Fast Photochemical Oxidation of Proteins (FPOP) is a promising technique for studying protein structure and dynamics. The quality of insight provided by FPOP depends on the reliability of the determination of the modification site. This study investigates the performance of two search engines, Mascot and PEAKS, for the data processing of FPOP analyses. Comparison of Mascot and PEAKS of the hemoglobin--haptoglobin Bruker timsTOF data set (PXD021621) revealed greater consistency in the Mascot identification of modified peptides, with around 26% of the IDs being mutual for all three replicates, compared to approximately 22% for PEAKS. The intersection between Mascot and PEAKS results revealed a limited number (31%) of shared modified peptides. Principal Component Analysis (PCA) using the peptide-spectrum match (PSM) score, site probability, and peptide intensity was applied to evaluate the results, and the analyses revealed distinct clusters of modified peptides. Mascot showed the ability to assess confident site determination, even with lower PSM scores. However, high PSM scores from PEAKS did not guarantee a reliable determination of the modification site. Fragmentation coverage of the modification position played a crucial role in Mascot assignments, while the AScore localizations from PEAKS often become ambiguous because the software employs MS/MS merging.
Allelic variability in the adaptive immune receptor loci, which harbor the gene segments that encode B cell and T cell receptors (BCR/TCR), is of critical importance for immune responses to pathogens and vaccines. Adaptive immune receptor repertoire sequencing (AIRR-seq) has become widespread in immunology research making it the most readily available source of information about allelic diversity in immunoglobulin (IG) and T cell receptor (TR) loci. Here, we present a novel algorithm for extrasensitive and specific variable (V) and joining (J) gene allele inference, allowing the reconstruction of individual high-quality gene segment libraries. The approach can be applied for inferring allelic variants from peripheral blood lymphocyte BCR and TCR repertoire sequencing data, including hypermutated isotype-switched BCR sequences, thus allowing high-throughput novel allele discovery from a wide variety of existing data sets. The developed algorithm is a part of the MiXCR software. We demonstrate the accuracy of this approach using AIRR-seq paired with long-read genomic sequencing data, comparing it to a widely used algorithm, TIgGER. We applied the algorithm to a large set of IG heavy chain (IGH) AIRR-seq data from 450 donors of ancestrally diverse population groups, and to the largest reported full-length TCR alpha and beta chain (TRA and TRB) AIRR-seq data set, representing 134 individuals. This allowed us to assess the genetic diversity within the IGH, TRA, and TRB loci in different populations and to establish a database of alleles of V and J genes inferred from AIRR-seq data and their population frequencies with free public access through VDJ.online database.
- MeSH
- alely * MeSH
- algoritmy * MeSH
- genetická variace MeSH
- lidé MeSH
- receptory antigenů B-buněk genetika imunologie MeSH
- receptory antigenů T-buněk genetika imunologie MeSH
- sekvenční analýza DNA metody MeSH
- software * MeSH
- vysoce účinné nukleotidové sekvenování metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: Ktrans$$ {K}^{\mathrm{trans}} $$ has often been proposed as a quantitative imaging biomarker for diagnosis, prognosis, and treatment response assessment for various tumors. None of the many software tools for Ktrans$$ {K}^{\mathrm{trans}} $$ quantification are standardized. The ISMRM Open Science Initiative for Perfusion Imaging-Dynamic Contrast-Enhanced (OSIPI-DCE) challenge was designed to benchmark methods to better help the efforts to standardize Ktrans$$ {K}^{\mathrm{trans}} $$ measurement. METHODS: A framework was created to evaluate Ktrans$$ {K}^{\mathrm{trans}} $$ values produced by DCE-MRI analysis pipelines to enable benchmarking. The perfusion MRI community was invited to apply their pipelines for Ktrans$$ {K}^{\mathrm{trans}} $$ quantification in glioblastoma from clinical and synthetic patients. Submissions were required to include the entrants' Ktrans$$ {K}^{\mathrm{trans}} $$ values, the applied software, and a standard operating procedure. These were evaluated using the proposed OSIPIgold$$ \mathrm{OSIP}{\mathrm{I}}_{\mathrm{gold}} $$ score defined with accuracy, repeatability, and reproducibility components. RESULTS: Across the 10 received submissions, the OSIPIgold$$ \mathrm{OSIP}{\mathrm{I}}_{\mathrm{gold}} $$ score ranged from 28% to 78% with