multi-mapping
Dotaz
Zobrazit nápovědu
Background: The Medical Information Database Network (MID-NET) is a national project that promotes effective safety measures for the active surveillance of drug safety assessments through pharmacoepidemiological methods, using real-world data in Japan. The MID-NET contains the data of approximately 5.05 million patients (as of December 2019) across 10 medical institutions, including 23 hospitals. One of the most important conditions for conducting pharmacoepidemiological research using multiple medical databases is to systematically verify of data standardization. Objectives: To evaluate the effect of improving the accuracy of standard data quality control by the development of a validation model for standard code mapping in multiple medical information databases. Methods: We established the standard code mapping validation center at one of the cooperating medical institutions of the MID-NET that could collect and manage information about the standard code interoperability. Additionally, we used the mapping table for the four standard codes, including the Japan Laboratory Test Standard Code, 10th Revision (JLAC10) code were collected from MID-NET cooperating institutions, and the accuracy of the mapping table was evaluated. Results: The observed four standard codes mapping ratio between institutions varied from >2,000 to <100. Moreover, the accuracies of standard codes were not standardized. We used a centralized standard code mapping validation model to provide feedback for standardizing JLAC-10 for each institution and meaningful differences between institutions were improved. Conclusions: The developed model visualized information differences and improved the data quality between multiple medical institutions.
INTRODUCTION: This report deals with advanced processing of blood oxygenation-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals. It does not address functional characteristics of the human cortex, such as functional connectivity. fMRI is based on measurement of BOLD variations of transverse relaxation time T2* or T2 . T2* or T2 can be calculated when multiple echoes of the MRI signal are recorded and may be more resistant to artifacts or better characterize tissue properties than the echoes themselves. OBJECTIVES: To develop a robust-to-noise algorithm for dynamic T2* mapping from a three gradient-echo (GRE) signal, allowing exploration of the potential of quantitative T2* mapping. METHODS: fMRI resting-state and block-design visual task three-echo data were acquired from nine healthy volunteers. A significant problem in multi-echo T2* fitting is the noise in the echoes. The majority of BOLD-denoising methods first pinpoint some source of noise and subsequently remove the respective noise time series. We instead first postulated that the blood oxygenation changes smoothly and consequently developed a state-of-the-art denoising algorithm that minimizes total variation (TV), enforcing smoothness in the processed BOLD echoes while preserving local temporal signal means. To ensure that calculated T2* time courses are also smooth, they were estimated from TV-denoised echoes. We used a denoising approach initially proposed by Professor Stanley Osher for two-dimensional (2D) images that has been very successful, most prominently in space research, where it enabled the reconstruction of the first-ever image of a black hole. To our knowledge, Osher's approach has so far not been used elsewhere for the denoising of one-dimensional fMRI time series. RESULTS: Signal-to-noise and contrast-to-noise distributions of the denoised echoes, as well as of the T2* time series, were superior to those obtained by the current fMRI denoising methods (3dDespike, tedana, NORDIC). The denoised echoes and the T2* time courses match the shape of the theoretical hemodynamic function much better than previous results. CONCLUSION: The TV-minimizing fMRI time series denoising algorithm yields denoised echoes of unprecedented quality, enabling estimation of smooth, dynamic T2* maps, i.e., a transition from qualitative-only fMRI echoes to fMRI signals endowed with time units.
- Publikační typ
- časopisecké články MeSH
Ever since the introduction of high-throughput sequencing following the human genome project, assembling short reads into a reference of sufficient quality posed a significant problem as a large portion of the human genome-estimated 50-69%-is repetitive. As a result, a sizable proportion of sequencing reads is multi-mapping, i.e., without a unique placement in the genome. The two key parameters for whether or not a read is multi-mapping are the read length and genome complexity. Long reads are now able to span difficult, heterochromatic regions, including full centromeres, and characterize chromosomes from "telomere to telomere". Moreover, identical reads or repeat arrays can be differentiated based on their epigenetic marks, such as methylation patterns, aiding in the assembly process. This is despite the fact that long reads still contain a modest percentage of sequencing errors, disorienting the aligners and assemblers both in accuracy and speed. Here, I review the proposed and implemented solutions to the repeat resolution and the multi-mapping read problem, as well as the downstream consequences of reference choice, repeat masking, and proper representation of sex chromosomes. I also consider the forthcoming challenges and solutions with regards to long reads, where we expect the shift from the problem of repeat localization within a single individual to the problem of repeat positioning within pangenomes.
