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The Long-read RNA-Seq Genome Annotation Assessment Project Consortium was formed to evaluate the effectiveness of long-read approaches for transcriptome analysis. Using different protocols and sequencing platforms, the consortium generated over 427 million long-read sequences from complementary DNA and direct RNA datasets, encompassing human, mouse and manatee species. Developers utilized these data to address challenges in transcript isoform detection, quantification and de novo transcript detection. The study revealed that libraries with longer, more accurate sequences produce more accurate transcripts than those with increased read depth, whereas greater read depth improved quantification accuracy. In well-annotated genomes, tools based on reference sequences demonstrated the best performance. Incorporating additional orthogonal data and replicate samples is advised when aiming to detect rare and novel transcripts or using reference-free approaches. This collaborative study offers a benchmark for current practices and provides direction for future method development in transcriptome analysis.
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Perfilação da Expressão Gênica , RNA-Seq , Humanos , Animais , Camundongos , RNA-Seq/métodos , Perfilação da Expressão Gênica/métodos , Transcriptoma , Análise de Sequência de RNA/métodos , Anotação de Sequência Molecular/métodosRESUMO
We have made the compound 2O-BaPtO3 by high-pressure, high-temperature synthesis, determined its structure, and tested its catalytic activity. Compounds of the same stoichiometry have been reported and tentatively identified as hexagonal perovskites, and although no structural model was ever established, 2O-BaPtO3 is clearly different and, to the best of our knowledge, unique. It features continuous chains of face-sharing PtO6 octahedra, like the well-known 2H hexagonal perovskite type, but with a staggered offset between the chains that breaks hexagonal symmetry and disrupts the close-packed array of A = Ba and X = O that is a defining characteristic of ABX3 perovskites. We investigated this structure and its stability vs the conventional 2H form using X-ray and neutron diffraction, X-ray absorption spectroscopy, and ab initio calculations. Catalytic testing of 2O-BaPtO3 showed that it is active for hydrogen evolution.
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Ensembl (https://www.ensembl.org) is a freely available genomic resource that has produced high-quality annotations, tools, and services for vertebrates and model organisms for more than two decades. In recent years, there has been a dramatic shift in the genomic landscape, with a large increase in the number and phylogenetic breadth of high-quality reference genomes, alongside major advances in the pan-genome representations of higher species. In order to support these efforts and accelerate downstream research, Ensembl continues to focus on scaling for the rapid annotation of new genome assemblies, developing new methods for comparative analysis, and expanding the depth and quality of our genome annotations. This year we have continued our expansion to support global biodiversity research, doubling the number of annotated genomes we support on our Rapid Release site to over 1700, driven by our close collaboration with biodiversity projects such as Darwin Tree of Life. We have also strengthened support for key agricultural species, including the first regulatory builds for farmed animals, and have updated key tools and resources that support the global scientific community, notably the Ensembl Variant Effect Predictor. Ensembl data, software, and tools are freely available.
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Bases de Dados Genéticas , Genômica , Animais , Genoma , Anotação de Sequência Molecular , Filogenia , Software , HumanosRESUMO
OBJECTIVE: Poor interdisciplinary care team communication has been associated with increased mortality. The study aimed to define conditions for effective interdisciplinary care team communication. DESIGN: An observational cross-sectional qualitative study. SETTING: A surgical intensive care unit in a large, urban, academic referral medical centre. PARTICIPANTS: A total 6 interviews and 10 focus groups from February to June 2021 (N=33) were performed. Interdisciplinary clinicians who cared for critically ill patients were interviewed. Participants included intensivist, transplant, colorectal, vascular, surgical oncology, trauma faculty surgeons (n=10); emergency medicine, surgery, gynaecology, radiology physicians-in-training (n=6), advanced practice providers (n=5), nurses (n=7), fellows (n=1) and subspecialist clinicians such as respiratory therapists, pharmacists and dieticians (n=4). Audiorecorded content of interviews and focus groups were deidentified and transcribed verbatim. The study team iteratively generated the codebook. All transcripts were independently coded by two team members. PRIMARY OUTCOME: Conditions for effective interdisciplinary care team communication. RESULTS: We identified five themes relating to conditions for effective interdisciplinary care team communication in our surgical intensive care unit setting: role definition, formal processes, informal communication pathways, hierarchical influences and psychological safety. Participants reported that clear role definition and standardised formal communication processes empowered clinicians to engage in discussions that mitigated hierarchy and facilitated psychological safety. CONCLUSIONS: Standardising communication and creating defined roles in formal processes can promote effective interdisciplinary care team communication by fostering psychological safety.
