English
norskBlar i forfatter "Butler, Lynn"
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An artificial neural network approach integrating plasma proteomics and genetic data identifies PLXNA4 as a new susceptibility locus for pulmonary embolism
(Journal article; Tidsskriftartikkel; Peer reviewed, 2021-07-07)Venous thromboembolism is the third common cardiovascular disease and is composed of two entities, deep vein thrombosis (DVT) and its potential fatal form, pulmonary embolism (PE). While PE is observed in~ 40% of patients with documented DVT, there is limited biomarkers that can help identifying patients at high PE risk. To fll this need, we implemented a two hidden-layers artifcial neural ... -
Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism
(Journal article; Tidsskriftartikkel; Peer reviewed, 2023-06-07)Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. Here we show, using proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, how Complement ... -
A human adipose tissue cell-type transcriptome atlas
(Journal article; Tidsskriftartikkel; Peer reviewed, 2022-07-12)The importance of defining cell-type-specific genes is well acknowledged. Technological advances facilitate high-resolution sequencing of single cells, but practical challenges remain. Adipose tissue is composed primarily of adipocytes, large buoyant cells requiring extensive, artefact-generating processing for separation and analysis. Thus, adipocyte data are frequently absent from single-cell ... -
Identification of Endothelial Proteins in Plasma Associated With Cardiovascular Risk Factors
(Journal article; Tidsskriftartikkel; Peer reviewed, 2021-10-28)<b>Objective:</b> Endothelial cell (EC) dysfunction is a well-established response to cardiovascular disease risk factors, such as smoking and obesity. Risk factor exposure can modify EC signaling and behavior, leading to arterial and venous disease development. Here, we aimed to identify biomarker panels for the assessment of EC dysfunction, which could be useful for risk stratification or to monitor ... -
Identification of the factor XII contact activation site enables sensitive coagulation diagnostics
(Journal article; Tidsskriftartikkel; Peer reviewed, 2021-09-22)Contact activation refers to the process of surface-induced activation of factor XII (FXII), which initiates blood coagulation and is captured by the activated partial thromboplastin time (aPTT) assay. Here, we show the mechanism and diagnostic implications of FXII contact activation. Screening of recombinant FXII mutants identified a continuous stretch of residues Gln317–Ser339 that was essential ... -
Intrinsic coagulation pathway-mediated thrombin generation in mouse whole blood
(Journal article; Tidsskriftartikkel; Peer reviewed, 2022-11-28)Calibrated Automated Thrombography (CAT) is a versatile and sensitive method for analyzing coagulation reactions culminating in thrombin generation (TG). Here, we present a CAT method for analyzing TG in murine whole blood by adapting the CAT assay used for measuring TG in human plasma. The diagnostically used artificial and physiologic factor XII (FXII) contact activators kaolin, ellagic acid ... -
Proteomics in thrombosis research
(Journal article; Tidsskriftartikkel; Peer reviewed, 2022-04-25)A State of the Art lecture titled “Proteomics in Thrombosis Research” was presented at the ISTH Congress in 2021. In clinical practice, there is a need for improved plasma biomarker-based tools for diagnosis and risk prediction of venous thromboembolism (VTE). Analysis of blood, to identify plasma proteins with potential utility for such tools, could enable an individualized approach to treatment ... -
A single-cell type transcriptomics map of human tissues
(Journal article; Tidsskriftartikkel; Peer reviewed, 2021-07-28)Advances in molecular profiling have opened up the possibility to map the expression of genes in cells, tissues, and organs in the human body. Here, we combined single-cell transcriptomics analysis with spatial antibodybased protein profiling to create a high-resolution single–cell type map of human tissues. An open access atlas has been launched to allow researchers to explore the expression of ... -
A Systems-Based Map of Human Brain Cell-Type Enriched Genes and Malignancy-Associated Endothelial Changes
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-11-05)Changes in the endothelium of the cerebral vasculature can contribute to inflammatory, thrombotic, and malignant disorders. The importance of defining cell-type-specific genes and their modification in disease is increasingly recognized. Here, we develop a bioinformatics-based approach to identify normal brain cell-enriched genes, using bulk RNA sequencing (RNA-seq) data from 238 normal human cortex ... -
Targeting NETs using dual-active DNase1 variants
(Journal article; Tidsskriftartikkel; Peer reviewed, 2023-05-23)Background: Neutrophil Extracellular Traps (NETs) are key mediators of immunothrombotic mechanisms and defective clearance of NETs from the circulation underlies an array of thrombotic, inflammatory, infectious, and autoimmune diseases. Efficient NET degradation depends on the combined activity of two distinct DNases, DNase1 and DNase1-like 3 (DNase1L3) that preferentially digest double-stranded DNA ... -
Xenotropic and polytropic retrovirus receptor 1 regulates procoagulant platelet polyphosphate
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-09-15)Polyphosphate is a procoagulant inorganic polymer of linear-linked orthophosphate residues. Multiple investigations have established the importance of platelet polyphosphate in blood coagulation; however, the mechanistic details of polyphosphate homeostasis in mammalian species remain largely undefined. In this study, xenotropic and polytropic retrovirus receptor 1 (XPR1) regulated polyphosphate in ...
