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  • Articles  (208,231)
  • Oxford University Press  (208,231)
  • Biology  (208,231)
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  • 1
    Publication Date: 2021-10-30
    Description: Motivation Coiled-coil is composed of two or more helices that are wound around each other. It widely exists in proteins and has been discovered to play a variety of critical roles in biology processes. Generally, there are three types of structural features in coiled-coil: coiled-coil domain (CCD), oligomeric state, and register. However, most of the existing computational tools only focus on one of them. Results Here, we describe a new deep learning model, CoCoPRED, which is based on convolutional layers, bidirectional long short-term memory, and attention mechanism. It has three networks, i.e., CCD network, oligomeric state network, and register network, corresponding to the three types of structural features in coiled-coil. This means CoCoPRED has the ability of fulfilling comprehensive prediction for coiled-coil proteins. Through the 5-fold cross-validation experiment, we demonstrate that CoCoPRED can achieve better performance than the state-of-the-art models on both CCD prediction and oligomeric state prediction. Further analysis suggests the CCD prediction may be a performance indicator of the oligomeric state prediction in CoCoPRED. The attention heads in CoCoPRED indicate that registers a, b, and e are more crucial for the oligomeric state prediction. Availability CoCoPRED is available at http://www.csbio.sjtu.edu.cn/bioinf/CoCoPRED. Supplementary information Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 2
    Publication Date: 2021-10-30
    Description: Epigenome-Wide Association Study (EWAS) has become a standard strategy to discover DNA methylation variation of different phenotypes. Since 2018, we have developed EWAS Atlas and EWAS Data Hub to integrate a growing volume of EWAS knowledge and data, respectively. Here, we present EWAS Open Platform (https://ngdc.cncb.ac.cn/ewas) that includes EWAS Atlas, EWAS Data Hub and the newly developed EWAS Toolkit. In the current implementation, EWAS Open Platform integrates 617 018 high-quality EWAS associations from 910 publications, covering 51 phenotypes, 275 diseases and 104 environmental factors. It also provides well-normalized DNA methylation array data and the corresponding metadata from 115 852 samples, which involve 707 tissues, 218 cell lines and 528 diseases. Taking advantage of integrated knowledge and data in EWAS Atlas and EWAS Data Hub, EWAS Open Platform equips with EWAS Toolkit, a powerful one-stop site for EWAS enrichment, annotation, and knowledge network construction and visualization. Collectively, EWAS Open Platform provides open access to EWAS knowledge, data and toolkit and thus bears great utility for a broader range of relevant research.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 3
    Publication Date: 2021-10-30
    Description: Motivation Alignment-free (AF) distance/similarity functions are a key tool for sequence analysis. Experimental studies on real datasets abound and, to some extent, there are also studies regarding their control of false positive rate (Type I error). However, assessment of their power, i.e., their ability to identify true similarity, has been limited to some members of the D2 family. The corresponding experimental studies have concentrated on short sequences, a scenario no longer adequate for current applications, where sequence lengths may vary considerably. Such a State of the Art is methodologically problematic, since information regarding a key feature such as power is either missing or limited. Results By concentrating on a representative set of word-frequency based AF functions, we perform the first coherent and uniform evaluation of the power, involving also Type I error for completeness. Two Alternative models of important genomic features (CIS Regulatory Modules and Horizontal Gene Transfer), a wide range of sequence lengths from a few thousand to millions, and different values of k have been used. As a result, we provide a characterization of those AF functions that is novel and informative. Indeed, we identify weak and strong points of each function considered, which may be used as a guide to choose one for analysis tasks. Remarkably, of the fifteen functions that we have considered, only four stand out, with small differences between small and short sequence length scenarios. Finally, in order to encourage the use of our methodology for validation of future AF functions, the Big Data platform supporting it is public. Availability The software is available at: https://github.com/pipp8/power_statistics Supplementary information Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 4
