scholarly journals Host methylation predicts SARS-CoV-2 infection and clinical outcome

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Iain R. Konigsberg ◽  
Bret Barnes ◽  
Monica Campbell ◽  
Elizabeth Davidson ◽  
Yingfei Zhen ◽  
...  
Keyword(s):  
Disease Severity ◽  
Peripheral Blood ◽  
Viral Infections ◽  
Association Studies ◽  
Genetic Association Studies ◽  
Machine Learning Techniques ◽  
Diagnosis And Prognosis ◽  
Longitudinal Measurements ◽  
Genome Wide ◽  
Learning Techniques

Abstract Background Since the onset of the SARS-CoV-2 pandemic, most clinical testing has focused on RT-PCR1. Host epigenome manipulation post coronavirus infection2–4 suggests that DNA methylation signatures may differentiate patients with SARS-CoV-2 infection from uninfected individuals, and help predict COVID-19 disease severity, even at initial presentation. Methods We customized Illumina’s Infinium MethylationEPIC array to enhance immune response detection and profiled peripheral blood samples from 164 COVID-19 patients with longitudinal measurements of disease severity and 296 patient controls. Results Epigenome-wide association analysis revealed 13,033 genome-wide significant methylation sites for case-vs-control status. Genes and pathways involved in interferon signaling and viral response were significantly enriched among differentially methylated sites. We observe highly significant associations at genes previously reported in genetic association studies (e.g.IRF7, OAS1). Using machine learning techniques, models built using sparse regression yielded highly predictive findings: cross-validated best fit AUC was 93.6% for case-vs-control status, and 79.1%, 80.8%, and 84.4% for hospitalization, ICU admission, and progression to death, respectively. Conclusions In summary, the strong COVID-19-specific epigenetic signature in peripheral blood driven by key immune-related pathways related to infection status, disease severity, and clinical deterioration provides insights useful for diagnosis and prognosis of patients with viral infections.

scholarly journals Host methylation predicts SARS-CoV-2 infection and clinical outcome

2021 ◽  
Author(s):  
Iain R. Konigsberg ◽  
Bret Barnes ◽  
Monica Campbell ◽  
Elizabeth Davidson ◽  
Yingfei Zhen ◽  
...  
Keyword(s):  
Disease Severity ◽  
Peripheral Blood ◽  
Viral Infections ◽  
Association Studies ◽  
Genetic Association Studies ◽  
Machine Learning Techniques ◽  
Diagnosis And Prognosis ◽  
Longitudinal Measurements ◽  
Genome Wide ◽  
Learning Techniques

Abstract Since the onset of the SARS-CoV-2 pandemic, most clinical testing has focused on RT-PCR. Host epigenome manipulation post coronavirus infection suggests that DNA methylation signatures may differentiate patients with SARS-CoV-2 infection from uninfected individuals, and help predict COVID-19 disease severity, even at initial presentation. We customized Illumina’s Infinium Methylation EPIC array to enhance immune response detection and profiled peripheral blood samples from 164 COVID-19 patients with longitudinal measurements of disease severity and 296 patient controls. Epigenome-wide association analysis revealed 13,033 genome-wide significant methylation sites for case-vs-control status. Genes and pathways involved in interferon signaling and viral response were significantly enriched among differentially methylated sites. We observe highly significant associations at genes previously reported in genetic association studies (e.g. IRF7, OAS1). Using machine learning techniques, models built using sparse regression yielded highly predictive findings: cross-validated best fit AUC was 93.6% for case-vs-control status, and 79.1%, 80.8%, and 84.4% for hospitalization, ICU admission, and progression to death, respectively. In summary, the strong COVID-19-specific epigenetic signature in peripheral blood driven by key immune related pathways related to infection status, disease severity, and clinical deterioration provides insights useful for diagnosis and prognosis of patients with viral infections.

scholarly journals Evaluation of genome-wide power of genetic association studies based on empirical data from the HapMap project

2007 ◽  
Vol 16 (20) ◽  
pp. 2494-2505 ◽  
Author(s):  
Yasuhito Nannya ◽  
Kenjiro Taura ◽  
Mineo Kurokawa ◽  
Shigeru Chiba ◽  
Seishi Ogawa
Keyword(s):  
Genetic Association ◽  
Empirical Data ◽  
Association Studies ◽  
Genetic Association Studies ◽  
Hapmap Project ◽  
Genome Wide

Role of Artificial Intelligence in Modeling Psychometrics to Detect Neurodevelopmental Disorders

2020 ◽  
pp. 213-227
Author(s):  
Navjot Singh ◽  
Amarjot Kaur
Keyword(s):  
Artificial Intelligence ◽  
Machine Learning ◽  
Neurodevelopmental Disorders ◽  
Machine Learning Techniques ◽  
Diagnosis And Prognosis ◽  
Processing Power ◽  
Learning Techniques ◽  
Numerous Data ◽  
Applications Of Machine Learning ◽  
Micro Patterns

