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  1. Abstract

    We proposed a novel interaction potential landscape approach to map the systems-level profile changes of gene networks during replicative aging inSaccharomyces cerevisiae. This approach enabled us to apply quasi-potentials, the negative logarithm of the probabilities, to calibrate the elevation of the interaction landscapes with young cells as a reference state. Our approach detected opposite landscape changes based on protein abundances from transcript levels, especially for intra-essential gene interactions. We showed that essential proteins play different roles from hub proteins on the age-dependent interaction potential landscapes. We verified that hub proteins tend to avoid other hub proteins, but essential proteins prefer to interact with other essential proteins. Overall, we showed that the interaction potential landscape is promising for inferring network profile change during aging and that the essential hub proteins may play an important role in the uncoupling between protein and transcript levels during replicative aging.

     
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  2. Premise

    The digitization of natural history collections includes transcribing specimen label data into standardized formats. Born‐digital specimen data initially gathered in digital formats do not need to be transcribed, enabling their efficient integration into digitized collections. Modernizing field collection methods for born‐digital workflows requires the development of new tools and processes.

    Methods and Results

    collNotes, a mobile application, was developed for Android andiOSto supplement traditional field journals. Designed for efficiency in the field, collNotes avoids redundant data entries and does not require cellular service. collBook, a companion desktop application, refines field notes into database‐ready formats and produces specimen labels.

    Conclusions

    collNotes and collBook can be used in combination as a field‐to‐database solution for gathering born‐digital voucher specimen data for plants and fungi. Both programs are open source and use common file types simplifying either program's integration into existing workflows.

     
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  3. Abstract

    The non-random interaction pattern of a protein–protein interaction network (PIN) is biologically informative, but its potentials have not been fully utilized in omics studies. Here, we propose a network-permutation-based association study (NetPAS) method that gauges the observed interactions between two sets of genes based on the comparison between permutation null models and the empirical networks. This enables NetPAS to evaluate relationships, constrained by network topology, between gene sets related to different phenotypes. We demonstrated the utility of NetPAS in 50 well-curated gene sets and comparison of association studies using Z-scores, modified Zʹ-scores, p-values and Jaccard indices. Using NetPAS, a weighted human disease network was generated from the association scores of 19 gene sets from OMIM. We also applied NetPAS in gene sets derived from gene ontology and pathway annotations and showed that NetPAS uncovered functional terms missed by DAVID and WebGestalt. Overall, we show that NetPAS can take topological constraints of molecular networks into account and offer new perspectives than existing methods.

     
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  4. The global rise in heart disease necessitates precise prediction tools to assess individual risk levels. This paper introduces a novel Multi-Objective Artificial Bee Colony Optimized Hybrid Deep Belief Network and XGBoost (HDBN-XG) algorithm, enhancing coronary heart disease prediction accuracy. Key physiological data, including Electrocardiogram (ECG) readings and blood volume measurements, are analyzed. The HDBN-XG algorithm assesses data quality, normalizes using z-score values, extracts features via the Computational Rough Set method, and constructs feature subsets using the Multi-Objective Artificial Bee Colony approach. Our findings indicate that the HDBN-XG algorithm achieves an accuracy of 99%, precision of 95%, specificity of 98%, sensitivity of 97%, and F1-measure of 96%, outperforming existing classifiers. This paper contributes to predictive analytics by offering a data-driven approach to healthcare, providing insights to mitigate the global impact of coronary heart disease.

