The WashU Epigenome Browser (https://epigenomegateway.wustl.edu/) provides visualization, integration and analysis tools for epigenomic datasets. Since 2010, it has provided the scientific community ...with data from large consortia including the Roadmap Epigenomics and the ENCODE projects. Recently, we refactored the codebase, redesigned the user interface, and developed various novel features. New features include: (i) visualization using virtual reality (VR), which has implications in biology education and the study of 3D chromatin structure; (ii) expanded public data hubs, including data from the 4DN, ENCODE, Roadmap Epigenomics, TaRGET, IHEC and TCGA consortia; (iii) a more responsive user interface; (iv) a history of interactions, which enables undo and redo; (v) a feature we call Live Browsing, which allows multiple users to collaborate remotely on the same session; (vi) the ability to visualize local tracks and data hubs. Amazon Web Services also hosts the redesign at https://epigenomegateway.org/.
Here, we introduce the 3D Genome Browser, http://3dgenome.org , which allows users to conveniently explore both their own and over 300 publicly available chromatin interaction data of different ...types. We design a new binary data format for Hi-C data that reduces the file size by at least a magnitude and allows users to visualize chromatin interactions over millions of base pairs within seconds. Our browser provides multiple methods linking distal cis-regulatory elements with their potential target genes. Users can seamlessly integrate thousands of other omics data to gain a comprehensive view of both regulatory landscape and 3D genome structure.
Transposable elements (TEs) have been shown to contain functional binding sites for certain transcription factors (TFs). However, the extent to which TEs contribute to the evolution of TF binding ...sites is not well known. We comprehensively mapped binding sites for 26 pairs of orthologous TFs in two pairs of human and mouse cell lines (representing two cell lineages), along with epigenomic profiles, including DNA methylation and six histone modifications. Overall, we found that 20% of binding sites were embedded within TEs. This number varied across different TFs, ranging from 2% to 40%. We further identified 710 TF-TE relationships in which genomic copies of a TE subfamily contributed a significant number of binding peaks for a TF, and we found that LTR elements dominated these relationships in human. Importantly, TE-derived binding peaks were strongly associated with open and active chromatin signatures, including reduced DNA methylation and increased enhancer-associated histone marks. On average, 66% of TE-derived binding events were cell type-specific with a cell type-specific epigenetic landscape. Most of the binding sites contributed by TEs were species-specific, but we also identified binding sites conserved between human and mouse, the functional relevance of which was supported by a signature of purifying selection on DNA sequences of these TEs. Interestingly, several TFs had significantly expanded binding site landscapes only in one species, which were linked to species-specific gene functions, suggesting that TEs are an important driving force for regulatory innovation. Taken together, our data suggest that TEs have significantly and continuously shaped gene regulatory networks during mammalian evolution.
Federated Learning (FL) is a privacy-preserving way to utilize the sensitive data generated by smart sensors of user devices, where a central parameter server (PS) coordinates multiple user devices ...to train a global model. However, relying on centralized topology poses challenges when applying FL in a sensors network, including imbalanced communication congestion and possible single point of failure, especially on the PS. To alleviate these problems, we devise a Dynamic Average Consensus-based Federated Learning (DACFL) for implementing FL in a decentralized sensors network. Different from existing studies that replace the model aggregation roughly with neighbors' average, we first transform the FL model aggregation, which is the most intractable in a decentralized topology, into the dynamic average consensus problem by treating a local training procedure as a discrete-time series.We then employ the first-order dynamic average consensus (FODAC) to estimate the average model, which not only solves the model aggregation for DACFL but also ensures model consistency as much as possible. To improve the performance with non-i.i.d data, each user also takes the neighbors' average model as its next-round initialization, which prevents the possible local over-fitting. Besides, we also provide a basic theoretical analysis of DACFL on the premise of i.i.d data. The result validates the feasibility of DACFL in both time-invariant and time-varying topologies and declares that DACFL outperforms existing studies, including CDSGD and D-PSGD, in most cases. Take the result on Fashion-MNIST as a numerical example, with i.i.d data, our DACFL achieves 19∼34% and 3∼10% increases in average accuracy; with non-i.i.d data, our DACFL achieves 30∼50% and 0∼10% increases in average accuracy, compared to CDSGD and D-PSGD.
Abstract
WashU Epigenome Browser (https://epigenomegateway.wustl.edu/browser/) is a web-based genomic data exploration tool that provides visualization, integration, and analysis of epigenomic ...datasets. The newly renovated user interface and functions have enabled researchers to engage with the browser and genomic data more efficiently and effectively since 2018. Here, we introduce a new integrated panel design in the browser that allows users to interact with 1D (genomic features), 2D (such as Hi-C), 3D (genome structure), and 4D (time series) data in a single web page. The browser can display three-dimensional chromatin structures with the 3D viewer module. The 4D tracks, called ‘Dynamic’ tracks, animatedly display time-series data, allowing for a more striking visual impact to identify the gene or genomic region candidates as a function of time. Genomic data, such as annotation features, numerical values, and chromatin interaction data can all be viewed in the dynamic track mode. Imaging data from microscopy experiments can also be displayed in the browser. In addition to software development, we continue to service and expand the data hubs we host for large consortia including 4DN, Roadmap Epigenomics, TaRGET and ENCODE, among others. Our growing user/developer community developed additional track types as plugins, such as qBed and dynseq tracks, which extend the utility of the browser. The browser serves as a foundation for additional genomics platforms including the WashU Virus Genome Browser (for COVID-19 research) and the Comparative Genome Browser. The WashU Epigenome Browser can also be accessed freely through Amazon Web Services at https://epigenomegateway.org/.
