134 research outputs found

    Assessment Method for a Power Analysis to Identify Differentially Expressed Pathways

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    Gene expression data can provide a very rich source of information for elucidating the biological function on the pathway level if the experimental design considers the needs of the statistical analysis methods. The purpose of this paper is to provide a comparative analysis of statistical methods for detecting the differentially expression of pathways (DEP). In contrast to many other studies conducted so far, we use three novel simulation types, producing a more realistic correlation structure than previous simulation methods. This includes also the generation of surrogate data from two large-scale microarray experiments from prostate cancer and ALL. As a result from our comprehensive analysis of [Image: see text] parameter configurations, we find that each method should only be applied if certain conditions of the data from a pathway are met. Further, we provide method-specific estimates for the optimal sample size for microarray experiments aiming to identify DEP in order to avoid an underpowered design. Our study highlights the sensitivity of the studied methods on the parameters of the system

    Constrained Covariance Matrices With a Biologically Realistic Structure: Comparison of Methods for Generating High-Dimensional Gaussian Graphical Models

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    High-dimensional data from molecular biology possess an intricate correlation structure that is imposed by the molecular interactions between genes and their products forming various different types of gene networks. This fact is particularly well-known for gene expression data, because there is a sufficient number of large-scale data sets available that are amenable for a sensible statistical analysis confirming this assertion. The purpose of this paper is two fold. First, we investigate three methods for generating constrained covariance matrices with a biologically realistic structure. Such covariance matrices are playing a pivotal role in designing novel statistical methods for high-dimensional biological data, because they allow to define Gaussian graphical models (GGM) for the simulation of realistic data; including their correlation structure. We study local and global characteristics of these covariance matrices, and derived concentration/partial correlation matrices. Second, we connect these results, obtained from a probabilistic perspective, to statistical results of studies aiming to estimate gene regulatory networks from biological data. This connection allows to shed light on the well-known heterogeneity of statistical estimation methods for inferring gene regulatory networks and provides an explanation for the difficulties inferring molecular interactions between highly connected genes

    Unleashing the power of Virtual Reality to manage LAZY EYE-A silent public health problem: A case study from India

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    Amblyopia, also known as "lazy eye," is a childhood vision disorder characterized by impaired coordination between the brain and the eye, resulting in decreased vision in one eye. It is not caused by any structural abnormalities in the eye but rather by a lack of effective coordination between the eye and brain during the crucial period of visual development in early childhood.(1) Amblyopia is a significant global public health issue, with an estimated prevalence of 1-5% of the global population according to the World Health Organization (WHO). Developing countries face a higher burden of amblyopia due to limited access to early diagnosis and treatment. If left untreated, amblyopia can result in permanent vision loss and impairment, negatively impacting an individual's quality of life, educational achievements, and career prospects.(1) A 2017 study explored the prevalence and impact of amblyopia and strabismus in Indian children. The study found a prevalence rate of 1.67% for amblyopia among children aged 5-15 years, with a higher occurrence in rural areas compared to urban areas.(2)  In another study conducted by Gupta et al. found the percentage of amblyopia was 8.6% (n=31) among 5-15 years children in uttrakhand.(3) Another study conducted by Ganekal et al. revealed the prevalence of amblyopia was 1.1% (n?=?44) among 5-15 years of students.(4) The research emphasized the importance of enhanced awareness, early detection, and improved access to suitable treatment options to alleviate the burden of amblyopia in India. Furthermore, the All India Ophthalmological Society (AIOS) conducted a study in 2019 titled "AIOS Guidelines for Amblyopia Management." This study aimed to provide evidence-based guidelines for managing amblyopia in India. It highlighted the lack of awareness and limited availability of eye care services in certain regions, leading to delayed diagnosis and treatment of amblyopia. The guidelines emphasized the significance of early screening, timely intervention, and appropriate treatment approaches to prevent long-term visual impairment in children.(5

    Graph-based exploitation of gene ontology using GOxploreR for scrutinizing biological significance.

