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1.
Nat Biomed Eng ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898173

RESUMO

In pathology, the deployment of artificial intelligence (AI) in clinical settings is constrained by limitations in data collection and in model transparency and interpretability. Here we describe a digital pathology framework, nuclei.io, that incorporates active learning and human-in-the-loop real-time feedback for the rapid creation of diverse datasets and models. We validate the effectiveness of the framework via two crossover user studies that leveraged collaboration between the AI and the pathologist, including the identification of plasma cells in endometrial biopsies and the detection of colorectal cancer metastasis in lymph nodes. In both studies, nuclei.io yielded considerable diagnostic performance improvements. Collaboration between clinicians and AI will aid digital pathology by enhancing accuracies and efficiencies.

2.
JAMA Netw Open ; 7(6): e2418454, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38916895

RESUMO

This diagnostic/prognostic study assesses the ability of a large language model (LLM) to detect guardian authorship of messages originating from adolescent patient portals.


Assuntos
Tutores Legais , Portais do Paciente , Humanos , Adolescente , Masculino , Feminino , Idioma
3.
Am J Clin Pathol ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607807

RESUMO

OBJECTIVES: Identifying antibodies to red blood cell antigens is one of transfusion medicine's critical responsibilities. The International Society of Blood Transfusion recognizes 354 red blood cell antigens. Accurate identification of clinically significant alloantibodies is imperative for preventing hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. We compared the performance of the tube (polyethylene glycol-indirect antiglobulin test [PEG-IAT]) and solid-phase red cell adherence assay techniques. METHODS: We performed a retrospective study on all antibody screens performed between 2007 and 2021 at Stanford Transfusion Services. Initially, 631,535 antibody screens were performed using a solid-phase technique. Subsequent antibody identifications were performed using a combination of tube testing and solid-phase techniques. RESULTS: Antibody screening resulted in 28,316 (4.5%) positive samples. Antibody identification performed on both platforms identified 50 discordant samples. The anti-E antibody had the lowest sensitivity (98.99%) in the automated solid-phase technique, while anti-Jkb had the lowest sensitivity (98.78%) with the PEG-IAT method. CONCLUSIONS: To our knowledge, this is the first robust, 15-year study comparing methodologic sensitivity to detect clinically significant alloantibodies. The incidence of discordant results between PEG-IAT and the solid-phase technique was low. Among discordant samples, anti-Jka was commonly detected using the solid-phase method but not with the PEG-IAT. In contrast, anti-E was commonly detected by PEG-IAT but not by the solid-phase method.

4.
Arch Pathol Lab Med ; 147(3): 359-367, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35802938

RESUMO

CONTEXT.­: Stanford Pathology began stepwise subspecialty implementation of whole slide imaging (WSI) in 2018 soon after the first US Food and Drug Administration approval. In 2020, during the COVID-19 pandemic, the Centers for Medicare & Medicaid Services waived the requirement for pathologists to perform diagnostic tests in Clinical Laboratory Improvement Amendments (CLIA)-licensed facilities. This encouraged rapid implementation of WSI across all surgical pathology subspecialties. OBJECTIVE.­: To present our experience with validation and implementation of WSI at a large academic medical center encompassing a caseload of more than 50 000 cases per year. DESIGN.­: Validation was performed independently for 3 subspecialty services with a diagnostic concordance threshold above 95%. Analysis of user experience, staffing, infrastructure, and information technology was performed after department-wide expansion. RESULTS.­: Diagnostic concordance was achieved in 96% of neuropathology cases, 100% of gynecologic pathology cases, and 98% of immunohistochemistry cases. After full implementation, 8 high-capacity scanners were operational, with whole slide images generated on greater than 2000 slides per weekday, accounting for approximately 80% of histologic slides at Stanford Medicine. Multiple modifications in workflow and information technology were needed to improve performance. Within months of full implementation, most attending pathologists and trainees had adopted WSI for primary diagnosis. CONCLUSIONS.­: WSI across all surgical subspecialities is achievable at scale at an academic medical center; however, adoption required flexibility to adjust workflows and develop tailored solutions. WSI at scale supported the health and safety of medical staff while facilitating high-quality patient care and education during COVID-19 restrictions.


