Disease and phenotype data at Ensembl.

The Financial Industry's Plan for Resolving Failed Megabanks Will Ensure Future Bailouts for Wall Street

The 2023 Nucleic Acids Research Database Issue contains 178 papers ranging across biology and related fields. There are 90 papers reporting on new databases and 82 updates from resources previously published in the Issue. Six more papers are updates from databases most recently published elsewhere. Major nucleic acid databases reporting updates include Genbank, ENA, ChIPBase, JASPAR, mirDIP and the Issue's first Breakthrough Article, NACDDB for Circular Dichroism data. Updates from BMRB and RCSB cover experimental protein structural data while AlphaFold 2 computational structure predictions feature widely. STRING and REBASE are stand-out updates in the signalling and enzymes section. Immunology-related databases include CEDAR, the second Breakthrough Article, for cancer epitopes and receptors alongside returning IPD-IMGT/HLA and the new PGG.MHC. Genomics-related resources include Ensembl, GWAS Central and UCSC Genome Browser. Major returning databases for drugs and their targets include Open Targets, DrugCentral, CTD and Pubchem. The EMPIAR image archive appears in the Issue for the first time. The entire database Issue is freely available online on the Nucleic Acids Research website (https://academic.oup.com/nar). The NAR online Molecular Biology Database Collection has been updated, revisiting 463 entries, adding 92 new resources and eliminating 96 discontinued URLs so bringing the current total to 1764 databases. It is available at http://www.oxfordjournals.org/nar/database/c/.

Begun with Kasturba Medical College, Manipal, India in 1953, Manipal University Health Sciences Library, India is one of the largest libraries in South East Asia. Library offers a rich array of information resources for pursuing discovery and research. The library has access to variety of e-resources, including 18 online databases, more than 2500 online journals and e-books which have been made available to library users via various interfaces. Frustrated with navigating these different interfaces, Manipal University became aware of the fact that Health Sciences Library required a solution to access all library e-resources from a single entry point. This paper goes into the details on the ERMSS software which has provided library users with a single point access for effective searching of e-resources held by library. ERMSS meets the challenge with a feature-rich system combined with a robust administrative module and enabling a single point of access to entire e-resource collection of the library.

Many patients suffering from developmental disorders have submicroscopic deletions or duplications affecting the copy number of dosage-sensitive genes or disrupting normal gene expression. Many of these changes are novel or extremely rare, making clinical interpretation problematic and genotype/phenotype correlations difficult. Identification of patients sharing a genomic rearrangement and having phenotypes in common increases certainty in the diagnosis and allows characterization of new syndromes. The DECIPHER database is an online repository of genotype and phenotype data whose chief objective is to facilitate the association of genomic variation with phenotype to enable the clinical interpretation of copy number variation (CNV). This unit shows how DECIPHER can be used to (1) search for consented patients sharing a defined chromosomal location, (2) navigate regions of interest using in-house visualization tools and the Ensembl genome browser, (3) analyze affected genes and prioritize them according to their likelihood of haploinsufficiency, (4) upload patient aberrations and phenotypes, and (5) create printouts at different levels of detail. By following this protocol, clinicians and researchers alike will be able to learn how to characterize their patients' chromosomal imbalances using DECIPHER.

PhytoPath (www.phytopathdb.org) is a resource for genomic and phenotypic data from plant pathogen species, that integrates phenotypic data for genes from PHI-base, an expertly curated catalog of genes with experimentally verified pathogenicity, with the Ensembl tools for data visualization and analysis. The resource is focused on fungi, protists (oomycetes) and bacterial plant pathogens that have genomes that have been sequenced and annotated. Genes with associated PHI-base data can be easily identified across all plant pathogen species using a BioMart-based query tool and visualized in their genomic context on the Ensembl genome browser. The PhytoPath resource contains data for 135 genomic sequences from 87 plant pathogen species, and 1364 genes curated for their role in pathogenicity and as targets for chemical intervention. Support for community annotation of gene models is provided using the WebApollo online gene editor, and we are working with interested communities to improve reference annotation for selected species.

