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Collectively, these findings suggest that the results of the present study may be underestimating species richness among mites and their host mussels. Unfortunately, human perturbations are known to have caused high recent rates of extinction in the mussel and mite faunas of North America and could play a major role in influencing patterns of species richness for this host-parasite system moving forward.Impairment of intestinal barrier function is linked to certain pathologies and to aging, and can be a cause of bacterial infections, systemic and hepatic inflammation, food allergies, and autoimmune disorders. The formation and maintenance of intestinal tight junctions is supported by glucagon-like peptide-2 (GLP-2), which via insulin-like growth factor I activity boosts phosphoinositide 3-kinase/Akt/mammalian target of rapamycin complex 1 (PI3K/Akt/mTORC1) signaling in enterocytes. 5'-AMP-activated protein kinase (AMPK) activity as well as estrogen receptor-β (ERβ) activity are also protective in this regard. Conversely, activation of mitogen-activated protein kinases (MAPKs) and cellular Src (c-Src) under inflammatory conditions can induce dissociation of tight junctions. Hence, nutraceuticals that promote GLP-2 secretion from L cells-effective pre/probiotics, glycine, and glutamine-as well as diets rich in soluble fiber or resistant starch, can support intestinal barrier function. AMPK activators-notably berberine and the butyric acid produced by health-promoting microflora-are also beneficial in this regard, as are soy isoflavones, which function as selective agonists for ERβ. The adverse impact of MAPK and c-Src overactivation on the intestinal barrier can be combatted with various antioxidant measures, including phycocyanobilin, phase 2-inducer nutraceuticals, and N-acetylcysteine. These considerations suggest that rationally designed functional foods or complex supplementation programs could have clinical potential for supporting and restoring healthful intestinal barrier function.Cells are compartmentalized by numerous membrane-bounded organelles and membraneless organelles (MLOs) to ensure temporal and spatial regulation of various biological processes. A number of MLOs, such as nucleoli, nuclear speckles and stress granules, exist as liquid droplets within the cells and arise from the condensation of proteins and RNAs via liquid-liquid phase separation (LLPS). By concentrating certain proteins and RNAs, MLOs accelerate biochemical reactions and protect cells during stress, and dysfunction of MLOs is associated with various pathological processes. With the development in this field, more and more relations between the MLOs and diseases have been described; however, these results have not been made available in a centralized resource. Herein, we build MloDisDB, a database which aims to gather the relations between MLOs and diseases from dispersed literature. #link# In addition, the relations between LLPS and diseases were included as well. Currently, MloDisDB contains 771 curated entries from 607 publications; each entry in MloDisDB contains detailed information about the MLO, the disease and the functional factor in the relation. Furthermore, an efficient and user-friendly interface for users to search, browse and download all entries was provided. MloDisDB is the first comprehensive database of the relations between MLOs and diseases so far, and the database is freely accessible at http//mlodis.phasep.pro/.Breast cancer is a highly heterogeneous disease, and there are many forms of categorization for breast cancer based on gene expression profiles. Gene expression profiles are variables and may show differences if measured at different time points or under different conditions. In contrast, biological networks are relatively stable over time and under different conditions. In this study, we used a gene interaction network from a new point of view to explore the subtypes of breast cancer based on individual-specific edge perturbations measured by relative gene expression value. Our study reveals that there are four breast cancer subtypes based on gene interaction perturbations at the individual level. The new network-based subtypes of breast cancer show strong heterogeneity in prognosis, somatic mutations, phenotypic changes and enriched pathways. The network-based subtypes are closely related to the PAM50 subtypes and immunohistochemistry index. This work helps us to better understand the heterogeneity and mechanisms of breast cancer from a network perspective.The triangular correlation heatmap aiming to visualize the linkage disequilibrium (LD) pattern and haplotype block structure of SNPs is ubiquitous component of population-based genetic studies. However, current tools suffered from the problem of time and memory consuming. Here, we developed LDBlockShow, an open source software, for visualizing LD and haplotype blocks from variant call format files. It is time and memory saving. In a test dataset with 100 SNPs from 60 000 subjects, it was at least 10.60 times faster and used only 0.03-13.33% of physical memory as compared with other tools. In addition, it could generate figures that simultaneously display additional statistical context (e.g. association P-values) and genomic region annotations. It can also compress the SVG files with a large number of SNPs and support subgroup analysis. This fast and convenient tool will facilitate the visualization of LD and haplotype blocks for geneticists.An interaction between pharmacological agents can trigger unexpected adverse events. Capturing richer and more comprehensive information about drug-drug interactions (DDIs) is one of the key tasks in public health and drug development. Recently, several knowledge graph (KG) embedding approaches have received increasing attention in the DDI domain due to their