The UCSC Genome Browser (https://genome.ucsc.edu) is an omics data consolidator, graphical viewer, and general bioinformatics resource that continues to serve the community as it enters its 23rd ...year. This year has seen an emphasis in clinical data, with new tracks and an expanded Recommended Track Sets feature on hg38 as well as the addition of a single cell track group. SARS-CoV-2 continues to remain a focus, with regular annotation updates to the browser and continued curation of our phylogenetic sequence placing tool, hgPhyloPlace, whose tree has now reached over 12M sequences. Our GenArk resource has also grown, offering over 2500 hubs and a system for users to request any absent assemblies. We have expanded our bigBarChart display type and created new ways to visualize data via bigRmsk and dynseq display. Displaying custom annotations is now easier due to our chromAlias system which eliminates the requirement for renaming sequence names to the UCSC standard. Users involved in data generation may also be interested in our new tools and trackDb settings which facilitate the creation and display of their custom annotations.
Abstract
The UCSC Genome Browser, https://genome.ucsc.edu, is a graphical viewer for exploring genome annotations. The website provides integrated tools for visualizing, comparing, analyzing, and ...sharing both publicly available and user-generated genomic datasets. Data highlights this year include a collection of easily accessible public hub assemblies on new organisms, now featuring BLAT alignment and PCR capabilities, and new and updated clinical tracks (gnomAD, DECIPHER, CADD, REVEL). We introduced a new Track Sets feature and enhanced variant displays to aid in the interpretation of clinical data. We also added a tool to rapidly place new SARS-CoV-2 genomes in a global phylogenetic tree enabling researchers to view the context of emerging mutations in our SARS-CoV-2 Genome Browser. Other new software focuses on usability features, including more informative mouseover displays and new fonts.
Abstract
For more than two decades, the UCSC Genome Browser database (https://genome.ucsc.edu) has provided high-quality genomics data visualization and genome annotations to the research community. ...As the field of genomics grows and more data become available, new modes of display are required to accommodate new technologies. New features released this past year include a Hi-C heatmap display, a phased family trio display for VCF files, and various track visualization improvements. Striving to keep data up-to-date, new updates to gene annotations include GENCODE Genes, NCBI RefSeq Genes, and Ensembl Genes. New data tracks added for human and mouse genomes include the ENCODE registry of candidate cis-regulatory elements, promoters from the Eukaryotic Promoter Database, and NCBI RefSeq Select and Matched Annotation from NCBI and EMBL-EBI (MANE). Within weeks of learning about the outbreak of coronavirus, UCSC released a genome browser, with detailed annotation tracks, for the SARS-CoV-2 RNA reference assembly.
Abstract
The UCSC Genome Browser (https://genome.ucsc.edu) provides a web interface for exploring annotated genome assemblies. The assemblies and annotation tracks are updated on an ongoing basis-12 ...assemblies and more than 28 tracks were added in the past year. Two recent additions are a display of CRISPR/Cas9 guide sequences and an interactive navigator for gene interactions. Other upgrades from the past year include a command-line version of the Variant Annotation Integrator, support for Human Genome Variation Society variant nomenclature input and output, and a revised highlighting tool that now supports multiple simultaneous regions and colors.
UCSC Genome Browser enters 20th year Lee, Christopher M; Barber, Galt P; Casper, Jonathan ...
Nucleic acids research,
01/2020, Letnik:
48, Številka:
D1
Journal Article
Recenzirano
Odprti dostop
Abstract
The University of California Santa Cruz Genome Browser website (https://genome.ucsc.edu) enters its 20th year of providing high-quality genomics data visualization and genome annotations to ...the research community. In the past year, we have added a new option to our web BLAT tool that allows search against all genomes, a single-cell expression viewer (https://cells.ucsc.edu), a ‘lollipop’ plot display mode for high-density variation data, a RESTful API for data extraction and a custom-track backup feature. New datasets include Tabula Muris single-cell expression data, GeneHancer regulatory annotations, The Cancer Genome Atlas Pan-Cancer variants, Genome Reference Consortium Patch sequences, new ENCODE transcription factor binding site peaks and clusters, the Database of Genomic Variants Gold Standard Variants, Genomenon Mastermind variants and three new multi-species alignment tracks.
Sirt3 is an NAD(+)-dependent deacetylase that regulates mitochondrial function by targeting metabolic enzymes and proteins. In fasting mice, Sirt3 expression is decreased in skeletal muscle resulting ...in increased mitochondrial protein acetylation. Deletion of Sirt3 led to impaired glucose oxidation in muscle, which was associated with decreased pyruvate dehydrogenase (PDH) activity, accumulation of pyruvate and lactate metabolites, and an inability of insulin to suppress fatty acid oxidation. Antibody-based acetyl-peptide enrichment and mass spectrometry of mitochondrial lysates from WT and Sirt3 KO skeletal muscle revealed that a major target of Sirt3 deacetylation is the E1α subunit of PDH (PDH E1α). Sirt3 knockout in vivo and Sirt3 knockdown in myoblasts in vitro induced hyperacetylation of the PDH E1α subunit, altering its phosphorylation leading to suppressed PDH enzymatic activity. The inhibition of PDH activity resulting from reduced levels of Sirt3 induces a switch of skeletal muscle substrate utilization from carbohydrate oxidation toward lactate production and fatty acid utilization even in the fed state, contributing to a loss of metabolic flexibility. Thus, Sirt3 plays an important role in skeletal muscle mitochondrial substrate choice and metabolic flexibility in part by regulating PDH function through deacetylation.
