◽  
pp. 175-182 ◽  
Author(s):  
D.S. Mathewson ◽  
V.L. Ford
Keyword(s):  
Large Scale ◽  
Velocity Measurements ◽  
Local Universe ◽  
Peculiar Velocities ◽  
Redshift Surveys ◽  
Density Maps ◽  
The Universe ◽  
Great Wall ◽  
Great Attractor ◽  
Streaming Flow

Peculiar velocity measurements of 2500 southern spiral galaxies show large-scale flows in the direction of the Hydra-Centaurus clusters which fully participate in the flow themselves. The flow is not uniform over this region and seems to be associated with the denser regions which participate in the flow of amplitude about 400km/s. In the less dense regions the flow is small or non-existent. This makes the flow quite asymmetric and inconsistent with that expected from large-scale, parallel streaming flow that includes all galaxies out to 6000km/s as previously thought. The flow cannot be modelled by a Great Attractor at 4300km/s or the Centaurus clusters at 3500km/s. Indeed, from the density maps derived from the redshift surveys of “optical” and IRAS galaxies, it is difficult to see how the mass concentrations can be responsible particularly as they themselves participate in the flow. These results bring into question the generally accepted reason for the peculiar velocities of galaxies that they arise solely as a consequence of infall into the dense regions of the universe. To the N. of the Great Attractor region, the flow increases and shows no sign of diminishing out to the redshift limit of 8000km/s in this direction. We may have detected flow in the nearest section of the Great Wall.

scholarly journals PRISMS-Fatigue computational framework for fatigue analysis in polycrystalline metals and alloys

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Mohammadreza Yaghoobi ◽  
Krzysztof S. Stopka ◽  
Aaditya Lakshmanan ◽  
Veera Sundararaghavan ◽  
John E. Allison ◽  
...  
Keyword(s):  
Open Source ◽  
Open Source Software ◽  
Large Scale ◽  
Metals And Alloys ◽  
Analysis Tool ◽  
Computational Framework ◽  
Crystal Plasticity Finite Element ◽  
Polycrystalline Metals ◽  
Simulation Based ◽  
Open Source Framework

AbstractThe PRISMS-Fatigue open-source framework for simulation-based analysis of microstructural influences on fatigue resistance for polycrystalline metals and alloys is presented here. The framework uses the crystal plasticity finite element method as its microstructure analysis tool and provides a highly efficient, scalable, flexible, and easy-to-use ICME community platform. The PRISMS-Fatigue framework is linked to different open-source software to instantiate microstructures, compute the material response, and assess fatigue indicator parameters. The performance of PRISMS-Fatigue is benchmarked against a similar framework implemented using ABAQUS. Results indicate that the multilevel parallelism scheme of PRISMS-Fatigue is more efficient and scalable than ABAQUS for large-scale fatigue simulations. The performance and flexibility of this framework is demonstrated with various examples that assess the driving force for fatigue crack formation of microstructures with different crystallographic textures, grain morphologies, and grain numbers, and under different multiaxial strain states, strain magnitudes, and boundary conditions.

scholarly journals Health and longevity studies in C. elegans: the “healthy worm database” reveals strengths, weaknesses and gaps of test compound-based studies

2021 ◽  
Vol 22 (2) ◽  
pp. 215-236
Author(s):  
Nadine Saul ◽  
Steffen Möller ◽  
Francesca Cirulli ◽  
Alessandra Berry ◽  
Walter Luyten ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Model Organism ◽  
Research Field ◽  
Aging Research ◽  
Genetic Manipulations ◽  
C Elegans ◽  
Starting Point ◽  
Health Related ◽  
Phenotype Measurement ◽  
Or Gene

AbstractSeveral biogerontology databases exist that focus on genetic or gene expression data linked to health as well as survival, subsequent to compound treatments or genetic manipulations in animal models. However, none of these has yet collected experimental results of compound-related health changes. Since quality of life is often regarded as more valuable than length of life, we aim to fill this gap with the “Healthy Worm Database” (http://healthy-worm-database.eu). Literature describing health-related compound studies in the aging model Caenorhabditis elegans was screened, and data for 440 compounds collected. The database considers 189 publications describing 89 different phenotypes measured in 2995 different conditions. Besides enabling a targeted search for promising compounds for further investigations, this database also offers insights into the research field of studies on healthy aging based on a frequently used model organism. Some weaknesses of C. elegans-based aging studies, like underrepresented phenotypes, especially concerning cognitive functions, as well as the convenience-based use of young worms as the starting point for compound treatment or phenotype measurement are discussed. In conclusion, the database provides an anchor for the search for compounds affecting health, with a link to public databases, and it further highlights some potential shortcomings in current aging research.

scholarly journals Investigating the properties of a galaxy group at z = 0.6

2020 ◽  
Vol 15 (S359) ◽  
pp. 188-189
Author(s):  
Daniela Hiromi Okido ◽  
Cristina Furlanetto ◽  
Marina Trevisan ◽  
Mônica Tergolina
Keyword(s):  
Large Scale ◽  
The Other ◽  
Numerical Density ◽  
Spectroscopy Data ◽  
Stellar Kinematics ◽  
Galaxy Groups ◽  
The Galaxy ◽  
The Difference ◽  
The Impact ◽  
The Universe

AbstractGalaxy groups offer an important perspective on how the large-scale structure of the Universe has formed and evolved, being great laboratories to study the impact of the environment on the evolution of galaxies. We aim to investigate the properties of a galaxy group that is gravitationally lensing HELMS18, a submillimeter galaxy at z = 2.39. We obtained multi-object spectroscopy data using Gemini-GMOS to investigate the stellar kinematics of the central galaxies, determine its members and obtain the mass, radius and the numerical density profile of this group. Our final goal is to build a complete description of this galaxy group. In this work we present an analysis of its two central galaxies: one is an active galaxy with z = 0.59852 ± 0.00007, while the other is a passive galaxy with z = 0.6027 ± 0.0002. Furthermore, the difference between the redshifts obtained using emission and absorption lines indicates an outflow of gas with velocity v = 278.0 ± 34.3 km/s relative to the galaxy.

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