A5086012146- Rheumatoid Arthritis Research and Therapies
- Computational Drug Discovery Methods
- Inflammatory Bowel Disease
- Complement system in diseases
- Chronic Lymphocytic Leukemia Research
- Systemic Lupus Erythematosus Research
- Pharmacovigilance and Adverse Drug Reactions
- Hepatitis C virus research
- Bioinformatics and Genomic Networks
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Ferroptosis and cancer prognosis
- Protein Structure and Dynamics
- Cytokine Signaling Pathways and Interactions
- vaccines and immunoinformatics approaches
- Molecular spectroscopy and chirality
- Biosimilars and Bioanalytical Methods
- Receptor Mechanisms and Signaling
- Cell Image Analysis Techniques
- Autoimmune and Inflammatory Disorders Research
- Microbial Natural Products and Biosynthesis
- Advanced Mathematical Modeling in Engineering
- T-cell and B-cell Immunology
- Gene expression and cancer classification
- Nonlinear Partial Differential Equations
Pfizer (United States)
2016-2023
Karolinska Institutet
2020-2022
Karolinska University Hospital
2022
Medical University of Lodz
2022
Technical University of Denmark
2020
Avidea Technologies (United States)
2020
Novartis (United States)
2017
Poznań University of Technology
2016
Corbus Pharmaceuticals (United States)
2015
Novartis (Switzerland)
2014
Therapeutic modulation of the complement system has become increasingly important in line with growing recognition role numerous diseases. Compstatin, a peptidic inhibitor that acts at central level cascade, is currently clinical evaluation but routes to improve its efficacy have not yet been fully explored. Here, we report improvements both inhibitory potency and pharmacokinetic parameters compstatin broaden applications. Selective modification N-terminus non-proteinogenic amino acids...
Molecular profiling efforts aim at characterizing the biological actions of small molecules by screening them in hundreds different biochemical and/or cell-based assays. Together, these assays yield a rich data landscape target-based and phenotypic effects tested compounds. However, submitting an entire compound library to molecular panel can easily become cost-prohibitive. Here, we make use historical create comprehensive bioactivity profiles for more than 300 000 molecules. These profiles,...
Approximately 30-40% of rheumatoid arthritis (RA) patients who are initially started on low-dose methotrexate (MTX) will not benefit from the treatment. To date, no reliable biomarkers MTX inefficacy in RA have been identified. The aim this study was to analyze whole blood samples at 2 time points (pretreatment and 4 weeks following initiation MTX), identify gene expression response.RA were about commence treatment with selected Rheumatoid Arthritis Medication Study. Using European League...
Abstract Background The ability to confidently predict health outcomes from gene expression would catalyze a revolution in molecular diagnostics. Yet, the goal of developing actionable, robust, and reproducible predictive signatures phenotypes such as clinical outcome has not been attained almost any disease area. Here, we report comprehensive analysis spanning prediction tasks ulcerative colitis, atopic dermatitis, diabetes, many cancer subtypes for total 24 binary multiclass problems 26...
Advances in immunotherapy by blocking TNF have remarkably improved treatment outcomes for Rheumatoid arthritis (RA) patients. Although specifically targets TNF, the downstream mechanisms of immune suppression are not completely understood. The aim this study was to detect biomarkers and expression signatures response inhibition.Peripheral blood mononuclear cells (PBMCs) from 39 female patients were collected before anti-TNF initiation (day 0) after 3 months. cohort included previously...
The Food and Drug Administration Adverse Event Reporting System (FAERS) remains the primary source for post-marketing pharmacovigilance. system is largely un-curated, unstandardized, lacks a method linking drugs to chemical structures of their active ingredients, increasing noise artefactual trends. To address these problems, we mapped ingredients used natural language processing classify correlate drug events. Our analysis exposed key idiosyncrasies in FAERS, example reports thalidomide...
Abstract Methotrexate (MTX) is a common first-line treatment for new-onset rheumatoid arthritis (RA). However, MTX ineffective 30–40% of patients and there no way to know which might benefit. Here, we built statistical models based on serum lipid levels measured at two time-points (pre-treatment following 4 weeks on-drug) investigate if response (by 6 months) could be predicted. Patients about commence the first time were selected from Rheumatoid Arthritis Medication Study (RAMS)....
Background Methotrexate (MTX) is the first line treatment for rheumatoid arthritis (RA), but failure of satisfying response occurs in a significant proportion patients. Here we present longitudinal multi-omics study aimed at detecting molecular and cellular processes peripheral blood associated with successful methotrexate arthritis. Methods Eighty newly diagnosed patients RA underwent clinical assessment donated before initiation MTX, 3 months into treatment. Flow cytometry was used to...
Deep learning-based denoising and upscaling techniques have emerged to enhance framerates for real-time rendering. A single neural network joint offers the advantage of sharing parameters in feature space, enabling efficient prediction filter weights both. However, it is still ongoing research devise an extraction that uses different characteristics inputs two combined problems. We propose a multi-branch, multi-scale upscaling. The proposed multi-branch U-Net architecture lightweight...