Most recent regulations establish that resolution of global banking groups shall be done according to bail-in procedures and following a Single Point of Entry (SPE) as opposed to a Multiple Point of Entry (MPE) approach. The latter requires parent holding of global groups to put up front the equity capital needed to absorb losses possibly emerging in foreign subsidiaries-branches. No model rationalized so far such resolution regime. We build a model of optimal design of resolution regimes and compare three regimes: SPE with cooperative authorities, SPE with non-cooperative authorities and MPE (ring-fencing). We find that the costs for bondholders of bail-inable instruments is generally higher under noncooperative regimes and ring-fencing. We also find that in those cases banks have ex ante incentives to reduce their exposure in foreign assets. We also examine recent case studies that help us rationalize the model results.

Danio rerio is a model organism used to investigate vertebrate development. Manipulation of the zebrafish genome and resultant gene products by mutation or targeted knockdown has made the zebrafish a good system for investigating gene function, providing a resource to investigate genetic contributors to phenotype and human disease. Phenotypic outcomes can be the result of gene mutation, targeted knockdown of gene products, manipulation of experimental conditions, or any combination thereof. Zebrafish have been used in various genetic and chemical screens to identify genetic and environmental contributors to phenotype and disease outcomes. The Zebrafish Information Network (ZFIN, zfin.org) is the central repository for genetic, genomic, and phenotypic data that result from research using D. rerio. Here we describe how ZFIN annotates phenotype, expression, and disease model data across various experimental designs, how we computationally determine wild-type gene expression, the phenotypic gene, and how these results allow us to propagate gene expression, phenotype, and disease model data to the correct gene, or gene related entity.

BackgroundAs large genomics and phenotypic datasets are becoming more common, it is increasingly difficult for most researchers to access, manage, and analyze them. One possible approach is to provide the research community with several petabyte-scale cloud-based computing platforms containing these data, along with tools and resources to analyze it.MethodsBionimbus is an open source cloud-computing platform that is based primarily upon OpenStack, which manages on-demand virtual machines that provide the required computational resources, and GlusterFS, which is a high-performance clustered file system. Bionimbus also includes Tukey, which is a portal, and associated middleware that provides a single entry point and a single sign on for the various Bionimbus resources; and Yates, which automates the installation, configuration, and maintenance of the software infrastructure required.ResultsBionimbus is used by a variety of projects to process genomics and phenotypic data. For example, it is used by an acute myeloid leukemia resequencing project at the University of Chicago. The project requires several computational pipelines, including pipelines for quality control, alignment, variant calling, and annotation. For each sample, the alignment step requires eight CPUs for about 12 h. BAM file sizes ranged from 5 GB to 10 GB for each sample.ConclusionsMost members of the research community have difficulty downloading large genomics datasets and obtaining sufficient storage and computer resources to manage and analyze the data. Cloud computing platforms, such as Bionimbus, with data commons that contain large genomics datasets, are one choice for broadening access to research data in genomics.

As a result of the advent of high-throughput technologies, there has been rapid progress in our understanding of the genetics underlying biological processes. However, despite such advances, the genetic landscape of human diseases has only marginally been disclosed. Exploiting the present availability of large amounts of biological and phenotypic data, we can use our current understanding of disease genetics to train machine learning models to predict novel genetic factors associated with the disease. To this end, we developed DGLinker, a webserver for the prediction of novel candidate genes for human diseases given a set of known disease genes. DGLinker has a user-friendly interface that allows non-expert users to exploit biomedical information from a wide range of biological and phenotypic databases, and/or to upload their own data, to generate a knowledge-graph and use machine learning to predict new disease-associated genes. The webserver includes tools to explore and interpret the results and generates publication-ready figures. DGLinker is available at https://dglinker.rosalind.kcl.ac.uk. The webserver is free and open to all users without the need for registration.