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Comunicação Interdisciplinar , Equipe de Assistência ao Paciente , Humanos , Estudos Transversais , Pesquisa Qualitativa , Unidades de Terapia Intensiva , Comunicação , Cuidados CríticosRESUMO
As digital mental health interventions (DMHIs) proliferate, there is a growing need to understand the complexities of moving these tools from concept and design to service-ready products. We highlight five case studies from a center that specializes in the design and evaluation of digital mental health interventions to illustrate pragmatic approaches to the development of digital mental health interventions, and to make transparent some of the key decision points researchers encounter along the design-to-product pipeline. Case studies cover different key points in the design process and focus on partnership building, understanding the problem or opportunity, prototyping the product or service, and testing the product or service. We illustrate lessons learned and offer a series of questions researchers can use to navigate key decision points in the digital mental health intervention (DMHI) development process.
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The Long-read RNA-Seq Genome Annotation Assessment Project (LRGASP) Consortium was formed to evaluate the effectiveness of long-read approaches for transcriptome analysis. The consortium generated over 427 million long-read sequences from cDNA and direct RNA datasets, encompassing human, mouse, and manatee species, using different protocols and sequencing platforms. These data were utilized by developers to address challenges in transcript isoform detection and quantification, as well as de novo transcript isoform identification. The study revealed that libraries with longer, more accurate sequences produce more accurate transcripts than those with increased read depth, whereas greater read depth improved quantification accuracy. In well-annotated genomes, tools based on reference sequences demonstrated the best performance. When aiming to detect rare and novel transcripts or when using reference-free approaches, incorporating additional orthogonal data and replicate samples are advised. This collaborative study offers a benchmark for current practices and provides direction for future method development in transcriptome analysis.
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BACKGROUND: Better information sharing in intensive care units has been associated with lower risk-adjusted mortality. This study explored how team characteristics and leadership are associated with information sharing in 4 intensive care units in a single large urban, academic medical center. METHODS: A qualitative study was conducted to understand how team characteristics and leadership are associated with information sharing. Qualitative data were conducted through ethnographic observations. One postdoctoral research fellow and one PhD qualitative researcher conducted nonparticipant observations of a Medical, Surgical, Neurological, and Cardiothoracic intensive care unit morning and afternoon rounds, as well as nurse and resident handoffs from May to September 2021. Field notes of observations were thematically analyzed using deductive reasoning anchored to the Edmondson Team Learning Model. This study included nurses, physicians (ie, intensivists, surgeons, fellows, and residents), medical students, pharmacists, respiratory therapists, dieticians, physical therapists, physician assistants, and nurse practitioners. RESULTS: We conducted 50 person-hours of observations involving 148 providers. Three themes emerged from the qualitative analysis: (1) team leaders used variable leadership techniques to involve team members in discussions for information sharing related to patient care, (2) predefined tasks for team members allowed them to prepare for effective information sharing during intensive care unit rounds, and (3) a psychologically safe environment allowed team members to participate in discussions for information sharing related to patient care. CONCLUSION: Inclusive team leadership is foundational in creating a psychologically safe environment for effective information sharing.