The objective of the present chapter is to highlight applications of machine learning and artificial intelligence (AI) in clinical diagnosis of neurodevelopmental disorders. The proposed approach aims at recognizing behavioral traits and other cognitive aspects. The availability of numerous data and high processing power, such as graphic processing units (GPUs) or cloud computing, enabled the study of micro-patterns hundreds of times faster compared to manual analysis. AI, being a new technological breakthrough, enables study of human behavior patterns, which are hidden in millions of micro-patterns originating from human actions, reactions, and gestures. The chapter will also focus on the challenges in existing machine learning techniques and the best possible solution addressing those problems. In the future, more AI-based expert systems can enhance the accuracy of the diagnosis and prognosis process.

scholarly journals Concordance of genetic risk across migraine subgroups: Impact on current and future genetic association studies

Cephalalgia ◽  
2014 ◽  
Vol 35 (6) ◽  
pp. 489-499 ◽  
Author(s):  
Dale R Nyholt ◽  
Verneri Anttila ◽  
Bendik S Winsvold ◽  
Tobias Kurth ◽  
Hreinn Stefansson ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Association Studies ◽  
Meta Analysis ◽  
Genetic Association Studies ◽  
Population Based ◽  
Significant Heterogeneity ◽  
Single Nucleotide ◽  
Disease Spectrum ◽  
Genome Wide ◽  
Genetic Overlap

Background There has been intensive debate whether migraine with aura (MA) and migraine without aura (MO) should be considered distinct subtypes or part of the same disease spectrum. There is also discussion to what extent migraine cases collected in specialised headache clinics differ from cases from population cohorts, and how female cases differ from male cases with respect to their migraine. To assess the genetic overlap between these migraine subgroups, we examined genome-wide association (GWA) results from analysis of 23,285 migraine cases and 95,425 population-matched controls. Methods Detailed heterogeneity analysis of single-nucleotide polymorphism (SNP) effects (odds ratios) between migraine subgroups was performed for the 12 independent SNP loci significantly associated ( p < 5 × 10−8; thus surpassing the threshold for genome-wide significance) with migraine susceptibility. Overall genetic overlap was assessed using SNP effect concordance analysis (SECA) at over 23,000 independent SNPs. Results Significant heterogeneity of SNP effects ( phet < 1.4 × 10−3) was observed between the MA and MO subgroups (for SNP rs9349379), and between the clinic- and population-based subgroups (for SNPs rs10915437, rs6790925 and rs6478241). However, for all 12 SNPs the risk-increasing allele was the same, and SECA found the majority of genome-wide SNP effects to be in the same direction across the subgroups. Conclusions Any differences in common genetic risk across these subgroups are outweighed by the similarities. Meta-analysis of additional migraine GWA datasets, regardless of their major subgroup composition, will identify new susceptibility loci for migraine.

scholarly journals Statistical challenges for genome-wide association studies of suicidality using family data

2010 ◽  
Vol 25 (5) ◽  
pp. 307-309 ◽  
Author(s):  
J. Lasky-Su ◽  
C. Lange
Keyword(s):  
Association Studies ◽  
Statistical Tests ◽  
Genetic Association Studies ◽  
Genetic Effect ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genetic Etiology ◽  
Genome Wide ◽  
Family Based ◽  
Study Designs

AbstractThe etiology of suicide is complex in nature with both environmental and genetic causes that are extremely diverse. This extensive heterogeneity weakens the relationship between genotype and phenotype and as a result, we face many challenges when studying the genetic etiology of suicide. We are now in the midst of a genetics revolution, where genotyping costs are decreasing and genotyping speed is increasing at a fast rate, allowing genetic association studies to genotype thousands to millions of SNPs that cover the entire human genome. As such, genome-wide association studies (GWAS) are now the norm. In this article we address several statistical challenges that occur when studying the genetic etiology of suicidality in the age of the genetics revolution. These challenges include: (1) the large number of statistical tests; (2) complex phenotypes that are difficult to quantify; and (3) modest genetic effect sizes. We address these statistical issues in the context of family-based study designs. Specifically, we discuss several statistical extensions of family-based association tests (FBATs) that work to alleviate these challenges. As our intention is to describe how statistical methodology may work to identify disease variants for suicidality, we avoid the mathematical details of the methodologies presented.