Repulsive guidance molecules, RGMA, RGMB, and RGMC, are related proteins discovered independently through different experimental paradigms. They are encoded by single copy genes in mammalian and other vertebrate genomes, and are ~50% identical in amino acid sequence. The importance of RGM actions in human physiology has not been realized, as most research has focused on non‐human models, although mutations in RGMC are the cause of the severe iron storage disorder, juvenile hemochromatosis. Here I show that repositories of human genomic and population genetic data can be used as starting points for discovery and for developing new testable hypotheses about each of these paralogs in human biology and disease susceptibility. Information was extracted, aggregated, and analyzed from the Ensembl and UCSC Genome Browsers, the Exome Aggregation Consortium, the Genotype‐Tissue Expression project portal, the cBio portal for Cancer Genomics, and the National Cancer Institute Genomic Data Commons data site. Results identify extensive variation in gene expression patterns, substantial alternative RNA splicing, and possible missense alterations and other modifications in the coding regions of each of the three genes, with many putative mutations being detected in individuals with different types of cancers. Moreover, selected amino acid substitutions are highly prevalent in the world population, with minor allele frequencies of up to 37% for RGMA and up to 8% for RGMB. These results indicate that protein sequence variation is common in the human RGM family, and raises the possibility that individual variants will have a significant population impact on human physiology and/or disease predisposition.

The Act No. CCXXII. of 2015 on general rules of electronic administration and trust services,(hereinafter ‘eAdministration Act’), defined the concept of customisable electronic administration user interface (hereinafter ‘SZÜF’). The purpose of establishing the SZÜF portal was to create a single gate entry point (as a starting page) for electronic administration of central and local government, linking the various IT systems of different institutions. The new customisable electronic administration user interface was launched in January 2018. According to the plans, it will shortly replace the former magyarorszag.hu portal as the point of single contact portal of Hungary. The new SZÜF portal has a more modern and pure design as well as a life-situation based approach to publish existing eGovernment services. The electronic administration services are available to the client after electronic identification and authentication by the Central Authentication Agent. Services can be used by natural persons (citizens) and organisations (including public administrations, businesses). The identified client can access their digital post-box, can manage their personal calendar, and can save their favourite services among the eGovernment services available on the portal. The SZÜF portal provides infrastructure and applications services to the connected organisations supporting the electronic administration process. For the connected service providers (public administration bodies designated by eAdministration Act) the SZÜF provides specific content and service management solutions. These services may be integrated in the SZÜF or be outside the SZÜF. Currently there are big differences in the quality of services. As a first step, the collection of e-administration information and services was completed. The next task is to ensure uniformity, service-oriented platform and interoperability. The purpose of this study is to present the areas for further development of the services of the SZÜF portal while presenting the results achieved. Achieved goals: a single gate entry point for electronic services for natural persons and organizations on a customisable interface with new online request submission options (e-Paper, iForm). Further development is needed: unification, interoperability and integration of services, connection of additional organizations, possibility of situation-based administration.

Unconventional reservoirs require innovative completion techniques and technology to become more economical. Formations vary drastically in lithology, lateral lengths, completion methods, and financial drivers. Since reservoir conditions typically mandate the use of hydraulic fracturing for economical production results, a significant amount of resources are focused on making the fracturing process more efficient and lowering its environmental impact. This case history includes an operational review focused on a novel technique to rapidly perform targeted annular hydraulic fractures by deploying an activation tool on coiled tubing (CT) to open frac sleeves in a horizontal well. The paper covers results and information gathered from the first operation of its kind in Montana's Bakken Formation – where a total of 19 stages were fractured in the shaley dolomite. The new technology does not involve dropping balls or setting composite plugs to isolate stages. Rather, the technique utilizes frac sleeves that are activated using a CT bottomhole assembly to save time between stages. The sleeves can be cemented in place if desired and have a full-bore internal diameter that does not require post-treatment composite plug millouts, further reducing overall completion time and time to production. Additional capabilities of the system enable the use of memory gauges to monitor downhole pressure and temperature characteristics. The operator preferred this method due to its targeted nature, efficiency, and fluid savings. As opposed to multicluster fracturing methods (such as ‘plug-n-perf"), a single entry point during the frac job promotes increased fluid velocity, enabling a more aggressive sand ramp and reduction in required hydraulic horsepower. Similarly, the single entry point ensures that a fracture is generated at each port, as opposed to the possibility that some clusters are not treated. In addition, no composite plugs or diverting devices are required to be pumped down the wellbore, so water usage is reduced considerably. The system, already used in thousands of fracturing stages in Canada, speeds up the completion process, uses less fluid, minimizes risks, and reduces overall downtime.