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Liderança , Cirurgiões , Humanos , Equipe de Assistência ao Paciente , Unidades de Terapia Intensiva , Pesquisa Qualitativa , Disseminação de InformaçãoRESUMO
Balance recovery after tripping often requires an active adaptation of foot placement. Thus far, few attempts have been made to actively assist forward foot placement for balance recovery employing wearable devices. This study aims to explore the possibilities of active forward foot placement through two paradigms of actuation: assistive moments exerted with the reaction moments either internal or external to the human body, namely 'joint' moments and 'free' moments, respectively. Both paradigms can be applied to manipulate the motion of segments of the body (e.g., the shank or thigh), but joint actuators also exert opposing reaction moments on neighbouring body segments, altering posture and potentially inhibiting tripping recovery. We therefore hypothesised that a free moment paradigm is more effective in assisting balance recovery following tripping. The simulation software SCONE was used to simulate gait and tripping over various ground-fixed obstacles during the early swing phase. To aid forward foot placement, joint moments and free moments were applied either on the thigh to augment hip flexion or on the shank to augment knee extension. Two realizations of joint moments on the hip were simulated, with the reaction moment applied to either the pelvis or the contralateral thigh. The simulation results show that assisting hip flexion with either actuation paradigm on the thigh can result in full recovery of gait with a margin of stability and leg kinematics closely matching the unperturbed case. However, when assisting knee extension with moments on the shank, free moment effectively assist balance but joint moments with the reaction moment on the thigh do not. For joint moments assisting hip flexion, placement of the reaction moment on the contralateral thigh was more effective in achieving the desired limb dynamics than placing the reaction on the pelvis. Poor choice of placement of reaction moments may therefore have detrimental consequences for balance recovery, and removing them entirely (i.e., free moment) could be a more effective and reliable alternative. These results challenge conventional assumptions and may inform the design and development of a new generation of minimalistic wearable devices to promote balance during gait.
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Robótica , Humanos , Extremidade Inferior , Perna (Membro) , Articulação do Joelho , Marcha , Fenômenos BiomecânicosRESUMO
OBJECTIVES: Patient and provider-facing screening tools for social determinants of health have been explored in a variety of contexts; however, effective screening and resource referral remain challenging, and less is known about how patients perceive chatbots as potential social needs screening tools. We investigated patient perceptions of a chatbot for social needs screening using three implementation outcome measures: acceptability, feasibility, and appropriateness. METHODS: We implemented a chatbot for social needs screening at one large public hospital emergency department (ED) and used concurrent triangulation to assess perceptions of the chatbot use for screening. A total of 350 ED visitors completed the social needs screening and rated the chatbot on implementation outcome measures, and 22 participants engaged in follow-up phone interviews. RESULTS: The screened participants ranged in age from 18 to 90 years old and were diverse in race/ethnicity, education, and insurance status. Participants (n = 350) rated the chatbot as an acceptable, feasible, and appropriate way of screening. Through interviews (n = 22), participants explained that the chatbot was a responsive, private, easy to use, efficient, and comfortable channel to report social needs in the ED, but wanted more information on data use and more support in accessing resources. CONCLUSION: In this study, we deployed a chatbot for social needs screening in a real-world context and found patients perceived the chatbot to be an acceptable, feasible, and appropriate modality for social needs screening. Findings suggest that chatbots are a promising modality for social needs screening and can successfully engage a large, diverse patient population in the ED. This is significant, as it suggests that chatbots could facilitate a screening process that ultimately connects patients to care for social needs, improving health and well-being for members of vulnerable patient populations.
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Serviço Hospitalar de Emergência , Encaminhamento e Consulta , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Projetos de Pesquisa , SoftwareRESUMO