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    Gene ontology (GO) is an eminent knowledge base frequently used for providing biological interpretations for the analysis of genes or gene sets from biological, medical and clinical problems. Unfortunately, the interpretation of such results is challenging due to the large number of GO terms, their hierarchical and connected organization as directed acyclic graphs (DAGs) and the lack of tools allowing to exploit this structural information explicitly. For this reason, we developed the R package GOxploreR. The main features of GOxploreR are (I) easy and direct access to structural features of GO, (II) structure-based ranking of GO-terms, (III) mapping to reduced GO-DAGs including visualization capabilities and (IV) prioritizing of GO-terms. The underlying idea of GOxploreR is to exploit a graph-theoretical perspective of GO as manifested by its DAG-structure and the containing hierarchy levels for cumulating semantic information. That means all these features enhance the utilization of structural information of GO and complement existing analysis tools. Overall, GOxploreR provides exploratory as well as confirmatory tools for complementing any kind of analysis resulting in a list of GO-terms, e.g., from differentially expressed genes or gene sets, GWAS or biomarkers. Our R package GOxploreR is freely available from CRAN

    The MILLET MISSION: The potential to combat non-communicable diseases and future research opportunities in India

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    NCD Burden and the role of nutritionChronic diseases, often known as non-communicable diseases (NCDs), pose a significant threat to worldwide public health. As per World Health Organisation (WHO), NCDs account for 74% of all fatalities worldwide, with cardiovascular disease, cancer, respiratory disease, and diabetes being the leading causes.[1] Inadequate nutrition, including diets heavy in sugar, salt, saturated and trans fats, and deficient in fruits, vegetables, whole grains, and lean protein sources, is a significant risk factor for NCDs. The World Health Organization suggests a diet rich in fruits, vegetables, whole grains, nuts, and seeds and low in processed foods, sugar, saturated and trans fats.[2

    Analyzing the Scholarly Literature of Digital Twin Research : Trends, Topics and Structure

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    Currently, studies involving a digital twin are gaining widespread interest. While the first fields adopting such a concept were in manufacturing and engineering, lately, interest extends also beyond these fields across all academic disciplines. Given the inviting idea behind a digital twin which allows the efficient exploitation and utilization of simulations such a trend is understandable. The purpose of this paper is to use a scientometrics approach to study the early publication history of the digital twin across academia. Our analysis is based on large-scale bibliographic and citation data from Scopus that provides authoritative information about high-quality publications in essentially all fields of science, engineering and humanities. This paper has four major objectives. First, we obtain a global overview of all publications related to a digital twin across all major subject areas. This analysis provides insights into the structure of the entire publication corpus. Second, we investigate the co-occurrence of subject areas appearing together on publications. This reveals interdisciplinary relations of the publications and identifies the most collaborative fields. Third, we conduct a trend and keyword analysis to gain insights into the evolution of the concept and the importance of keywords. Fourth, based on results from topic modeling using a Latent Dirichlet Allocation (LDA) model we introduce the definition of a scientometric dimension (SD) of digital twin research that allows to summarize an important aspect of the bound diversity of the academic literature.Peer reviewe

    An intercalation-locked parallel-stranded DNA tetraplex

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    Funding for Open Access provided by the UMD Libraries Open Access Publishing Fund.DNA has proved to be an excellent material for nanoscale construction because complementary DNA duplexes are programmable and structurally predictable. However, in the absence of Watson– Crick pairings, DNA can be structurally more diverse. Here, we describe the crystal structures of d(ACTCGGATGAT) and the brominated derivative, d(ACBrUCGGABrUGAT). These oligonucleotides form parallel-stranded duplexes with a crystallographically equivalent strand, resulting in the first examples of DNA crystal structures that contains four different symmetric homo base pairs. Two of the parallel-stranded duplexes are coaxially stacked in opposite directions and locked together to form a tetraplex through intercalation of the 5’-most A–A base pairs between adjacent G–G pairs in the partner duplex. The intercalation region is a new type of DNA tertiary structural motif with similarities to the i-motif. 1H–1H nuclear magnetic resonance and native gel electrophoresis confirmed the formation of a parallel-stranded duplex in solution. Finally, we modified specific nucleotide positions and added d(GAY) motifs to oligonucleotides and were readily able to obtain similar crystals. This suggests that this parallel-stranded DNA structure may be useful in the rational design of DNA crystals and nanostructures
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