The Year of the Rat: The Rat Genome Database at 20: a multi-species knowledgebase and analysis platform.

Formed in late 1999, the Rat Genome Database (RGD, https://rgd.mcw.edu) will be 20 in 2020, the Year of the Rat. Because the laboratory rat, Rattus norvegicus, has been used as a model for complex human diseases such as cardiovascular disease, diabetes, cancer, neurological disorders and arthritis, among others, for >150 years, RGD has always been disease-focused and committed to providing data and tools for researchers doing comparative genomics and translational studies. At its inception, before the sequencing of the rat genome, RGD started with only a few data types localized on genetic and radiation hybrid (RH) maps and offered only a few tools for querying and consolidating that data. Since that time, RGD has expanded to include a wealth of structured and standardized genetic, genomic, phenotypic, and disease-related data for eight species, and a suite of innovative tools for querying, analyzing and visualizing this data. This article provides an overview of recent substantial additions and improvements to RGD's data and tools that can assist researchers in finding and utilizing the data they need, whether their goal is to develop new precision models of disease or to more fully explore emerging details within a system or across multiple systems.

Deletion 20q12 is associated with histological transformation of nodal marginal zone lymphoma to diffuse large B-cell lymphoma.

The genetic and molecular abnormalities underlying histological transformation (HT) of nodal marginal zone lymphoma (NMZL) to diffuse large B-cell lymphoma (DLBCL) are not well known. While del(20q12) is commonly deleted in myelodysplastic syndrome it has not previously been associated with DLBCL. We recently described a case of DLBCL harboring del(20q12) in a patient with a history of MZL involving lymph nodes and skin. Here we report eight matched cases of transformed MZL(tMZL): six from nodal MZL (tNMZL) and two from splenic MZL (tSMZL). We found >20% del(20q12) in 4/6 tNMZL, but not in tSMZL, nor in unmatched DLBCL, MZL with increased large cells (MZL-ILC), or MZL cases. To examine whether transformation is associated with a specific gene signature, the matched cases were analyzed for multiplexed gene expression using the Nanostring PanCancer Pathways panel. The differential gene expression signature revealed enrichment of inflammatory markers, as previously observed in MZL. Also, tMZL and de novo DLBCL were enriched for extracellular matrix proteins such as collagen and fibronectin, vascular development protein PDGFRß, DNA repair protein RAD51, and oncogenic secrete protein Wnt11. A subset of genes is expressed differentially in del(20q12) tMZL cases vs non-del(20q12) tMZL cases. These results suggest a specific pathway is involved in the histological transformation of NMZL, which could serve as an indicator of aggressive clinical course in this otherwise indolent neoplasm.

Barriers and Facilitators to Help-Seeking for Individuals With Posttraumatic Stress Disorder: A Systematic Review.

Posttraumatic stress disorder (PTSD) brings with it diagnostic symptoms that can be debilitating and persist for years. Left untreated, PTSD can have far-reaching and damaging consequences for the individual, families, communities, and society at large. Although early detection and intervention are recognized as key to the effective treatment of PTSD, many individuals who suffer from PTSD do not seek essential health services. The aim of the present study was to identify the barriers and facilitators to help-seeking for individuals with PTSD, based on existing literature. A systematic review, modeled on the Joanna Briggs Institute methodology for systematic reviews, examined studies cited in PsycINFO, Medline, Embase, CINAHL, and PILOTS published from January 1980 to January 2019. Eligible studies measured barriers and facilitators to help-seeking for adults with PTSD. Two reviewers independently screened citations, and double data extraction was exercised. Of 2,391 potentially relevant citations, 21 studies, published between 1989 and 2018 and based in six countries, were included. Seventeen studies focused on military as a target population. We identified 10 principal barrier and facilitator themes: trauma-related; treatment; therapist or provider; knowledge; access; health care system; sociocultural environment; values, beliefs, and priorities; past experiences; and medical care needs and illness burden. In identifying prominent barriers and facilitators to help-seeking for individuals with PTSD, this review highlights opportunities to inform policies and programs that promote PTSD knowledge and recognition, reduce public and personal stigma, improve access and quality of care, and encourage support for patients and families living with PTSD.