BACKGROUND: Annual cognitive screening in adults aged >65 years can improve early detection of cognitive impairment, yet less than half of all cases are identified in primary care. Time constraints in primary care settings present a major barrier to routine screening. A remote cognitive screener completed on a patient's own smartphone before a visit has the potential to save primary care clinics time, encourage broader screening practices, and increase early detection of cognitive decline. OBJECTIVE: We described the iterative design and proposed the implementation of a remote cognitive screening app, MyCog Mobile, to be completed on a patient's smartphone before an annual wellness visit. The research questions were as follows: What would motivate primary care clinicians and clinic administrators to implement a remote cognitive screening process? How might we design a remote cognitive screener to fit well with existing primary care workflows? What would motivate an older adult patient to complete a cognitive screener on a smartphone before a primary care visit? How might we optimize the user experience of completing a remote cognitive screener on a smartphone for older adults? METHODS: To address research questions 1 and 2, we conducted individual interviews with clinicians (n=5) and clinic administrators (n=3). We also collaborated with clinic administrators to create user journey maps of their existing and proposed MyCog Mobile workflows. To address research questions 3 and 4, we conducted individual semistructured interviews with cognitively healthy older adults (n=5) and solicited feedback from a community stakeholder panel (n=11). We also tested and refined high-fidelity prototypes of the MyCog Mobile app with the older adult interview participants, who rated the usability on the Simplified System Usability Scale and After-Scenario Questionnaire. RESULTS: Clinicians and clinic administrators were motivated to adopt a remote cognitive screening process if it saved time in their workflows. Findings from interviews and user journey mapping informed the proposed implementation and core functionality of MyCog Mobile. Older adult participants were motivated to complete cognitive screeners to ensure that they were cognitively healthy and saw additional benefits to remote screening, such as saving time during their visit and privacy. Older adults also identified potential challenges to remote smartphone screening, which informed the user experience design of the MyCog Mobile app. The average rating across prototype versions was 91 (SD 5.18) on the Simplified System Usability Scale and 6.13 (SD 8.40) on the After-Scenario Questionnaire, indicating above-average usability. CONCLUSIONS: Through an iterative, human-centered design process, we developed a viable remote cognitive screening app and proposed an implementation strategy for primary care settings that was optimized for multiple stakeholders. The next steps include validating the cognitive screener in clinical and healthy populations and piloting the finalized app in a community primary care clinic.
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Ensembl (https://www.ensembl.org) has produced high-quality genomic resources for vertebrates and model organisms for more than twenty years. During that time, our resources, services and tools have continually evolved in line with both the publicly available genome data and the downstream research and applications that utilise the Ensembl platform. In recent years we have witnessed a dramatic shift in the genomic landscape. There has been a large increase in the number of high-quality reference genomes through global biodiversity initiatives. In parallel, there have been major advances towards pangenome representations of higher species, where many alternative genome assemblies representing different breeds, cultivars, strains and haplotypes are now available. In order to support these efforts and accelerate downstream research, it is our goal at Ensembl to create high-quality annotations, tools and services for species across the tree of life. Here, we report our resources for popular reference genomes, the dramatic growth of our annotations (including haplotypes from the first human pangenome graphs), updates to the Ensembl Variant Effect Predictor (VEP), interactive protein structure predictions from AlphaFold DB, and the beta release of our new website.
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Bases de Dados Genéticas , Software , Animais , Humanos , Anotação de Sequência Molecular , Genômica , GenomaRESUMO
GENCODE produces high quality gene and transcript annotation for the human and mouse genomes. All GENCODE annotation is supported by experimental data and serves as a reference for genome biology and clinical genomics. The GENCODE consortium generates targeted experimental data, develops bioinformatic tools and carries out analyses that, along with externally produced data and methods, support the identification and annotation of transcript structures and the determination of their function. Here, we present an update on the annotation of human and mouse genes, including developments in the tools, data, analyses and major collaborations which underpin this progress. For example, we report the creation of a set of non-canonical ORFs identified in GENCODE transcripts, the LRGASP collaboration to assess the use of long transcriptomic data to build transcript models, the progress in collaborations with RefSeq and UniProt to increase convergence in the annotation of human and mouse protein-coding genes, the propagation of GENCODE across the human pan-genome and the development of new tools to support annotation of regulatory features by GENCODE. Our annotation is accessible via Ensembl, the UCSC Genome Browser and https://www.gencodegenes.org.