Abstract
The UCSC Genome Browser (https://genome.ucsc.edu) is a graphical viewer for exploring genome annotations. For almost two decades, the Browser has provided visualization tools for genetics ...and molecular biology and continues to add new data and features. This year, we added a new tool that lets users interactively arrange existing graphing tracks into new groups. Other software additions include new formats for chromosome interactions, a ChIP-Seq peak display for track hubs and improved support for HGVS. On the annotation side, we have added gnomAD, TCGA expression, RefSeq Functional elements, GTEx eQTLs, CRISPR Guides, SNPpedia and created a 30-way primate alignment on the human genome. Nine assemblies now have RefSeq-mapped gene models.
Abstract
The UCSC Genome Browser (https://genome.ucsc.edu) is a web-based genomic visualization and analysis tool that serves data to over 7,000 distinct users per day worldwide. It provides ...annotation data on thousands of genome assemblies, ranging from human to SARS-CoV2. This year, we have introduced new data from the Human Pangenome Reference Consortium and on viral genomes including SARS-CoV2. We have added 1,200 new genomes to our GenArk genome system, increasing the overall diversity of our genomic representation. We have added support for nine new user-contributed track hubs to our public hub system. Additionally, we have released 29 new tracks on the human genome and 11 new tracks on the mouse genome. Collectively, these new features expand both the breadth and depth of the genomic knowledge that we share publicly with users worldwide.
Graphical Abstract
Graphical Abstract
There has been concern that exposure to lithium early in pregnancy may be associated with a marked increase in the risk of Ebstein's anomaly (a right ventricular outflow tract obstruction defect) in ...infants and overall congenital cardiac defects, but data are conflicting and limited.
We conducted a cohort study involving 1,325,563 pregnancies in women who were enrolled in Medicaid and who delivered a live-born infant between 2000 and 2010. We examined the risk of cardiac malformations among infants exposed to lithium during the first trimester as compared with unexposed infants and, in secondary analyses, with infants exposed to another commonly used mood stabilizer, lamotrigine. Risk ratios and 95% confidence intervals were estimated with control for psychiatric and medical conditions, medications, and other potential confounders.
Cardiac malformations were present in 16 of the 663 infants exposed to lithium (2.41%), 15,251 of the 1,322,955 nonexposed infants (1.15%), and 27 of the 1945 infants exposed to lamotrigine (1.39%). The adjusted risk ratio for cardiac malformations among infants exposed to lithium as compared with unexposed infants was 1.65 (95% confidence interval CI, 1.02 to 2.68). The risk ratio was 1.11 (95% CI, 0.46 to 2.64) for a daily dose of 600 mg or less, 1.60 (95% CI, 0.67 to 3.80) for 601 to 900 mg, and 3.22 (95% CI, 1.47 to 7.02) for more than 900 mg. The prevalence of right ventricular outflow tract obstruction defects was 0.60% among lithium-exposed infants versus 0.18% among unexposed infants (adjusted risk ratio, 2.66; 95% CI, 1.00 to 7.06). Results were similar when lamotrigine-exposed infants were used as the reference group.
Maternal use of lithium during the first trimester was associated with an increased risk of cardiac malformations, including Ebstein's anomaly; the magnitude of this effect was smaller than had been previously postulated. (Funded by the National Institute of Mental Health.).
Diabetes strongly impacts protein metabolism, particularly in skeletal muscle. Insulin and IGF-1 enhance muscle protein synthesis through their receptors, but the relative roles of each in muscle ...proteostasis have not been fully elucidated. Using mice with muscle-specific deletion of the insulin receptor (M-IR-/- mice), the IGF-1 receptor (M-IGF1R-/- mice), or both (MIGIRKO mice), we assessed the relative contributions of IR and IGF1R signaling to muscle proteostasis. In differentiated muscle, IR expression predominated over IGF1R expression, and correspondingly, M-IR-/- mice displayed a moderate reduction in muscle mass whereas M-IGF1R-/- mice did not. However, these receptors serve complementary roles, such that double-knockout MIGIRKO mice displayed a marked reduction in muscle mass that was linked to increases in proteasomal and autophagy-lysosomal degradation, accompanied by a high-protein-turnover state. Combined muscle-specific deletion of FoxO1, FoxO3, and FoxO4 in MIGIRKO mice reversed increased autophagy and completely rescued muscle mass without changing proteasomal activity. These data indicate that signaling via IR is more important than IGF1R in controlling proteostasis in differentiated muscle. Nonetheless, the overlap of IR and IGF1R signaling is critical to the regulation of muscle protein turnover, and this regulation depends on suppression of FoxO-regulated, autophagy-mediated protein degradation.
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