Assuntos
COVID-19 , Patologia Cirúrgica , Idoso , Estados Unidos , Humanos , Feminino , Patologia Cirúrgica/métodos , Interpretação de Imagem Assistida por Computador/métodos , Pandemias/prevenção & controle , Microscopia/métodos , Medicare , Teste para COVID-19
5.
BMC Bioinformatics ; 20(1): 463, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31500569

RESUMO

BACKGROUND: The Human Protein Atlas (HPA) aims to map human proteins via multiple technologies including imaging, proteomics and transcriptomics. Access of the HPA data is mainly via web-based interface allowing views of individual proteins, which may not be optimal for data analysis of a gene set, or automatic retrieval of original images. RESULTS: HPAanalyze is an R package for retrieving and performing exploratory analysis of data from HPA. HPAanalyze provides functionality for importing data tables and xml files from HPA, exporting and visualizing data, as well as downloading all staining images of interest. The package is free, open source, and available via Bioconductor and GitHub. We provide examples of the use of HPAanalyze to investigate proteins altered in the deadly brain tumor glioblastoma. For example, we confirm Epidermal Growth Factor Receptor elevation and Phosphatase and Tensin Homolog loss and suggest the importance of the GTP Cyclohydrolase I/Tetrahydrobiopterin pathway. Additionally, we provide an interactive website for non-programmers to explore and visualize data without the use of R. CONCLUSIONS: HPAanalyze integrates into the R workflow with the tidyverse framework, and it can be used in combination with Bioconductor packages for easy analysis of HPA data.


Assuntos
Análise de Dados , Armazenamento e Recuperação da Informação , Proteínas de Neoplasias/metabolismo , Software , Encéfalo/metabolismo , Encéfalo/patologia , Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Humanos
6.
PLoS One ; 13(8): e0202139, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30130366

RESUMO

Kinomics is an emerging field of science that involves the study of global kinase activity. As kinases are essential players in virtually all cellular activities, kinomic testing can directly examine protein function, distinguishing kinomics from more remote, upstream components of the central dogma, such as genomics and transcriptomics. While there exist several different approaches for kinomic research, peptide microarrays are the most widely used and involve kinase activity assessment through measurement of phosphorylation of peptide substrates on the array. Unfortunately, bioinformatic tools for analyzing kinomic data are quite limited necessitating the development of accessible open access software in order to facilitate standardization and dissemination of kinomic data for scientific use. Here, we examine and present tools for data analysis for the popular PamChip® (PamGene International) kinomic peptide microarray. As a result, we propose (1) a procedural optimization of kinetic curve data capture, (2) new methods for background normalization, (3) guidelines for the detection of outliers during parameterization, and (4) a standardized data model to store array data at various analytical points. In order to utilize the new data model, we developed a series of tools to implement the new methods and to visualize the various data models. In the interest of accessibility, we developed this new toolbox as a series of JavaScript procedures that can be utilized as either server side resources (easily packaged as web services) or as client side scripts (web applications running in the browser). The aggregation of these tools within a Kinomics Toolbox provides an extensible web based analytic platform that researchers can engage directly and web programmers can extend. As a proof of concept, we developed three analytical tools, a technical reproducibility visualizer, an ANOVA based detector of differentially phosphorylated peptides, and a heatmap display with hierarchical clustering.


Assuntos
Biologia Computacional/métodos , Fosfotransferases/metabolismo , Análise Serial de Proteínas , Proteoma , Proteômica , Software , Navegador , Algoritmos , Linhagem Celular , Ativação Enzimática , Humanos , Fosfotransferases/química , Análise Serial de Proteínas/métodos , Proteômica/métodos , Reprodutibilidade dos Testes
7.
J Pathol Inform ; 8: 41, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29114435

RESUMO

CONTEXT: Hepatitis C virus (HCV) genotyping at our institution is performed using the Versant HCV genotype 2.0 Line Probe Assay (LiPA). The last steps of this procedure are manual, laborious, and error-prone process that involves the comparison of the banding pattern on a test strip to a physical reference table. AIM: We developed a web-based HCV genotype interpretation platform that utilizes a scanned image to generate the genotypes, thus minimizing interpretation time and reducing error. SUBJECTS AND METHODS: HCV Genie 2 utilizes a database of banding patterns in conjuncture with image analysis algorithms to determine the genotype for any number of scanned LiPA strips. HCV Genie 2 is built with client-side JavaScript; allowing the program to run in the user' browser rather than on an unknown server, essentially eliminating data and patient privacy concerns. RESULTS: HCV Genie 2 was tested over 2 months and proved identical to human expert interpretation for 148 samples (>1000 bands identified). Manual intervention was required only for two faint bands and one false-positive band; this was done utilizing the built-in-user interface. Utilizing the original method, the trained laboratory technician interpretation time for 16 samples was 13.8 (±0.96) min as compared to 5.0 (±1.09) min with HCV Genie 2, a 63.8% decrease. In addition to the time savings, the new method provides an additional validation step, which decreases the potential for errors. CONCLUSIONS: Our institution has moved exclusively to utilize the new techniques and tools described here. Both experienced technicians and the molecular pathologists at our institution prefer the workflow using HCV Genie. It is easier for the technicians to prepare and document, and the pathologists are more rapidly able to review and confirm results. The use of this tool will lead to increase the quality of patient care delivered through this test methodology by decreasing the potential for error. The algorithms developed here can be ported to similar band identification platforms, most directly to other LiPAs.