Early emergence of anti-HCV antibody implicates donor origin in recipients of an HCV-infected organ.

Hepatitis C virus (HCV) seroconversion among HCV-uninfected transplant recipients from HCV-infected (NAT+/Antibody+) or HCV-exposed (NAT-/Antibody+) donors has been reported. However, the origin of anti-HCV antibody and the implications of seroconversion remain unknown. We longitudinally tested plasma from HCV-uninfected kidney (n = 31) or heart transplant recipients (n = 9) of an HCV NAT+ organ for anti-HCV antibody (both IgG and IgM isotypes). Almost half of all participants had detectable anti-HCV antibody at any point during follow-up. The majority of antibody-positive individuals became positive within 1-3 days of transplantation, and 6 recipients had detectable antibody on the first day posttransplant. Notably, all anti-HCV antibody was IgG, even in samples collected posttransplant day 1. Late seroconversion was uncommon (≈20%-25% of antibody+ recipients). Early antibody persisted over 30 days in kidney recipients, whereas early antibody dropped below detection in 50% of heart recipients within 2 weeks after transplant. Anti-HCV antibody is common in HCV-uninfected recipients of an HCV NAT+ organ. The IgG isotype of this antibody and the kinetics of its appearance and durability suggest that anti-HCV antibody is donor derived and is likely produced by a cellular source. Our data suggest that transfer of donor humoral immunity to a recipient may be much more common than previously appreciated.

Guidelines for the functional annotation of microRNAs using the Gene Ontology.

MicroRNA regulation of developmental and cellular processes is a relatively new field of study, and the available research data have not been organized to enable its inclusion in pathway and network analysis tools. The association of gene products with terms from the Gene Ontology is an effective method to analyze functional data, but until recently there has been no substantial effort dedicated to applying Gene Ontology terms to microRNAs. Consequently, when performing functional analysis of microRNA data sets, researchers have had to rely instead on the functional annotations associated with the genes encoding microRNA targets. In consultation with experts in the field of microRNA research, we have created comprehensive recommendations for the Gene Ontology curation of microRNAs. This curation manual will enable provision of a high-quality, reliable set of functional annotations for the advancement of microRNA research. Here we describe the key aspects of the work, including development of the Gene Ontology to represent this data, standards for describing the data, and guidelines to support curators making these annotations. The full microRNA curation guidelines are available on the GO Consortium wiki (http://wiki.geneontology.org/index.php/MicroRNA_GO_annotation_manual).

The effectiveness of the food and beverage industry's self-established uniform nutrition criteria at improving the healthfulness of food advertising viewed by Canadian children on television.

BACKGROUND: Food and beverage marketing has been identified as an environmental determinant of childhood obesity. The purpose of this study is to assess whether the Uniform Nutrition Criteria established and implemented by companies participating in the self-regulatory Canadian Children's Food and Beverage Advertising Initiative (CAI) had an impact on the healthfulness of food and beverage advertising during television programming with a high share of children in the viewing audience. METHODS: Data on food advertising were licensed from Numeris for 27 television stations for Toronto for May 2013 and May 2016 (i.e. before and after the implementation of the nutrition criteria). First, television programs that had a child audience share of ≥35% (when the nutrition criteria applied) were identified. Ten percent of these programs were randomly selected and included in the study. After identifying the food and beverage ads that aired during these programs, the nutritional information of advertised products was collected and their healthfulness was assessed using the Pan-American Health Organization (PAHO) and UK Nutrient Profile Models (NPM). The healthfulness of CAI products advertised in May 2013 and 2016 was compared using Chi-square tests. RESULTS: Although in May 2016, products advertised by CAI companies were more likely to be categorized as healthier by the UK NPM (21.5% versus 6.7%, χ2(1) = 12.1,p = 000) compared to those advertised in May 2013, the frequency of advertised products considered less healthy in May 2016 remained very high (78.5%) and comparable to that of products advertised by companies not participating in the CAI (80.0% categorized as less healthy). Furthermore, in both May 2013 and May 2016, 99-100% of CAI advertisements featured products deemed excessive in either fat (total, saturated, trans), sodium or free sugars according to the PAHO NPM. CONCLUSIONS: Despite modest improvements noted after the implementation of the CAI's Uniform Nutrition Criteria, the healthfulness of most products advertised during programs with a high share of children in the viewing audience remains poor. Mandatory regulations are needed.

