Magnetoencephalography (MEG) provides dynamic spatial‐temporal insight for neural activities in the cortex. Because the possible number of sources is far greater than the number of MEG detectors, the proposition to l...
Magnetoencephalography (MEG) provides dynamic spatial‐temporal insight for neural activities in the cortex. Because the possible number of sources is far greater than the number of MEG detectors, the proposition to localize sources directly from MEG data is ill‐posed. Here we develop a novel approach based on a sequence of data processing procedures that includes a clustering process, an intersection analysis, and an application of the maximum entropy method. We examine the performance of our method and compare it with the minimum‐norm least‐square inverse method using an artificial noisy MEG data.
The experimental and computational techniques for capturing information about protein structures and genetic variation within the human genome have advanced dramatically in the past 20 years, generating extensive new ...
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The experimental and computational techniques for capturing information about protein structures and genetic variation within the human genome have advanced dramatically in the past 20 years, generating extensive new data resources. In this review, we discuss these advances, along with new approaches for determining the impact a genetic variant has on protein function. We focus on the potential of new methods that integrate human genetic variation into protein structures to discover relationships to disease, including the discovery of mutational hotspots in cancer-related proteins, the localization of protein-altering variants within protein regions for common complex diseases, and the assessment of variants of unknown significance for Mendelian traits. We expect that approaches that integratethese data sources will play increasingly important roles in disease gene discovery and variant interpretation.
BACKGROUND:Splicing variants are a major class of pathogenic mutations, with their severity equivalent to nonsense mutations. However, redundant and degenerate splicing signals hinder functional assessments of sequenc...
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BACKGROUND:Splicing variants are a major class of pathogenic mutations, with their severity equivalent to nonsense mutations. However, redundant and degenerate splicing signals hinder functional assessments of sequence variations within introns, particularly at branch sites. We have established a massively parallel splicing assay to assess the impact on splicing of 11,191 disease-relevant variants. Based on the experimental results, we then applied regression-based methods to identify factors determining splicing decisions and their respective weights.
RESULTS:Our statistical modeling is highly sensitive, accurately annotating the splicing defects of near-exon intronic variants, outperforming state-of-the-art predictive tools. We have incorporated the algorithm and branchpoint information into a web-based tool, SpliceAPP, to provide an interactive application. This user-friendly website allows users to upload any genetic variants with genome coordinates (e.g., chr15 74,687,208 A G), and the tool will output predictions for splicing error scores and evaluate the impact on nearby splice sites. Additionally, users can query branch site information within the region of interest.
CONCLUSIONS:In summary, SpliceAPP represents a pioneering approach to screening pathogenic intronic variants, contributing to the development of precision medicine. It also facilitates the annotation of splicing motifs. SpliceAPP is freely accessible using the link https://***/SpliceAPP . Source code can be downloaded at https://***/hsinnan75/SpliceAPP .
Objectives: Nontyphoidal Salmonella (NTS) is a major foodborne pathogen causing from acute gastroenteritis to bacteraemia, particularly in paediatric and elderly patients. Antimicrobial resistance of NTS, especially r...
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The International Knockout Mouse Consortium (IKMC) developed high throughput gene trapping and gene targeting pipelines that produced mostly conditional mutations of more than 18,500 genes in C57BL/6N mouse embryonic ...
Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in ...
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Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression.
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