- MeSH
- centromera chemie MeSH
- délka genomu MeSH
- genom lidský * MeSH
- lidé MeSH
- mapování chromozomů metody MeSH
- metylace DNA MeSH
- mikrosatelitní repetice * MeSH
- pohlavní chromozomy chemie MeSH
- telomery chemie MeSH
- výpočetní biologie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
[1st ed.] xiii, 528 s., obr.
Bipolar disorder is a leading contributor to the global burden of disease1. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown2. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.8 million controls), combining clinical, community and self-reported samples. We identified 298 genome-wide significant loci in the multi-ancestry meta-analysis, a fourfold increase over previous findings3, and identified an ancestry-specific association in the East Asian cohort. Integrating results from fine-mapping and other variant-to-gene mapping approaches identified 36 credible genes in the aetiology of bipolar disorder. Genes prioritized through fine-mapping were enriched for ultra-rare damaging missense and protein-truncating variations in cases with bipolar disorder4, highlighting convergence of common and rare variant signals. We report differences in the genetic architecture of bipolar disorder depending on the source of patient ascertainment and on bipolar disorder subtype (type I or type II). Several analyses implicate specific cell types in the pathophysiology of bipolar disorder, including GABAergic interneurons and medium spiny neurons. Together, these analyses provide additional insights into the genetic architecture and biological underpinnings of bipolar disorder.
- MeSH
- Asijci genetika MeSH
- běloch MeSH
- běloši genetika MeSH
- bipolární porucha * genetika MeSH
- celogenomová asociační studie * MeSH
- černoši nebo Afroameričané genetika MeSH
- fenotyp * MeSH
- GABAergní neurony metabolismus MeSH
- genetická predispozice k nemoci MeSH
- genomika * MeSH
- Hispánci a Latinoameričané genetika MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Chromosomal inversions occur in natural populations of many species, and may underlie reproductive isolation and local adaptation. Traditional methods of inversion discovery are labor-intensive and lack sensitivity. Here, we report the use of three-dimensional contact probabilities between genomic loci as assayed by chromosome-conformation capture sequencing (Hi-C) to detect multi-megabase polymorphic inversions in four barley genotypes. Inversions are validated by fluorescence in situ hybridization and Bionano optical mapping. We propose Hi-C as a generally applicable method for inversion discovery in natural populations.
Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional independent risk loci. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. Here, we conduct a multi-population GWAS meta-analysis in 38,463 participants (2440 cases). We then conduct conditional analyses and population specific GWAS. We discover twelve significant associations-eight from the multi-population meta-analysis (four novel), two from the multi-population conditional analysis (one novel), and two additional novel loci from the European meta-analysis. Fine-mapping implicates specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk locus. Non-HLA loci colocalize with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs is lacking but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associates with earlier disease onset. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cell-specific insights into its molecular drivers. Evaluating these associations in additional cohorts will refine our understanding of population specificity, heterogeneity, and clinical and molecular associations.
- MeSH
- celogenomová asociační studie * MeSH
- dítě MeSH
- genetická predispozice k nemoci MeSH
- haplotypy MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- nefrotický syndrom * genetika MeSH
- rizikové faktory MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
In this retrospective study we analysed changes of the ST segment in patients with arterial hypertension using multi-lead body surface mapping of the electric heart field as the ST segment often shows non-specific changes and is influenced by many different conditions. We constructed isointegral maps (IIM) of chosen intervals (the first 35 ms, the first 80 ms, and the whole ST segment) in 42 patients with arterial hypertension (with and without left ventricular hypertrophy) and in the control group involving 23 healthy persons. We analysed the position and values of map extrema. Spatial distribution of voltage integrals was similar in the control group and in the “pure” hypertensives. Patients with the left ventricular hypertrophy exhibited shifts of the integral minima. Despite our expectations, the highest extrema values were found in the control group and not in the left ventricular hypertrophy group. The extrema values were similar in all hypertensives, with or without left ventricular hypertrophy. Differences could be explained neither by the influence of the age, nor by the body habitus.
- MeSH
- dospělí MeSH
- hypertenze komplikace patofyziologie MeSH
- hypertrofie levé komory srdeční komplikace patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mapování potenciálů tělesného povrchu metody MeSH
- modely kardiovaskulární MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