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Biologia Computacional , Genoma Humano , Humanos , Animais , Camundongos , Anotação de Sequência Molecular , Biologia Computacional/métodos , Genoma Humano/genética , Transcriptoma/genética , Perfilação da Expressão Gênica , Bases de Dados GenéticasRESUMO
Background: There is increasing emphasis on resident involvement in quality improvement (QI) efforts, yet resident engagement in QI has remained low for many reasons. Although QI methods are classically applied to clinical processes, there are many opportunities to incorporate QI principles into curricular design and implementation. Objective: Demonstrate the utility of QI methods when applied to curricular design and the implementation of a novel point-of-care ultrasound portfolio development and quality assurance program at a large internal medicine residency program. Methods: We applied foundational QI methods, including process mapping, plan-do-study-act (PDSA) cycles, time-trap identification, run-chart analysis, and qualitative interviews throughout the curricular design and implementation phases to rapidly identify areas for improvement and perform timely tests of change. Results: Fifty-one interns participated in the curriculum, submitting 731 images in the first trimester. Process mapping and submission review revealed that 29% of images were saved to the incorrect digital archive. Resident-reviewer interpretation concordance was present in 80.7% of submissions. In 95.2% of completed quality assurance cards, the same information was provided in the commentary feedback and the evaluator's checklists, representing a time trap. Interventions included restricting access to image archives and removing redundant fields from quality assurance cards. The time to feedback fell from 69.5 to 6.5 days, demonstrating nonrandom variation via run-chart analysis. Conclusion: This pilot study demonstrates the successful application of QI methods to a novel point-of-care ultrasound curriculum. The systematic use of these methodologies in curricular design and implementation allows expeditious curricular improvement. Emphasizing the relevance of QI methods to subject matter beyond clinical processes may increase resident engagement in QI efforts.
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INTRODUCTION: Telemetry is ubiquitous in many hospitals despite widely acknowledged limitations, waste, and potential harm associated with inappropriate use. To curb overuse, guidelines such as the 2017 American Heart Association/American College of Cardiology (AHA/ACC) continuous telemetry monitoring practice standards have outlined appropriate telemetry use standards. This study aimed to perform two "plan-do-study-act" (PDSA) cycles and assess whether a nursing (RN)-driven checklist addressing appropriate telemetry use, combined with just-in-time education delivered via an electronic health record (EHR) order set modification, was efficacious in reducing inappropriate telemetry use within a level 1a Veterans Health Administration hospital. METHODS: This is a quality improvement intervention study that took place between March 2019 and August 2020. Three cohorts were sequentially studied: a control cohort without any intervention (n = 100), a cohort with only the RN-driven checklist (n = 100), and a cohort with both the RN-driven checklist and an EHR order set modification that provided just-in-time education about telemetry indications (n = 100). Telemetry records were reviewed by a physician to determine indication, duration for each telemetry order, and appropriateness. An order was deemed "appropriate" if it met AHA/ACC classification grade I (telemetry recommended) or IIa/b (telemetry may be considered) and "inappropriate" if it fell under class III (telemetry not recommended). Data were compared between the control cohort and the two intervention cohorts, as well as between intervention cohorts, using Pearson chi-square analysis. A p-value < 0.05 was considered statistically significant. RESULTS: Within the control group, 37% of telemetry orders were deemed inappropriate. After implementation of the RN checklist, a non-statistically significant lower proportion (26%) of orders was deemed inappropriate (p = 0.09). Implementation of the RN checklist, along with the EHR order set, was associated with a significantly lower proportion of inappropriate orders (17%) in comparison to the control cohort (p = 0.001) but not in comparison to the RN checklist cohort (p = 0.12). There was no significant difference in the duration of telemetry use across cohorts. CONCLUSIONS: An RN-driven checklist and EHR telemetry order set modification were associated with a decrease in inappropriate telemetry use from 37% to 17%. By prompting the review of telemetry orders via a daily nursing checklist reviewed during bedside interdisciplinary rounds, clinicians received reinforcement regarding appropriate telemetry indications. This education was strengthened by the just-in-time training provided via the EHR order set.
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Evolution by natural selection is an explicitly genetic theory. Darwin recognized that a working theory of inheritance was central to his theory and spent much of his scientific life seeking one. The seeds of his attempt to fill this gap, his "provisional hypothesis" of pangenesis, appear in his notebooks when he was first formulating his evolutionary ideas. Darwin, in short, desperately needed Mendel. In this paper, we set Mendel's work in the context of experimental biology and animal/plant breeding of the period and review both the well-known story of possible contact between Mendel and Darwin and the actual contact between their ideas after their deaths. Mendel's contributions to evolutionary biology were fortuitous. Regardless, it is Mendel's work that completed Darwin's theory. The modern theory based on the marriage between Mendel's and Darwin's ideas as forged most comprehensively by R. A. Fisher is both Darwin's achievement and Mendel's.