capability of projecting drugs and interactions into a low-dimensional feature space for predicting links and classifying triplets. However, existing methods only apply a uniformly random mode to construct negative samples. As a consequence, these samples are often too simplistic to train an effective model. In this paper, we propose a new KG embedding framework by introducing adversarial autoencoders (AAEs) based on Wasserstein distances and Gumbel-Softmax relaxation for DDI tasks. In check details , the autoencoder is employed to generate high-quality negative samples and the hidden vector of the autoencoder is regarded as a plausible drug candidate. Afterwards, the discriminator learns the embeddings of drugs and interactions based on both positive and negative triplets. Meanwhile, in order to solve vanishing gradient problems on the discrete representation-an inherent flaw in traditional generative models-we utilize the Gumbel-Softmax relaxation and the Wasserstein distance to train the embedding model steadily. We empirically evaluate our method on two tasks link prediction and DDI classification. The experimental results show that our framework can attain significant improvements and noticeably outperform competitive baselines. Supplementary information Supplementary data and code are available at https//github.com/dyf0631/AAE_FOR_KG.The identification of hidden responders is often an essential challenge in precision oncology. A recent attempt based on machine learning has been proposed for classifying aberrant pathway activity from multiomic cancer data. link2 However, we note several critical limitations there, such as high-dimensionality, data sparsity and model performance. Given the central importance and broad impact of precision oncology, we propose nature-inspired deep Ras activation pan-cancer (NatDRAP), a deep neural network (DNN) model, to address those restrictions for the identification of hidden responders. In this study, we develop the nature-inspired deep learning model that integrates bulk RNA sequencing, copy number and mutation data from PanCanAltas to detect pan-cancer Ras pathway activation. In NatDRAP, we propose to synergize the nature-inspired artificial bee colony algorithm with different gradient-based optimizers in one framework for optimizing DNNs in a collaborative manner. Multiple experiments were conducted on 33 different cancer types across PanCanAtlas. The experimental results demonstrate that the proposed NatDRAP can provide superior performance over other benchmark methods with strong robustness towards diagnosing RAS aberrant pathway activity across different cancer types. In addition, gene ontology enrichment and pathological analysis are conducted to reveal novel insights into the RAS aberrant pathway activity identification and characterization. NatDRAP is written in Python and available at https//github.com/lixt314/NatDRAP1.Accessory proteins play important roles in the interaction between coronaviruses and their hosts. Accordingly, a comprehensive study of the compositional diversity and evolutionary patterns of accessory proteins is critical to understanding the host adaptation and epidemic variation of coronaviruses. Here, we developed a standardized genome annotation tool for coronavirus (CoroAnnoter) by combining open reading frame prediction, transcription regulatory sequence recognition and homologous alignment. Using CoroAnnoter, we annotated 39 representative coronavirus strains to form a compositional profile for all of the accessary proteins. Large variations were observed in the number of accessory proteins of 1-10 for different coronaviruses, with SARS-CoV-2 and SARS-CoV having the most (9 and 10, respectively). link3 The variation between SARS-CoV and SARS-CoV-2 accessory proteins could be traced back to related coronaviruses in other hosts. The genomic distribution of accessory proteins had significant intra-genus conservation and inter-genus diversity and could be grouped into 1, 4, 2 and 1 types for alpha-, beta-, gamma-, and delta-coronaviruses, respectively. Evolutionary analysis suggested that accessory proteins are more conservative locating before the N-terminal of proteins E and M (E-M), while they are more diverse after these proteins. Furthermore, comparison of virus-host interaction networks of SARS-CoV-2 and SARS-CoV accessory proteins showed that they share multiple antiviral signaling pathways, those involved in the apoptotic process, viral life cycle and response to oxidative stress. In summary, our study provides a tool for coronavirus genome annotation and builds a comprehensive profile for coronavirus accessory proteins covering their composition, classification, evolutionary pattern and host interaction.Over the last decade, genome-wide association studies (GWAS) have discovered thousands of genetic variants underlying complex human diseases and agriculturally important traits. These findings have been utilized to dissect the biological basis of diseases, to develop new drugs, to advance precision medicine and to boost breeding. However, the potential of GWAS is still underexploited due to methodological limitations. Many challenges have emerged, including detecting epistasis and single-nucleotide polymorphisms (SNPs) with small effects and distinguishing causal variants from other SNPs associated through linkage disequilibrium. These issues have motivated advancements in GWAS analyses in two contrasting cultures-statistical modelling and machine learning. In this review, we systematically present the basic concepts and the benefits and limitations in both methods. We further discuss recent efforts to mitigate their weaknesses. Additionally, we summarize the state-of-the-art tools for detecting the missed signals, ultrarare mutations and gene-gene interactions and for prioritizing SNPs.
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