a 59% median. The accuracy, repeatability, and reproducibility scores ranged from 0.54 to 0.92, 0.64 to 0.86, and 0.65 to 1.00, respectively (0-1 = lowest-highest). Manual arterial input function selection markedly affected the reproducibility and showed greater variability in Ktrans$$ {K}^{\mathrm{trans}} $$ analysis than automated methods. Furthermore, provision of a detailed standard operating procedure was critical for higher reproducibility. CONCLUSIONS: This study reports results from the OSIPI-DCE challenge and highlights the high inter-software variability within Ktrans$$ {K}^{\mathrm{trans}} $$ estimation, providing a framework for ongoing benchmarking against the scores presented. Through this challenge, the participating teams were ranked based on the performance of their software tools in the particular setting of this challenge. In a real-world clinical setting, many of these tools may perform differently with different benchmarking methodology.
- MeSH
- algoritmy MeSH
- kontrastní látky * MeSH
- lidé MeSH
- magnetická rezonanční tomografie * metody MeSH
- reprodukovatelnost výsledků MeSH
- software MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The inherent diversity of approaches in proteomics research has led to a wide range of software solutions for data analysis. These software solutions encompass multiple tools, each employing different algorithms for various tasks such as peptide-spectrum matching, protein inference, quantification, statistical analysis, and visualization. To enable an unbiased comparison of commonly used bottom-up label-free proteomics workflows, we introduce WOMBAT-P, a versatile platform designed for automated benchmarking and comparison. WOMBAT-P simplifies the processing of public data by utilizing the sample and data relationship format for proteomics (SDRF-Proteomics) as input. This feature streamlines the analysis of annotated local or public ProteomeXchange data sets, promoting efficient comparisons among diverse outputs. Through an evaluation using experimental ground truth data and a realistic biological data set, we uncover significant disparities and a limited overlap in the quantified proteins. WOMBAT-P not only enables rapid execution and seamless comparison of workflows but also provides valuable insights into the capabilities of different software solutions. These benchmarking metrics are a valuable resource for researchers in selecting the most suitable workflow for their specific data sets. The modular architecture of WOMBAT-P promotes extensibility and customization. The software is available at https://github.com/wombat-p/WOMBAT-Pipelines.
- MeSH
- analýza dat MeSH
- benchmarking * MeSH
- proteiny MeSH
- proteomika * MeSH
- průběh práce MeSH
- software MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- Mediately,
- MeSH
- digitální zdraví * MeSH
- lidé MeSH
- mobilní aplikace MeSH
- nádory prsu diagnóza MeSH
- nádory terapie MeSH
- protinádorové látky imunologicky aktivní aplikace a dávkování škodlivé účinky MeSH
- telemedicína MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- rozhovory MeSH
Lipidomics and metabolomics communities comprise various informatics tools; however, software programs handling multimodal mass spectrometry (MS) data with structural annotations guided by the Lipidomics Standards Initiative are limited. Here, we provide MS-DIAL 5 for in-depth lipidome structural elucidation through electron-activated dissociation (EAD)-based tandem MS and determining their molecular localization through MS imaging (MSI) data using a species/tissue-specific lipidome database containing the predicted collision-cross section values. With the optimized EAD settings using 14 eV kinetic energy, the program correctly delineated lipid structures for 96.4% of authentic standards, among which 78.0% had the sn-, OH-, and/or C = C positions correctly assigned at concentrations exceeding 1 μM. We showcased our workflow by annotating the sn- and double-bond positions of eye-specific phosphatidylcholines containing very-long-chain polyunsaturated fatty acids (VLC-PUFAs), characterized as PC n-3-VLC-PUFA/FA. Using MSI data from the eye and n-3-VLC-PUFA-supplemented HeLa cells, we identified glycerol 3-phosphate acyltransferase as an enzyme candidate responsible for incorporating n-3 VLC-PUFAs into the sn1 position of phospholipids in mammalian cells, which was confirmed using EAD-MS/MS and recombinant proteins in a cell-free system. Therefore, the MS-DIAL 5 environment, combined with optimized MS data acquisition methods, facilitates a better understanding of lipid structures and their localization, offering insights into lipid biology.