There has been a booming interest in developing WiFi localization using multi-antenna (MIMO) access points (APs). Recent advances have demonstrated promising results that break the meter-accuracy barrier using commodity APs. Yet these state-of-the-art solutions require either multiple APs that are not necessarily available in practice, or multiple-channel measurements that disrupt normal data communication. In this paper, we present SiFi, a single AP-based indoor localization system that for the first time achieves sub-meter accuracy with a single channel only. The SiFi design is based on a key observation: with MIMO, the multiple (typically three) antennas of an AP are frequency-locked; although the accurate Time-of-Arrival (ToA) estimation on commodity APs is fundamentally limited by the imperfect time and frequency synchronization between the transmitter and receiver, there should be only one value for the ToA distortion that can cause three direct-path ToAs of the antennas to intersect at a single point, i.e., the position of the target. We develop the theoretical foundations of SiFi and demonstrate its realworld implementation with off-the-shelf WiFi cards. Our implementation introduces no hardware modification and is fully compatible with concurrent data transmission. It achieves a median accuracy of 0.93 m, which significantly outperforms the best known single AP single channel solution.

In single-port surgery, the surgeon operates almost exclusively through a single entry point, typically the patient's navel, leaving only a single small scar. The aims of this study were to share some tips and tricks of single-port robotic-assisted sacrocolpopexy and to evaluate the learning curve of mastering the skills to operate this procedure. This is a retrospective study of the first 25 single-port; robotic-assisted sacrocolpopexy surgeries performed during July to December 2015 at Rambam Health Care Campus by a single surgeon.Primary points of interest included intraoperative bleeding, length of surgery, length of hospitalization, and surgical complications. The median age was 59 years (range, 35-74); the median "pelvic organ prolapse quantification" stage was 3 (range, 2-4). The median total operative time was 190 minutes (range, 114-308), and console time was 130 minutes (85-261). Comparisons between the first 15 cases and the following 10 cases demonstrated significant decreases in median total operative and console times: 226 minutes (range, 142-308) versus 156 minutes (range, 114-180), and 170 minutes (range, 85-261) versus 115 minutes (range, 90-270), respectively (P < 0.008). There were no intraoperative adverse events. Postoperative adverse events were also rare, including 1 case of small bowel adhesions that required a second laparoscopic surgery for adhesiolysis. After this incident, we peritonalized the mesh in all 13 successive cases; median time was 8 minutes (range, 5-15 minutes). Single-port robotic-assisted sacrocolpopexy is a feasible procedure with low complication rates, minimal blood loss and postsurgical pain, fast recovery, short hospitalization, and virtually scar-free results. Outcomes of long-term follow-up should be investigated.

Steerability in percutaneous medical devices is highly desirable, enabling a needle or needle-like instrument to avoid sensitive structures (e.g. nerves or blood vessels), access obstructed anatomical targets, and compensate for the inevitable errors induced by registration accuracy thresholds and tissue deformation during insertion. Thus, mechanisms for needle steering have been of great interest in the engineering community in the past few years, and several have been proposed. While many interventional applications have been hypothesized for steerable needles (essentially anything deliverable via a regular needle), none have yet been demonstrated as far as the authors are aware. Instead, prior studies have focused on model validation, control, and accuracy assessment. In this paper, we present the first integrated steerable needle-interventional device. The ACUSITT integrates a multi-tube steerable Active Cannula (AC) with an Ultrasonic Interstitial Thermal Therapy ablator (USITT) to create a steerable percutaneous device that can deliver a spatially and temporally controllable (both mechanically and electronically) thermal dose profile. We present our initial experiments toward applying the ACUSITT to treat large liver tumors through a single entry point. This involves repositioning the ablator tip to several different locations, without withdrawing it from the liver capsule, under 3D Ultrasound image guidance. In our experiments, the ACUSITT was deployed to three positions, each 2cm apart in a conical pattern to demonstrate the feasibility of ablating large liver tumors 7cm in diameter without multiple parenchyma punctures.