     
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    Free, publicly-accessible full text available November 16, 2024
  5. Introduction: Essential genes are essential for the survival of various species. These genes are a family linked to critical cellular activities for species survival. These genes are coded for proteins that regulate central metabolism, gene translation, deoxyribonucleic acid replication, and fundamental cellular structure and facilitate intracellular and extracellular transport. Essential genes preserve crucial genomics information that may hold the key to a detailed knowledge of life and evolution. Essential gene studies have long been regarded as a vital topic in computational biology due to their relevance. An essential gene is composed of adenine, guanine, cytosine, and thymine and its various combinations. Methods: This paper presents a novel method of extracting information on the stationary patterns of nucleotides such as adenine, guanine, cytosine, and thymine in each gene. For this purpose, some co-occurrence matrices are derived that provide the statistical distribution of stationary patterns of nucleotides in the genes, which is helpful in establishing the relationship between the nucleotides. For extracting discriminant features from each co-occurrence matrix, energy, entropy, homogeneity, contrast, and dissimilarity features are computed, which are extracted from all co-occurrence matrices and then concatenated to form a feature vector representing each essential gene. Finally, supervised machine learning algorithms are applied for essential gene classification based on the extracted fixed-dimensional feature vectors. Results: For comparison, some existing state-of-the-art feature representation techniques such as Shannon entropy (SE), Hurst exponent (HE), fractal dimension (FD), and their combinations have been utilized. Discussion: An extensive experiment has been performed for classifying the essential genes of five species that show the robustness and effectiveness of the proposed methodology. 
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    Free, publicly-accessible full text available April 20, 2024
  6. Bonomo, Robert A. (Ed.)
    ABSTRACT Microbial diversity is reduced in the gut microbiota of animals and humans treated with selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs). The mechanisms driving the changes in microbial composition, while largely unknown, is critical to understand considering that the gut microbiota plays important roles in drug metabolism and brain function. Using Escherichia coli , we show that the SSRI fluoxetine and the TCA amitriptyline exert strong selection pressure for enhanced efflux activity of the AcrAB-TolC pump, a member of the resistance-nodulation-cell division (RND) superfamily of transporters. Sequencing spontaneous fluoxetine- and amitriptyline-resistant mutants revealed mutations in marR and lon, negative regulators of AcrAB-TolC expression. In line with the broad specificity of AcrAB-TolC pumps these mutants conferred resistance to several classes of antibiotics. We show that the converse also occurs, as spontaneous chloramphenicol-resistant mutants displayed cross-resistance to SSRIs and TCAs. Chemical-genomic screens identified deletions in marR and lon, confirming the results observed for the spontaneous resistant mutants. In addition, deletions in 35 genes with no known role in drug resistance were identified that conferred cross-resistance to antibiotics and several displayed enhanced efflux activities. These results indicate that combinations of specific antidepressants and antibiotics may have important effects when both are used simultaneously or successively as they can impose selection for common mechanisms of resistance. Our work suggests that selection for enhanced efflux activities is an important factor to consider in understanding the microbial diversity changes associated with antidepressant treatments. IMPORTANCE Antidepressants are prescribed broadly for psychiatric conditions to alter neuronal levels of synaptic neurotransmitters such as serotonin and norepinephrine. Two categories of antidepressants are selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs); both are among the most prescribed drugs in the United States. While it is well-established that antidepressants inhibit reuptake of neurotransmitters there is evidence that they also impact microbial diversity in the gastrointestinal tract. However, the mechanisms and therefore biological and clinical effects remain obscure. We demonstrate antidepressants may influence microbial diversity through strong selection for mutant bacteria with increased AcrAB-TolC activity, an efflux pump that removes antibiotics from cells. Furthermore, we identify a new group of genes that contribute to cross-resistance between antidepressants and antibiotics, several act by regulating efflux activity, underscoring overlapping mechanisms. Overall, this work provides new insights into bacterial responses to antidepressants important for understanding antidepressant treatment effects. 
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  7. High-throughput microfluidics-based assays can potentially increase the speed and quality of yeast replicative lifespan measurements. One major challenge is to efficiently convert large volumes of time-lapse images into quantitative measurements of cellular lifespans. Here, we address this challenge by prototyping an algorithm that can track cellular division events through family trees of cells. We generated a null distribution using single cells inside microfluidic traps. Based on this null distribution, we prototyped a maximum likelihood algorithm for cell tracking between images at different time-points. We inferred cell family trees through a likelihood based trace-back method. The branching patterns of the cell family trees are then used to infer replicative lifespan of the yeast mother cells. The longest branch of a cell family tree represents the full trajectory of a yeast mother cell. The replicative lifespan of this mother cell can be counted as the number of bifurcating branches of this family tree. In addition, we prototyped a different approach based on summing cells area which improved the replicative lifespan estimation significantly. These generic methods have the potential to accelerate the efficiency and expand the range of quantitative measurement of yeast replicative aging experiments. 
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