Expediting Formulary Standardization in a Multihospital Health System Using Layered Learners.

Drug formularies are a necessary part of medication management in hospitals and health systems. The system-level P&T committee at BJC HealthCare, a multihospital health system in St. Louis, Missouri, developed an approach to standardization of a system-wide formulary using available layered learners to complete the work in an expedited manner before implementation of a system-wide electronic medical record. The formulary standardization work was allocated to reviewers-including pharmacy students, residents, clinical pharmacy specialists, and pharmacy leadership-according to the complexity of the drug class under review, and a pharmacist was assigned to oversee and support the learner (student or resident) as class reviews were performed. The reviewer prepared a review of the drug class, developed recommendations for formulary agents and therapeutic interchanges, and presented recommendations to key stakeholder groups in the organization before a final decision by the system P&T committee. Using this approach, 27 therapeutic class reviews were conducted in 15 months, and 153 of 346 individual agents reviewed (44%) were retained on the formulary. The alignment of formulary medications and interchanges in the 27 classes resulted in an estimated $1.185 million savings in supply costs in the 12 months after implementing the changes. Standardization of the formulary and therapeutic interchanges can be expedited by using a layered learner model, and this model can be used in other health systems to accelerate the formulary review process.

Short-term, high-fat overfeeding impairs glycaemic control but does not alter gut hormone responses to a mixed meal tolerance test in healthy, normal-weight individuals.

Obesity is undoubtedly caused by a chronic positive energy balance. However, the early metabolic and hormonal responses to overeating are poorly described. This study determined glycaemic control and selected gut hormone responses to nutrient intake before and after 7 d of high-fat overfeeding. Nine healthy individuals (five males, four females) performed a mixed meal tolerance test (MTT) before and after consuming a high-fat (65 %), high-energy (+50 %) diet for 7 d. Measurements of plasma glucose, NEFA, acylated ghrelin, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP) and serum insulin were taken before (fasting) and at 30-min intervals throughout the 180-min MTT (postprandial). Body mass increased by 0·79 (sem 0·14) kg after high-fat overfeeding (P<0·0001), and BMI increased by 0·27 (sem 0·05) kg/m2 (P=0·002). High-fat overfeeding also resulted in an 11·6 % increase in postprandial glucose AUC (P=0·007) and a 25·9 % increase in postprandial insulin AUC (P=0·005). Acylated ghrelin, GLP-1 and GIP responses to the MTT were all unaffected by the high-fat, high-energy diet. These findings demonstrate that even brief periods of overeating are sufficient to disrupt glycaemic control. However, as the postprandial orexigenic (ghrelin) and anorexigenic/insulintropic (GLP-1 and GIP) hormone responses were unaffected by the diet intervention, it appears that these hormones are resistant to short-term changes in energy balance, and that they do not play a role in the rapid reduction in glycaemic control.

The Rat Genome Database 2015: genomic, phenotypic and environmental variations and disease.