To survive and replicate within the human host, malaria parasites must invade erythrocytes. Invasion can be mediated by P. falciparum reticulocyte-binding homologue protein 4 (PfRh4) on merozoite surface interacting with complement receptor type 1 (CR1, CD35) erythrocyte membrane. The PfRh4 attachment site lies three N-terminal control modules (CCPs 1-3) of CR1, which intriguingly also accommodate binding regulatory sites for key activation-specific proteolytic products, C3b C4b. One these...
Gene-based supervised machine learning classification models have been widely used to differentiate disease states, predict progression and determine effective treatment options. However, many of these classifiers are sensitive noise frequently do not replicate in external validation sets. For complex, heterogeneous diseases, further limited by being unable capture varying combinations genes that lead the same phenotype. Pathway-based can overcome challenges using robust, aggregate features...
Objective The objectives of this study were to assess the 1‐year persistence methotrexate (MTX) initiated as first ever conventional synthetic disease‐modifying antirheumatic drug in new‐onset rheumatoid arthritis (RA) and investigate marginal gains robustness results by increasing number nature covariates using data‐driven, instead hypothesis‐based, methods predict persistence. Methods Through Swedish Rheumatology Quality Register, linked other data sources, we identified a cohort 5475...
The 155-kDa plasma glycoprotein factor H (FH), which consists of 20 complement control protein (CCP) modules, protects self-tissue but not foreign organisms from damage by the cascade. Protection is achieved selective engagement FH, via CCPs 1–4, 6–8 and 19–20, with polyanion-rich host surfaces that bear covalently attached, activation-specific, fragments component C3. role intervening 9–18 in this process obscured lack structural knowledge. We have concatenated new high-resolution solution...
Characterization of segmental flexibility is needed to understand the biological mechanisms very large category functionally diverse proteins, exemplified by regulators complement activation, that consist numerous compact modules or domains linked short, potentially flexible, sequences amino acid residues. The use NMR-derived residual dipolar couplings (RDCs), in magnetically aligned media, evaluate interdomain motion established but only for two-domain proteins. We focused on three...
To define pharmacodynamic and efficacy biomarkers in ulcerative colitis [UC] patients treated with PF-00547659, an anti-human mucosal addressin cell adhesion molecule-1 [MAdCAM-1] monoclonal antibody, the TURANDOT study. Transcriptome, proteome immunohistochemistry data were generated peripheral blood intestinal biopsies from 357 subjects In blood, C-C motif chemokine receptor 9 [CCR9] gene expression demonstrated a dose-dependent increase relative to placebo, but inflamed CCR9 decreased...
Abstract Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic inflammation and mediated multiple immune cell types. In this work, we aimed to determine the relevance of changes in proportions peripheral blood mononuclear cells (PBMCs) during development following treatment. Samples from healthy donors, newly diagnosed RA patients, established patients that had inadequate response MTX were about start tumor necrosis factor inhibitors (TNFi) treatment collected before...
Diversity selection is a frequently applied strategy for assembling high-throughput screening libraries, making the assumption that diverse compound set increases chances of finding bioactive molecules. Based on previous work experimental 'affinity fingerprints', in this study, novel diversity method benchmarked utilizes predicted bioactivity profiles as descriptors. Compounds were selected based their activity against half targets (training set), and was assessed coverage remaining (test...
High Throughput Screening (HTS) is a common approach in life sciences to discover chemical matter that modulates biological target or phenotype. However, low assay throughput, reagents cost, flowchart can deal with only limited number of hits may impair screening large numbers compounds. In this case, subset compounds assayed, and silico models are utilized aid iterative design, usually expand around the found enrich subsequent rounds for relevant matter. lead an overly narrow focus,...
Adverse drug reactions (ADRs) are associated with most drugs, often discovered late in development and sometimes only during extended course of clinical use.
Abstract Background Defining clinical phenotypes provides opportunities for new diagnostics and may provide insights into early intervention disease prevention. There is increasing evidence that patient-derived health data contain information complements traditional methods of phenotyping. The utility these defining meaningful phenotypic groups great interest because social media online resources make it possible to query large cohorts patients with conditions. Methods We evaluated the...
Monogenic diseases have been shown to contribute complex disease risk and may hold new insights into the underlying biological mechanism of Inflammatory Bowel Disease (IBD).We analyzed Mendelian associations with IBD using over 55 million patients from Optum's deidentified electronic health records dataset database. Using significant diseases, we performed pathway enrichment analysis constructed a model gene expression datasets differentiate Crohn's (CD), ulcerative colitis (UC), healthy...
Abstract The ability to predict health outcomes from gene expression would catalyze a revolution in molecular diagnostics. This task is complicated because data are high dimensional whereas each experiment usually small (e.g., ∼ 20,000 genes may be measured for 100 subjects). However, thousands of transcriptomics experiments with hundreds samples available public repositories. Can representation learning techniques leverage these improve predictive performance on other tasks? Here, we report...
Abstract Currently existing solutions rarely protect message integrity, authenticity and user anonymity without burdening the with details of key management. To address this problem, we present Aldeon-a protocol for anonymous group conversations in a peer-to-peer system. The efficiency Aldeon is based on novel tree synchronization algorithm, which proposed discussed paper. By using significant reduction number exchanged messages achieved. In paper, formal definition hash branch function...