    Publication Date: 2021-10-30
    Description: Motivation Adverse Outcome Pathways (AOPs) are a conceptual framework developed to support the use of alternative toxicology approaches in the risk assessment. AOPs are structured linear organizations of existing knowledge illustrating causal pathways from the initial molecular perturbation triggered by various stressors, through key events (KEs) at different levels of biology, to the ultimate health or ecotoxicological adverse outcome. Results Artificial intelligence can be used to systematically explore available toxicological data that can be parsed in the scientific literature. Recently a tool called AOP-helpFinder was developed to identify associations between stressors and KEs supporting thus documentation of AOPs. To facilitate the utilization of this advanced bioinformatics tool by the scientific and the regulatory community, a webserver was created. The proposed AOP-helpFinder webserver uses better performing version of the tool which reduces the need for manual curation of the obtained results. As an example, the server was successfully applied to explore relationships of a set of endocrine disruptors with metabolic-related events. The AOP-helpFinder webserver assists in a rapid evaluation of existing knowledge stored in the PubMed database, a global resource of scientific information, to build AOPs and Adverse Outcome Networks (AONs) supporting the chemical risk assessment. Availability and implementation AOP-helpFinder is available at http://aop-helpfinder.u-paris-sciences.fr/index.php
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 5
    Publication Date: 2021-10-30
    Description: Assessment of zooplankton abundance, distribution, community composition, and temporal variability is critical to understanding the effects of climate variability and change on lower trophic level production and availability for consumption by larger consumers. Zooplankton sampling is performed across the Canadian continental shelf system by Fisheries and Oceans Canada's Atlantic Zone Monitoring Programme (AZMP). Sampling includes semi-monthly to monthly collection of zooplankton using vertical net tows (VNTs) deployed from near-bottom to surface at stations on the central Scotian Shelf (Stn 2, 150 m depth) and Newfoundland Shelf (Stn 27, 175 m depth), and by Continuous Plankton Recorders (CPRs) in the near-surface layers along routes over the Scotian and Newfoundland shelves (0–10 m depth). Here, we compare abundance metrics for 11 copepod taxa collected using both gear types in both regions between 1999 and 2015. Seasonal cycles of VNT and CPR abundance were similar for near-surface residents. VNT: CPR abundance ratios varied year-round for vertical migrants, as ontogenetic migrants shifted their vertical distribution, and as diel migrants changed their migratory behaviour. For some taxa, differences in annual average VNT: CPR abundance ratios between regions suggest differences in vertical distribution, while for others differences in inter-annual variability for VNT and CPR abundances suggest differences in the dynamics of the near- and sub-surface components of the populations.
    Print ISSN: 1054-3139
    Electronic ISSN: 1095-9289
    Topics: Biology , Geosciences , Physics
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  • 6
    Publication Date: 2021-10-30
    Description: Mitigating bycatch of non-target fish species is a common objective in fisheries management that may be supported by the gathering of data from fishery observer programs and quantitative analysis of bycatch risk factors. We build three GLM models based on Chinese tuna longline fishery observer data in terms of analysis of total bycatch rate (TB rate), total bycatch ratio (TB ratio), and species-specific bycatch rate, respectively. The positive log-linear models assumed a Gaussian observation error model and a linear combination of categorical independent variables, including area, year, month, depth, and bycatch species. Results show that distributions of TB rate and TB ratio followed different trends and a latitudinal decrease was observed from both the northern and southern hemisphere of the equator. Comprehensively, the Pacific is a better place to fish compared to the Indian and Atlantic Oceans in terms of relatively lower TB rate and TB ratio. Fishing in open oceans can somehow avoid a high TB ratio than fishing in coastal waters. As a result, we recommend area 2SW, 2SE, 2 NW, 14SW, 14SE, and 14 NW as appropriate fishing ground for Albacore (Thunnus alalunga) while area 11N,  11S, 18SW, and 18SE to be appropriate fishing ground for fishing bigeye tuna (Thunnus obesus). Setting fishing gears deeper than 500 m would also help to get a low TB rate and TB ratio.