The Rat Genome Database (RGD, http://rgd.mcw.edu) provides the most comprehensive data repository and informatics platform related to the laboratory rat, one of the most important model organisms for disease studies. RGD maintains and updates datasets for genomic elements such as genes, transcripts and increasingly in recent years, sequence variations, as well as map positions for multiple assemblies and sequence information. Functional annotations for genomic elements are curated from published literature, submitted by researchers and integrated from other public resources. Complementing the genomic data catalogs are those associated with phenotypes and disease, including strains, QTL and experimental phenotype measurements across hundreds of strains. Data are submitted by researchers, acquired through bulk data pipelines or curated from published literature. Innovative software tools provide users with an integrated platform to query, mine, display and analyze valuable genomic and phenomic datasets for discovery and enhancement of their own research. This update highlights recent developments that reflect an increasing focus on: (i) genomic variation, (ii) phenotypes and diseases, (iii) data related to the environment and experimental conditions and (iv) datasets and software tools that allow the user to explore and analyze the interactions among these and their impact on disease.

Comprehensive coverage of cardiovascular disease data in the disease portals at the Rat Genome Database.

Cardiovascular diseases are complex diseases caused by a combination of genetic and environmental factors. To facilitate progress in complex disease research, the Rat Genome Database (RGD) provides the community with a disease portal where genome objects and biological data related to cardiovascular diseases are systematically organized. The purpose of this study is to present biocuration at RGD, including disease, genetic, and pathway data. The RGD curation team uses controlled vocabularies/ontologies to organize data curated from the published literature or imported from disease and pathway databases. These organized annotations are associated with genes, strains, and quantitative trait loci (QTLs), thus linking functional annotations to genome objects. Screen shots from the web pages are used to demonstrate the organization of annotations at RGD. The human cardiovascular disease genes identified by annotations were grouped according to data sources and their annotation profiles were compared by in-house tools and other enrichment tools available to the public. The analysis results show that the imported cardiovascular disease genes from ClinVar and OMIM are functionally different from the RGD manually curated genes in terms of pathway and Gene Ontology annotations. The inclusion of disease genes from other databases enriches the collection of disease genes not only in quantity but also in quality.

Hsp90-dependent activation of protein kinases is regulated by chaperone-targeted dephosphorylation of Cdc37.

Activation of protein kinase clients by the Hsp90 system is mediated by the cochaperone protein Cdc37. Cdc37 requires phosphorylation at Ser13, but little is known about the regulation of this essential posttranslational modification. We show that Ser13 of uncomplexed Cdc37 is phosphorylated in vivo, as well as in binary complex with a kinase (C-K), or in ternary complex with Hsp90 and kinase (H-C-K). Whereas pSer13-Cdc37 in the H-C-K complex is resistant to nonspecific phosphatases, it is efficiently dephosphorylated by the chaperone-targeted protein phosphatase 5 (PP5/Ppt1), which does not affect isolated Cdc37. We show that Cdc37 and PP5/Ppt1 associate in Hsp90 complexes in yeast and in human tumor cells, and that PP5/Ppt1 regulates phosphorylation of Ser13-Cdc37 in vivo, directly affecting activation of protein kinase clients by Hsp90-Cdc37. These data reveal a cyclic regulatory mechanism for Cdc37, in which its constitutive phosphorylation is reversed by targeted dephosphorylation in Hsp90 complexes.

The Rat Genome Database 2013--data, tools and users.

The Rat Genome Database (RGD) was started >10 years ago to provide a core genomic resource for rat researchers. Currently, RGD combines genetic, genomic, pathway, phenotype and strain information with a focus on disease. RGD users are provided with access to structured and curated data from the molecular level through the organismal level. Those users access RGD from all over the world. End users are not only rat researchers but also researchers working with mouse and human data. Translational research is supported by RGD's comparative genetics/genomics data in disease portals, in GBrowse, in VCMap and on gene report pages. The impact of RGD also goes beyond the traditional biomedical researcher, as the influence of RGD reaches bioinformaticians, tool developers and curators. Import of RGD data into other publicly available databases expands the influence of RGD to a larger set of end users than those who avail themselves of the RGD website. The value of RGD continues to grow as more types of data and more tools are added, while reaching more types of end users.