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Evolução Biológica , Cruzamento , Genética , Seleção Genética , Animais , Cruzamento/história , Genética/história , História do Século XIX , Padrões de Herança , Plantas/genética , Probabilidade , SementesRESUMO
INTRODUCTION: Over the last decade, there has been a 32% decrease in independent plastic surgery fellowships. The growing prevalence of 6-year integrated plastic surgery residencies, duty hour restrictions, and new subspecialty training fellowships for general surgeons have changed the training experience of plastic surgery fellows. METHODS: A retrospective review of the Accreditation Council for Graduate Medical Education (ACGME) case logs for graduating fellows of independent plastic surgery fellowships in the United States was conducted from 2011 to 2019. A linear regression analysis was conducted for each case log code and category, and a 95% level of confidence was assumed (α = 0.05). RESULTS: In 2011, 141 residents from 69 programs graduated with an average of 1469.7 cases. In 2019, 84 residents from 47 programs graduated with an average of 1952 cases. Index procedures significantly increased overall during the 9 y (P < 0.001). Categorical cases increased in esthetics (P < 0.001), including facelift, browlift, blepharoplasty, and more. Categorical cases increased in reconstructive surgery (P < 0.001), including treatment of deformities of the skin, lower extremities, and trunk, nerve decompression, and hand reconstruction. In breast procedures, an increase was seen in the reduction of mammoplasty, reconstruction, and treatment of other breast deformities. In head and neck procedures, an increase was seen in resection of head and neck neoplasms and secondary cleft lip repair. Decreases in procedural numbers were seen in primary cleft lip repair and hand reconstruction by primary closure. CONCLUSIONS: Despite a 32% decline in the number of independent plastic surgery fellowships over the last 9 y, plastic surgery fellows are obtaining significantly more surgical experience, both in esthetic and reconstructive surgery.
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Fenda Labial , Cirurgia Geral , Internato e Residência , Mamoplastia , Cirurgia Plástica , Acreditação , Competência Clínica , Educação de Pós-Graduação em Medicina/métodos , Bolsas de Estudo , Cirurgia Geral/educação , Humanos , Cirurgia Plástica/educação , Estados UnidosRESUMO
The initial melts erupted by a Hawaiian volcano have a range of alkalic compositions but are rarely observed as they are covered by enormous volumes of shield stage tholeiites. A remarkable record of the early evolution of Hawaiian volcanoes, however, is preserved by a volcanic sandstone dredged from the submarine flank of Kilauea, which contains a suite of petrogenetically related pre-shield basanite to nephelinite glasses. Here we show that the systematic variation in the rare earth element (REE) patterns of these samples requires the fractional crystallisation of garnet. A fractionating assemblage of Ca-rich garnet (32%), omphacitic clinopyroxene (63%), and minor phlogopite can explain the variation in the major and trace element contents of the suite. The results suggest fractional crystallisation of eclogite from a primitive Hawaiian melt near the base of the lithosphere (>90 km) and that a deep magma chamber is the first stage in the development of a Hawaiian volcano.
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Comprehensive genome annotation is essential to understand the impact of clinically relevant variants. However, the absence of a standard for clinical reporting and browser display complicates the process of consistent interpretation and reporting. To address these challenges, Ensembl/GENCODE1 and RefSeq2 launched a joint initiative, the Matched Annotation from NCBI and EMBL-EBI (MANE) collaboration, to converge on human gene and transcript annotation and to jointly define a high-value set of transcripts and corresponding proteins. Here, we describe the MANE transcript sets for use as universal standards for variant reporting and browser display. The MANE Select set identifies a representative transcript for each human protein-coding gene, whereas the MANE Plus Clinical set provides additional transcripts at loci where the Select transcripts alone are not sufficient to report all currently known clinical variants. Each MANE transcript represents an exact match between the exonic sequences of an Ensembl/GENCODE transcript and its counterpart in RefSeq such that the identifiers can be used synonymously. We have now released MANE Select transcripts for 97% of human protein-coding genes, including all American College of Medical Genetics and Genomics Secondary Findings list v3.0 (ref. 3) genes. MANE transcripts are accessible from major genome browsers and key resources. Widespread adoption of these transcript sets will increase the consistency of reporting, facilitate the exchange of data regardless of the annotation source and help to streamline clinical interpretation.