    Print ISSN: 1054-3139
    Electronic ISSN: 1095-9289
    Topics: Biology , Geosciences , Physics
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  • 7
    Publication Date: 2021-10-30
    Description: Extrachromosomal circular DNA (eccDNA) are present within all eukaryotic organisms and actively contribute to gene expression changes. MicroDNA (200-1000bp) are the most abundant type of eccDNA and can amplify tRNA, microRNA, and novel si-like RNA sequences. Due to the heterogeneity of microDNA and the limited technology to directly quantify circular DNA molecules, the specific DNA repair pathways that contribute to microDNA formation have not been fully elucidated. Using a sensitive and quantitative assay that quantifies eight known abundant microDNA, we report that microDNA levels are dependent on resection after double-strand DNA break (DSB) and repair by Microhomology Mediated End Joining (MMEJ). Further, repair of DSB without resection by canonical Non-Homologous End Joining (c-NHEJ) diminishes microDNA formation. MicroDNA levels are induced locally even by a single site-directed DSB, suggesting that excision of genomic DNA by two closely spaced DSB is not necessary for microDNA formation. Consistent with all this, microDNA levels accumulate as cells undergo replication in S-phase, when DNA breaks and repair are elevated, and microDNA levels are decreased if DNA synthesis is prevented. Thus, formation of microDNA occurs during the repair of endogenous or induced DNA breaks by resection-based DNA repair pathways.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 8
    Publication Date: 2021-10-30
    Description: Motivation Differential network inference is a fundamental and challenging problem to reveal gene interactions and regulation relationships under different conditions. Many algorithms have been developed for this problem; however, they do not consider the differences between the importance of genes, which may not fit the real-world situation. Different genes have different mutation probabilities, and the vital genes associated with basic life activities have less fault tolerance to mutation. Equally treating all genes may bias the results of differential network inference. Thus, it is necessary to consider the importance of genes in the models of differential network inference. Results Based on the Gaussian graphical model with adaptive gene importance regularization, we develop a novel importance-penalized joint graphical Lasso method, IPJGL, for differential network inference. The presented method is validated by the simulation experiments as well as the real datasets. Furthermore, to precisely evaluate the results of differential network inference, we propose a new metric named APC2 for the differential levels of gene pairs. We apply IPJGL to analyze the TCGA colorectal and breast cancer datasets and find some candidate cancer genes with significant survival analysis results, including SOST for colorectal cancer and RBBP8 for breast cancer. We also conduct further analysis based on the interactions in the Reactome database and confirm the utility of our method. Availability R source code of importance-penalized joint graphical lasso is freely available at https://github.com/Wu-Lab/IPJGL. Supplementary information Supplementary materials are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 9
    Publication Date: 2021-10-30
    Description: Canonical non-homologous end-joining (cNHEJ) is the prominent mammalian DNA double-strand breaks (DSBs) repair pathway operative throughout the cell cycle. Phosphorylation of Ku70 at ser27-ser33 (pKu70) is induced by DNA DSBs and has been shown to regulate cNHEJ activity, but the underlying mechanism remained unknown. Here, we established that following DNA damage induction, Ku70 moves from nucleoli to the sites of damage, and once linked to DNA, it is phosphorylated. Notably, the novel emanating functions of pKu70 are evidenced through the recruitment of RNA Pol II and concomitant formation of phospho-53BP1 foci. Phosphorylation is also a prerequisite for the dynamic release of Ku70 from the repair complex through neddylation-dependent ubiquitylation. Although the non-phosphorylable ala-Ku70 form does not compromise the formation of the NHEJ core complex per se, cells expressing this form displayed constitutive and stress-inducible chromosomal instability. Consistently, upon targeted induction of DSBs by the I-SceI meganuclease into an intrachromosomal reporter substrate, cells expressing pKu70, rather than ala-Ku70, are protected against the joining of distal DNA ends. Collectively, our results underpin the essential role of pKu70 in the orchestration of DNA repair execution in living cells and substantiated the way it paves the maintenance of genome stability.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 10
    Publication Date: 2021-10-30
    Description: Brain is the central organ of the nervous system and any brain disease can seriously affect human health. Here we present BrainBase (https://ngdc.cncb.ac.cn/brainbase), a curated knowledgebase for brain diseases that aims to provide a whole picture of brain diseases and associated genes. Specifically, based on manual curation of 2768 published articles along with information retrieval from several public databases, BrainBase features comprehensive collection of 7175 disease–gene associations spanning a total of 123 brain diseases and linking with 5662 genes, 16 591 drug–target interactions covering 2118 drugs/chemicals and 623 genes, and five types of specific genes in light of expression specificity in brain tissue/regions/cerebrospinal fluid/cells. In addition, considering the severity of glioma among brain tumors, the current version of BrainBase incorporates 21 multi-omics datasets, presents molecular profiles across various samples/conditions and identifies four groups of glioma featured genes with potential clinical significance. Collectively, BrainBase integrates not only valuable curated disease–gene associations and drug–target interactions but also molecular profiles through multi-omics data analysis, accordingly bearing great promise to serve as a valuable knowledgebase for brain diseases.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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