Disease pathways at the Rat Genome Database Pathway Portal: genes in context-a network approach to understanding the molecular mechanisms of disease.

BACKGROUND: Biological systems are exquisitely poised to respond and adjust to challenges, including damage. However, sustained damage can overcome the ability of the system to adjust and result in a disease phenotype, its underpinnings many times elusive. Unraveling the molecular mechanisms of systems biology, of how and why it falters, is essential for delineating the details of the path(s) leading to the diseased state and for designing strategies to revert its progression. An important aspect of this process is not only to define the function of a gene but to identify the context within which gene functions act. It is within the network, or pathway context, that the function of a gene fulfills its ultimate biological role. Resolving the extent to which defective function(s) affect the proceedings of pathway(s) and how altered pathways merge into overpowering the system's defense machinery are key to understanding the molecular aspects of disease and envisioning ways to counteract it. A network-centric approach to diseases is increasingly being considered in current research. It also underlies the deployment of disease pathways at the Rat Genome Database Pathway Portal. The portal is presented with an emphasis on disease and altered pathways, associated drug pathways, pathway suites, and suite networks. RESULTS: The Pathway Portal at the Rat Genome Database (RGD) provides an ever-increasing collection of interactive pathway diagrams and associated annotations for metabolic, signaling, regulatory, and drug pathways, including disease and altered pathways. A disease pathway is viewed from the perspective of networks whose alterations are manifested in the affected phenotype. The Pathway Ontology (PW), built and maintained at RGD, facilitates the annotations of genes, the deployment of pathway diagrams, and provides an overall navigational tool. Pathways that revolve around a common concept and are globally connected are presented within pathway suites; a suite network combines two or more pathway suites. CONCLUSIONS: The Pathway Portal is a rich resource that offers a range of pathway data and visualization, including disease pathways and related pathway suites. Viewing a disease pathway from the perspective of underlying altered pathways is an aid for dissecting the molecular mechanisms of disease.

Exploring Care and Recovery for Individuals With Post-traumatic Stress Disorder: A Scoping Review.

Most people experience trauma at some point in their lives. The sources of trauma can include accidents, natural disasters, physical or sexual assault, combat, torture, or the death of a loved one. Experiencing or witnessing any of these, or other terrifying events, may make one susceptible to developing post-traumatic stress disorder (PTSD), a trauma- and stressor-related mental health condition. The common symptoms and consequences of PTSD include intrusive and distressing thoughts, memories, or flashbacks related to the traumatic event; avoidance of situations, people, or activities that remind one of the traumatic event; irritability, sleep difficulties, or hypervigilance; feelings of guilt, shame, or fear; substance use; strains on relationships; and suicidal thoughts and behaviors. These consequences can have devastating effects on the individual and their family members, friends, co-workers, peers, and communities. Effectively treating PTSD, therefore, is critical not only for the individual but also for the well-being of families, communities, and society at large. However, while treatments for PTSD exist, effectively treating patients with PTSD remains elusive. Further, despite the recognition that people's experiences are essential in understanding PTSD and provide valuable insights into what interventions are effective and how they impact recovery, patient perspectives and experiences of care and recovery have not been well-explored. We conducted a scoping review to address the following question: what is known about the experiences and perspectives of care and recovery for individuals with PTSD? We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE), Embase, American Psychological Association's (APA) PsycInfo, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PTSDPubs, and Google Scholar for peer-reviewed and grey literature that used qualitative methods to report on the recovery or care experiences of adults with lived experiences of PTSD. We extracted information about study objectives, study characteristics, and key findings; reported summary statistics; and performed content and thematic analyses. We identified 14 relevant studies that provide insight into the participants' lived experiences and perspectives of PTSD care and recovery. Though limited, the body of literature sheds light on critical themes and processes in the journey of care of PTSD, which we organized into four overarching categories: pre-treatment understanding and experiences of PTSD, the experience of care or treatment, the importance of relationships and social support, and expanding the understandings of recovery. Living with and healing from PTSD are a unique and individualized human experience of developing and redeveloping relationships with oneself, with others, and with society. The recommendations for practice include educating and establishing well-informed support networks for individuals with PTSD, training healthcare practitioners in all aspects of formal and informal PTSD treatment and care needs, ensuring a continuum of care, and understanding the human experience of PTSD.