- MeSH
- data mining * metody MeSH
- fosfatidylcholiny metabolismus chemie MeSH
- HeLa buňky MeSH
- hmotnostní spektrometrie metody MeSH
- lidé MeSH
- lipidomika * metody MeSH
- lipidy chemie analýza MeSH
- metabolomika metody MeSH
- nenasycené mastné kyseliny metabolismus chemie MeSH
- software MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In response to our study, the commentary by Infanti et al. (2024) raised critical points regarding (i) the conceptualization and utility of the user-avatar bond in addressing gaming disorder (GD) risk, and (ii) the optimization of supervised machine learning techniques applied to assess GD risk. To advance the scientific dialogue and progress in these areas, the present paper aims to: (i) enhance the clarity and understanding of the concepts of the avatar, the user-avatar bond, and the digital phenotype concerning gaming disorder (GD) within the broader field of behavioral addictions, and (ii) comparatively assess how the user-avatar bond (UAB) may predict GD risk, by both removing data augmentation before the data split and by implementing alternative data imbalance treatment approaches in programming.
- MeSH
- avatar MeSH
- lidé MeSH
- netholismus * MeSH
- řízené strojové učení MeSH
- strojové učení * MeSH
- uživatelské rozhraní počítače MeSH
- videohry MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND AIMS: The question of when and how to treat truly asymptomatic patients with severe aortic stenosis (AS) and normal left ventricular (LV) systolic function is still subject to debate and ongoing research. Here, the results of extended follow-up of the AVATAR trial are reported (NCT02436655, ClinicalTrials.gov). METHODS: The AVATAR trial randomly assigned patients with severe, asymptomatic AS and LV ejection fraction ≥ 50% to undergo either early surgical aortic valve replacement (AVR) or conservative treatment with watchful waiting strategy. All patients had negative exercise stress testing. The primary hypothesis was that early AVR will reduce a primary composite endpoint comprising all-cause death, acute myocardial infarction, stroke, or unplanned hospitalization for heart failure (HF), as compared with conservative treatment strategy. RESULTS: A total of 157 low-risk patients (mean age 67 years, 57% men, mean Society of Thoracic Surgeons score 1.7%) were randomly allocated to either the early AVR group (n = 78) or the conservative treatment group (n = 79). In an intention-to-treat analysis, after a median follow-up of 63 months, the primary composite endpoint outcome event occurred in 18/78 patients (23.1%) in the early surgery group and in 37/79 patients (46.8%) in the conservative treatment group [hazard ratio (HR) early surgery vs. conservative treatment 0.42; 95% confidence interval (CI) 0.24-0.73, P = .002]. The Kaplan-Meier estimates for individual endpoints of all-cause death and HF hospitalization were significantly lower in the early surgery compared with the conservative group (HR 0.44; 95% CI 0.23-0.85, P = .012, for all-cause death and HR 0.21; 95% CI 0.06-0.73, P = .007, for HF hospitalizations). CONCLUSIONS: The extended follow-up of the AVATAR trial demonstrates better clinical outcomes with early surgical AVR in truly asymptomatic patients with severe AS and normal LV ejection fraction compared with patients treated with conservative management on watchful waiting.