Graphical Abstract
Graphical Abstract
New components of WashU Epigenome Browser: 3D chromatin viewer, imaging data viewer and dynamic tracks.
The explosive growth of malware targeting Android devices has resulted in the demand for the acquisition and integration of comprehensive information to enable effective, robust, and user-friendly ...malware detection. In response to this challenge, this paper introduces HertDroid, an innovative Android malware detection method that leverages the hidden contextual information within application entities. Specifically, we formulate a heterogeneous graph encapsulating rich semantics of entities and their interactions to model the behavior of Android applications. To alleviate computational burdens, a filter is implemented to identify nodes containing crucial information. The Transformer architecture is then deployed for efficient information aggregation across diverse entities. In our experiments, HertDroid demonstrates superior performance by achieving the highest F1 scores when compared to baseline methods on a dataset comprising 10,361 benign and 11,043 malicious apps. Notably, HertDroid excels in maintaining a lightweight profile, and its performance is achieved without the necessity of manual meta-path configuration.
Several mechanisms of action have been proposed for DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi), primarily based on candidate-gene approaches. However, less is known ...about their genome-wide transcriptional and epigenomic consequences. By mapping global transcription start site (TSS) and chromatin dynamics, we observed the cryptic transcription of thousands of treatment-induced non-annotated TSSs (TINATs) following DNMTi and HDACi treatment. The resulting transcripts frequently splice into protein-coding exons and encode truncated or chimeric ORFs translated into products with predicted abnormal or immunogenic functions. TINAT transcription after DNMTi treatment coincided with DNA hypomethylation and gain of classical promoter histone marks, while HDACi specifically induced a subset of TINATs in association with H2AK9ac, H3K14ac, and H3K23ac. Despite this mechanistic difference, both inhibitors convergently induced transcription from identical sites, as we found TINATs to be encoded in solitary long terminal repeats of the ERV9/LTR12 family, which are epigenetically repressed in virtually all normal cells.
We investigated maternal obesity in inbred SM/J mice by assigning females to a high-fat diet or a low-fat diet at weaning, mating them to low-fat-fed males, cross-fostering the offspring to ...low-fat-fed SM/J nurses at birth, and weaning the offspring onto a high-fat or low-fat diet. A maternal high-fat diet exacerbated obesity in the high-fat-fed daughters, causing them to weigh more, have more fat, and have higher serum levels of leptin as adults, accompanied by dozens of gene expression changes and thousands of DNA methylation changes in their livers and hearts. Maternal diet particularly affected genes involved in RNA processing, immune response, and mitochondria. Between one-quarter and one-third of differentially expressed genes contained a differentially methylated region associated with maternal diet. An offspring high-fat diet reduced overall variation in DNA methylation, increased body weight and organ weights, increased long bone lengths and weights, decreased insulin sensitivity, and changed the expression of 3,908 genes in the liver. Although the offspring were more affected by their own diet, their maternal diet had epigenetic effects lasting through adulthood, and in the daughters these effects were accompanied by phenotypic changes relevant to obesity and diabetes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The zebrafish (Danio rerio) has been widely used in the study of human disease and development, and about 70% of the protein-coding genes are conserved between the two species
. However, studies in ...zebrafish remain constrained by the sparse annotation of functional control elements in the zebrafish genome. Here we performed RNA sequencing, assay for transposase-accessible chromatin using sequencing (ATAC-seq), chromatin immunoprecipitation with sequencing, whole-genome bisulfite sequencing, and chromosome conformation capture (Hi-C) experiments in up to eleven adult and two embryonic tissues to generate a comprehensive map of transcriptomes, cis-regulatory elements, heterochromatin, methylomes and 3D genome organization in the zebrafish Tübingen reference strain. A comparison of zebrafish, human and mouse regulatory elements enabled the identification of both evolutionarily conserved and species-specific regulatory sequences and networks. We observed enrichment of evolutionary breakpoints at topologically associating domain boundaries, which were correlated with strong histone H3 lysine 4 trimethylation (H3K4me3) and CCCTC-binding factor (CTCF) signals. We performed single-cell ATAC-seq in zebrafish brain, which delineated 25 different clusters of cell types. By combining long-read DNA sequencing and Hi-C, we assembled the sex-determining chromosome 4 de novo. Overall, our work provides an additional epigenomic anchor for the functional annotation of vertebrate genomes and the study of evolutionarily conserved elements of 3D genome organization.
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