A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats.

The seventh iteration of the reference genome assembly for Rattus norvegicus-mRatBN7.2-corrects numerous misplaced segments and reduces base-level errors by approximately 9-fold and increases contiguity by 290-fold compared with its predecessor. Gene annotations are now more complete, improving the mapping precision of genomic, transcriptomic, and proteomics datasets. We jointly analyzed 163 short-read whole-genome sequencing datasets representing 120 laboratory rat strains and substrains using mRatBN7.2. We defined ∼20.0 million sequence variations, of which 18,700 are predicted to potentially impact the function of 6,677 genes. We also generated a new rat genetic map from 1,893 heterogeneous stock rats and annotated transcription start sites and alternative polyadenylation sites. The mRatBN7.2 assembly, along with the extensive analysis of genomic variations among rat strains, enhances our understanding of the rat genome, providing researchers with an expanded resource for studies involving rats.

Rat Genome Database: a unique resource for rat, human, and mouse quantitative trait locus data.

The rat has been widely used as a disease model in a laboratory setting, resulting in an abundance of genetic and phenotype data from a wide variety of studies. These data can be found at the Rat Genome Database (RGD, http://rgd.mcw.edu/), which provides a platform for researchers interested in linking genomic variations to phenotypes. Quantitative trait loci (QTLs) form one of the earliest and core datasets, allowing researchers to identify loci harboring genes associated with disease. These QTLs are not only important for those using the rat to identify genes and regions associated with disease, but also for cross-organism analyses of syntenic regions on the mouse and the human genomes to identify potential regions for study in these organisms. Currently, RGD has data on >1,900 rat QTLs that include details about the methods and animals used to determine the respective QTL along with the genomic positions and markers that define the region. RGD also curates human QTLs (>1,900) and houses>4,000 mouse QTLs (imported from Mouse Genome Informatics). Multiple ontologies are used to standardize traits, phenotypes, diseases, and experimental methods to facilitate queries, analyses, and cross-organism comparisons. QTLs are visualized in tools such as GBrowse and GViewer, with additional tools for analysis of gene sets within QTL regions. The QTL data at RGD provide valuable information for the study of mapped phenotypes and identification of candidate genes for disease associations.

Prolonged infusion antibiotics for suspected gram-negative infections in the ICU: a before-after study.

BACKGROUND: ß-Lactam antibiotics demonstrate time-dependent killing. Prolonged infusion of these agents is commonly performed to optimize the time the unbound concentration of an antibiotic remains greater than the minimum inhibitory concentration and decrease costs, despite limited evidence suggesting improved clinical results. OBJECTIVE: To determine whether prolonged infusion of ß-lactam antibiotics improves outcomes in critically ill patients with suspected gram-negative infection. METHODS: We conducted a single-center, before-after, comparative effectiveness trial between January 2010 and January 2011 in the intensive care units at Barnes-Jewish Hospital, an urban teaching hospital affiliated with the Washington University School of Medicine in St. Louis, MO. Outcomes were compared between patients who received standardized dosing of meropenem, piperacillin-tazobactam, or cefepime as an intermittent infusion over 30 minutes (January 1, 2010, to June 30, 2010) and patients who received prolonged infusion over 3 hours (August 1, 2010, to January 31, 2011). RESULTS: A total of 503 patients (intermittent infusion, n = 242; prolonged infusion, n = 261) treated for gram-negative infection were included in the clinically evaluable population. Approximately 50% of patients in each group received cefepime and 20% received piperacillin-tazobactam. More patients in the intermittent infusion group received meropenem (35.5% vs 24.5%; p = 0.007). Baseline characteristics were similar between groups, with the exception of a greater occurrence of chronic obstructive pulmonary disease (COPD) in the intermittent infusion group. Treatment success rates in the clinically evaluable group were 56.6% for intermittent infusion and 51.0% for prolonged infusion (p = 0.204), and in the microbiologically evaluable population, 55.2% for intermittent infusion and 49.5% for prolonged infusion (p = 0.486). Fourteen-day, 30-day, and inhospital mortality rates in the clinically evaluable population for the intermittent and prolonged infusion groups were 13.2% versus 18.0% (p = 0.141), 23.6% versus 25.7% (p = 0.582), and 19.4% versus 23.0% (p = 0.329). CONCLUSIONS: Routine use of prolonged infusion of time-dependent antibiotics for the empiric treatment of gram-negative bacterial infections offers no advantage over intermittent infusion antibiotic therapy with regard to treatment success, mortality, or hospital length of stay. These results were confirmed after controlling for potential confounders in a multivariate analysis.