- MeSH
- aortální chlopeň chirurgie MeSH
- aortální stenóza * chirurgie mortalita terapie MeSH
- asymptomatické nemoci terapie MeSH
- avatar MeSH
- cévní mozková příhoda MeSH
- chirurgická náhrada chlopně * metody MeSH
- hospitalizace statistika a číselné údaje MeSH
- konzervativní terapie * metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- pozorné vyčkávání MeSH
- senioři MeSH
- tepový objem fyziologie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
OBJECTIVE: Age-at-death estimation is usually done manually by experts. As such, manual estimation is subjective and greatly depends on the past experience and proficiency of the expert. This becomes even more critical if experts need to evaluate individuals with unknown population affinity or with affinity that they are not familiar with. The purpose of this study is to design a novel age-at-death estimation method allowing for automatic evaluation on computers, thus eliminating the human factor. METHODS: We used a traditional machine-learning approach with explicit feature extraction. First, we identified and described the features that are relevant for age-at-death estimation. Then, we created a multi-linear regression model combining these features. Finally, we analysed the model performance in terms of Mean Absolute Error (MAE), Mean Bias Error (MBE), Slope of Residuals (SoR) and Root Mean Squared Error (RMSE). RESULTS: The main result of this study is a population-independent method of estimating an individual's age-at-death using the acetabulum of the pelvis. Apart from data acquisition, the whole procedure of pre-processing, feature extraction and age estimation is fully automated and implemented as a computer program. This program is a part of a freely available web-based software tool called CoxAGE3D, which is available at https://coxage3d.fit.cvut.cz/. Based on our dataset, the MAE of the presented method is about 10.7 years. In addition, five population-specific models for Thai, Lithuanian, Portuguese, Greek and Swiss populations are also given. The MAEs for these populations are 9.6, 9.8, 10.8, 10.5 and 9.2 years, respectively. Our age-at-death estimation method is suitable for individuals with unknown population affinity and provides acceptable accuracy. The age estimation error cannot be completely eliminated, because it is a consequence of the variability of the ageing process of different individuals not only across different populations but also within a certain population.
- MeSH
- acetabulum * diagnostické zobrazování MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- lineární modely MeSH
- mladý dospělý MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- software * MeSH
- soudní antropologie * metody MeSH
- strojové učení * MeSH
- určení kostního věku * metody MeSH
- zobrazování trojrozměrné * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Remote measurement technology (RMT) involves the use of wearable devices and smartphone apps to measure health outcomes in everyday life. RMT with feedback in the form of data visual representations can facilitate self-management of chronic health conditions, promote health care engagement, and present opportunities for intervention. Studies to date focus broadly on multiple dimensions of service users' design preferences and RMT user experiences (eg, health variables of perceived importance and perceived quality of medical advice provided) as opposed to data visualization preferences. OBJECTIVE: This study aims to explore data visualization preferences and priorities in RMT, with individuals living with depression, those with epilepsy, and those with multiple sclerosis (MS). METHODS: A triangulated qualitative study comparing and thematically synthesizing focus group discussions with user reviews of existing self-management apps and a systematic review of RMT data visualization preferences. A total of 45 people participated in 6 focus groups across the 3 health conditions (depression, n=17; epilepsy, n=11; and MS, n=17). RESULTS: Thematic analysis validated a major theme around design preferences and recommendations and identified a further four minor themes: (1) data reporting, (2) impact of visualization, (3) moderators of visualization preferences, and (4) system-related factors and features. CONCLUSIONS: When used effectively, data visualizations are valuable, engaging components of RMT. Easy to use and intuitive data visualization design was lauded by individuals with neurological and psychiatric conditions. Apps design needs to consider the unique requirements of service users. Overall, this study offers RMT developers a comprehensive outline of the data visualization preferences of individuals living with depression, epilepsy, and MS.
- MeSH
- deprese * psychologie MeSH
- dospělí MeSH
- epilepsie * psychologie MeSH
- kvalitativní výzkum * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mobilní aplikace MeSH
- nositelná elektronika MeSH
- pacientova volba psychologie statistika a číselné údaje MeSH
- roztroušená skleróza * psychologie MeSH
- senioři MeSH
- telemedicína MeSH
- vizualizace dat MeSH
- zjišťování skupinových postojů * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