8.
Bioinformatics ; 33(4): 547-548, 2017 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-27797761

RESUMO

Summary: The move of computational genomics workflows to Cloud Computing platforms is associated with a new level of integration and interoperability that challenges existing data representation formats. The Variant Calling Format (VCF) is in a particularly sensitive position in that regard, with both clinical and consumer-facing analysis tools relying on this self-contained description of genomic variation in Next Generation Sequencing (NGS) results. In this report we identify an isomorphic map between VCF and the reference Resource Description Framework. RDF is advanced by the World Wide Web Consortium (W3C) to enable representations of linked data that are both distributed and discoverable. The resulting ability to decompose VCF reports of genomic variation without loss of context addresses the need to modularize and govern NGS pipelines for Precision Medicine. Specifically, it provides the flexibility (i.e. the indexing) needed to support the wide variety of clinical scenarios and patient-facing governance where only part of the VCF data is fitting. Availability and Implementation: Software libraries with a claim to be both domain-facing and consumer-facing have to pass the test of portability across the variety of devices that those consumers in fact adopt. That is, ideally the implementation should itself take place within the space defined by web technologies. Consequently, the isomorphic mapping function was implemented in JavaScript, and was tested in a variety of environments and devices, client and server side alike. These range from web browsers in mobile phones to the most popular micro service platform, NodeJS. The code is publicly available at https://github.com/ibl/VCFr , with a live deployment at: http://ibl.github.io/VCFr/ . Contact: jonas.almeida@stonybrookmedicine.edu.


Assuntos
Variação Genética , Genoma , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNA/métodos , Software , Genômica/métodos , Humanos , Armazenamento e Recuperação da Informação , Semântica
9.
J Proteomics Bioinform ; 9(5): 151-157, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27601856

RESUMO

Kinases play a role in every cellular process involved in tumorigenesis ranging from proliferation, migration, and protein synthesis to DNA repair. While genetic sequencing has identified most kinases in the human genome, it does not describe the 'kinome' at the level of activity of kinases against their substrate targets. An attempt to address that limitation and give researchers a more direct view of cellular kinase activity is found in the PamGene PamChip® system, which records and compares the phosphorylation of 144 tyrosine or serine/threonine peptides as they are phosphorylated by cellular kinases. Accordingly, the kinetics of this time dependent kinomic signal needs to be well understood in order to transduce a parameter set into an accurate and meaningful mathematical model. Here we report the analysis and mathematical modeling of kinomic time series, which achieves a more accurate description of the accumulation of phosphorylated product than the current model, which assumes first order enzyme-substrate kinetics. Reproducibility of the proposed solution was of particular attention. Specifically, the non-linear parameterization procedure is delivered as a public open source web application where kinomic time series can be accurately decomposed into the model's two parameter values measuring phosphorylation rate and capacity. The ability to deliver model parameterization entirely as a client side web application is an important result on its own given increasing scientific preoccupation with reproducibility. There is also no need for a potentially transitory and opaque server-side component maintained by the authors, nor of exchanging potentially sensitive data as part of the model parameterization process since the code is transferred to the browser client where it can be inspected and executed.