The Rat Genome Database: Genetic, Genomic, and Phenotypic Data Across Multiple Species.

The laboratory rat, Rattus norvegicus, is an important model of human health and disease, and experimental findings in the rat have relevance to human physiology and disease. The Rat Genome Database (RGD, https://rgd.mcw.edu) is a model organism database that provides access to a wide variety of curated rat data including disease associations, phenotypes, pathways, molecular functions, biological processes, cellular components, and chemical interactions for genes, quantitative trait loci, and strains. We present an overview of the database followed by specific examples that can be used to gain experience in employing RGD to explore the wealth of functional data available for the rat and other species. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Navigating the Rat Genome Database (RGD) home page Basic Protocol 2: Using the RGD search functions Basic Protocol 3: Searching for quantitative trait loci Basic Protocol 4: Using the RGD genome browser (JBrowse) to find phenotypic annotations Basic Protocol 5: Using OntoMate to find gene-disease data Basic Protocol 6: Using MOET to find gene-ontology enrichment Basic Protocol 7: Using OLGA to generate gene lists for analysis Basic Protocol 8: Using the GA tool to analyze ontology annotations for genes Basic Protocol 9: Using the RGD InterViewer tool to find protein interaction data Basic Protocol 10: Using the RGD Variant Visualizer tool to find genetic variant data Basic Protocol 11: Using the RGD Disease Portals to find disease, phenotype, and other information Basic Protocol 12: Using the RGD Phenotypes & Models Portal to find qualitative and quantitative phenotype data and other rat strain-related information Basic Protocol 13: Using the RGD Pathway Portal to find disease and phenotype data via molecular pathways.

2022 updates to the Rat Genome Database: a Findable, Accessible, Interoperable, and Reusable (FAIR) resource.

The Rat Genome Database (RGD, https://rgd.mcw.edu) has evolved from simply a resource for rat genetic markers, maps, and genes, by adding multiple genomic data types and extensive disease and phenotype annotations and developing tools to effectively mine, analyze, and visualize the available data, to empower investigators in their hypothesis-driven research. Leveraging its robust and flexible infrastructure, RGD has added data for human and eight other model organisms (mouse, 13-lined ground squirrel, chinchilla, naked mole-rat, dog, pig, African green monkey/vervet, and bonobo) besides rat to enhance its translational aspect. This article presents an overview of the database with the most recent additions to RGD's genome, variant, and quantitative phenotype data. We also briefly introduce Virtual Comparative Map (VCMap), an updated tool that explores synteny between species as an improvement to RGD's suite of tools, followed by a discussion regarding the refinements to the existing PhenoMiner tool that assists researchers in finding and comparing quantitative data across rat strains. Collectively, RGD focuses on providing a continuously improving, consistent, and high-quality data resource for researchers while advancing data reproducibility and fulfilling Findable, Accessible, Interoperable, and Reusable (FAIR) data principles.