Efficient estimation of disease odds ratios for follow-up genetic association studies

2017 ◽  
Vol 28 (7) ◽  
pp. 1927-1941
Author(s):  
Jiyuan Hu ◽  
Wei Zhang ◽  
Xinmin Li ◽  
Dongdong Pan ◽  
Qizhai Li
Keyword(s):  
Genetic Association ◽  
Association Studies ◽  
Genetic Association Studies ◽  
Efficient Estimation ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Odds Ratios ◽  
Genome Wide ◽  
Follow Up Studies

In the past decade, genome-wide association studies have identified thousands of susceptible variants associated with complex human diseases and traits. Conducting follow-up genetic association studies has become a standard approach to validate the findings of genome-wide association studies. One problem of high interest in genetic association studies is to accurately estimate the strength of the association, which is often quantified by odds ratios in case-control studies. However, estimating the association directly by follow-up studies is inefficient since this approach ignores information from the genome-wide association studies. In this article, an estimator called GFcom, which integrates information from genome-wide association studies and follow-up studies, is proposed. The estimator includes both the point estimate and corresponding confidence interval. GFcom is more efficient than competing estimators regarding MSE and the length of confidence intervals. The superiority of GFcom is particularly evident when the genome-wide association study suffers from severe selection bias. Comprehensive simulation studies and applications to three real follow-up studies demonstrate the performance of the proposed estimator. An R package, “GFcom”, implementing our method is publicly available at https://github.com/JiyuanHu/GFcom .

scholarly journals Multi-Level Attention Graph Neural Network for Clinically Interpretable Pathway-Level Biomarkers Discovery

2020 ◽  
Author(s):  
Xiaohan Xing ◽  
Fan Yang ◽  
Hang Li ◽  
Jun Zhang ◽  
Yu Zhao ◽  
...  
Keyword(s):  
Neural Network ◽  
Precision Medicine ◽  
Signaling Pathways ◽  
Disease Diagnosis ◽  
Machine Learning Techniques ◽  
Proteomic Data ◽  
Diagnosis And Prognosis ◽  
Learning Techniques ◽  
Multi Level ◽  
Pathway Level

Precision medicine, regarded as the future of healthcare, is gaining increasing attention these years. As an essential part of precision medicine, clinical omics have been successfully applied in disease diagnosis and prognosis using machine learning techniques. However, existing methods mainly make predictions based on gene-level individual features or their random combinations, none of the previous work has considered the activation of signaling pathways. Therefore, the model interpretability and accuracy are limited, and reasonable signaling pathways are yet to be discovered. In this paper, we propose a novel multi-level attention graph neural network (MLA-GNN), which applies weighted correlation network analysis (WGCNA) to format the omic data of each patient into graph-structured data, and then constructs multi-level graph features, and fuses them through a well-designed multi-level graph feature fully fusion (MGFFF) module to conduct multi-task prediction. Moreover, a novel full-gradient graph saliency mechanism is developed to make the MLA-GNN interpretable. MLA-GNN achieves state-of-the-art performance on transcriptomic data from TCGA-LGG/TCGA-GBM and proteomic data from COVID-19/non-COVID-19 patient sera. More importantly, the proposed model's decision can be interpreted in the signaling pathway level and is consistent with the clinical understanding.

scholarly journals Controlling the Rate of GWAS False Discoveries

2016 ◽  
Author(s):  
Damian Brzyski ◽  
Christine B. Peterson ◽  
Piotr Sobczyk ◽  
Emmanuel J. Candés ◽  
Malgorzata Bogdan ◽  
...  
Keyword(s):  
Association Studies ◽  
Genetic Association Studies ◽  
R Package ◽  
Dependence Structure ◽  
Genome Wide Association Studies ◽  
Genomic Locus ◽  
Novel Approach ◽  
Genome Wide ◽  
Single Marker ◽  
False Discoveries

AbstractWith the rise of both the number and the complexity of traits of interest, control of the false discovery rate (FDR) in genetic association studies has become an increasingly appealing and accepted target for multiple comparison adjustment. While a number of robust FDR controlling strategies exist, the nature of this error rate is intimately tied to the precise way in which discoveries are counted, and the performance of FDR controlling procedures is satisfactory only if there is a one-to-one correspondence between what scientists describe as unique discoveries and the number of rejected hypotheses. The presence of linkage disequilibrium between markers in genome-wide association studies (GWAS) often leads researchers to consider the signal associated to multiple neighboring SNPs as indicating the existence of a single genomic locus with possible influence on the phenotype. This a posteriori aggregation of rejected hypotheses results in inflation of the relevant FDR. We propose a novel approach to FDR control that is based on pre-screening to identify the level of resolution of distinct hypotheses. We show how FDR controlling strategies can be adapted to account for this initial selection both with theoretical results and simulations that mimic the dependence structure to be expected in GWAS. We demonstrate that our approach is versatile and useful when the data are analyzed using both tests based on single marker and multivariate regression. We provide an R package that allows practitioners to apply our procedure on standard GWAS format data, and illustrate its performance on lipid traits in the NFBC66 cohort study.

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