11.
PLoS One ; 9(12): e116388, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25549342

RESUMO

PURPOSE: Researchers are currently seeking relevant lung cancer biomarkers in order to make informed decisions regarding therapeutic selection for patients in so-called "precision medicine." However, there are challenges to obtaining adequate lung cancer tissue for molecular analyses. Furthermore, current molecular testing of tumors at the genomic or transcriptomic level are very indirect measures of biological response to a drug, particularly for small molecule inhibitors that target kinases. Kinase activity profiling is therefore theorized to be more reflective of in vivo biology than many current molecular analysis techniques. As a result, this study seeks to prove the feasibility of combining a novel minimally invasive biopsy technique that expands the number of lesions amenable for biopsy with subsequent ex vivo kinase activity analysis. METHODS: Eight patients with lung lesions of varying location and size were biopsied using the novel electromagnetic navigational bronchoscopy (ENB) technique. Basal kinase activity (kinomic) profiles and ex vivo interrogation of samples in combination with tyrosine kinase inhibitors erlotinib, crizotinib, and lapatinib were performed by PamStation 12 microarray analysis. RESULTS: Kinomic profiling qualitatively identified patient specific kinase activity profiles as well as patient and drug specific changes in kinase activity profiles following exposure to inhibitor. Thus, the study has verified the feasibility of ENB as a method for obtaining tissue in adequate quantities for kinomic analysis and has demonstrated the possible use of this tissue acquisition and analysis technique as a method for future study of lung cancer biomarkers. CONCLUSIONS: We demonstrate the feasibility of using ENB-derived biopsies to perform kinase activity assessment in lung cancer patients.


Assuntos
Broncoscopia/métodos , Perfilação da Expressão Gênica/métodos , Neoplasias Pulmonares/patologia , Fosfotransferases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Idoso , Idoso de 80 Anos ou mais , Crizotinibe , Fenômenos Eletromagnéticos , Cloridrato de Erlotinib , Feminino , Perfilação da Expressão Gênica/instrumentação , Humanos , Lapatinib , Neoplasias Pulmonares/enzimologia , Masculino , Pessoa de Meia-Idade , Medicina de Precisão/métodos , Pirazóis/farmacologia , Piridinas/farmacologia , Quinazolinas/farmacologia
12.
ISME J ; 6(10): 1901-15, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22534611

RESUMO

Antarctic surface oceans are well-studied during summer when irradiance levels are high, sea ice is melting and primary productivity is at a maximum. Coincident with this timing, the bacterioplankton respond with significant increases in secondary productivity. Little is known about bacterioplankton in winter when darkness and sea-ice cover inhibit photoautotrophic primary production. We report here an environmental genomic and small subunit ribosomal RNA (SSU rRNA) analysis of winter and summer Antarctic Peninsula coastal seawater bacterioplankton. Intense inter-seasonal differences were reflected through shifts in community composition and functional capacities encoded in winter and summer environmental genomes with significantly higher phylogenetic and functional diversity in winter. In general, inferred metabolisms of summer bacterioplankton were characterized by chemoheterotrophy, photoheterotrophy and aerobic anoxygenic photosynthesis while the winter community included the capacity for bacterial and archaeal chemolithoautotrophy. Chemolithoautotrophic pathways were dominant in winter and were similar to those recently reported in global 'dark ocean' mesopelagic waters. If chemolithoautotrophy is widespread in the Southern Ocean in winter, this process may be a previously unaccounted carbon sink and may help account for the unexplained anomalies in surface inorganic nitrogen content.


Assuntos
Archaea/classificação , Bactérias/classificação , Metagenômica , Estações do Ano , Água do Mar/microbiologia , Regiões Antárticas , Archaea/genética , Processos Autotróficos , Bactérias/genética , DNA Arqueal/genética , DNA Bacteriano/genética , Biblioteca Gênica , Processos Heterotróficos , Filogenia , Plâncton/classificação , Plâncton/genética , RNA Ribossômico/genética , Análise de Sequência de DNA
13.
ISME J ; 6(1): 71-80, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21697958

RESUMO

Marine microorganisms thrive under low levels of nitrogen (N). N cost minimization is a major selective pressure imprinted on open-ocean microorganism genomes. Here we show that amino-acid sequences from the open ocean are reduced in N, but increased in average mass compared with coastal-ocean microorganisms. Nutrient limitation exerts significant pressure on organisms supporting the trade-off between N cost minimization and increased average mass of amino acids that is a function of increased A+T codon usage. N cost minimization, especially of highly expressed proteins, reduces the total cellular N budget by 2.7-10%; this minimization in combination with reduction in genome size and cell size is an evolutionary adaptation to nutrient limitation. The biogeochemical and evolutionary precedent for these findings suggests that N limitation is a stronger selective force in the ocean than biosynthetic costs and is an important evolutionary strategy in resource-limited ecosystems.


Assuntos
Bactérias/metabolismo , Nitrogênio/metabolismo , Água do Mar/microbiologia , Aminoácidos/metabolismo , Bactérias/genética , Códon , Metabolismo Energético , Tamanho do Genoma , Oceanos e Mares , Proteoma/metabolismo
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