The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

A Nonstandard Path Integral Model for Curved Surface Analysis

The nonstandard finite-difference time-domain (NS-FDTD) method is implemented in the differential form on orthogonal grids, hence the benefit of opting for very fine resolutions in order to accurately treat curved surfaces in real-world applications, which indisputably increases the overall computational burden. In particular, these issues can hinder the electromagnetic design of structures with electrically-large size, such as aircrafts. To alleviate this shortcoming, a nonstandard path integral (PI) model for the NS-FDTD method is proposed in this paper, based on the fact that the PI form of Maxwell’s equations is fairly more suitable to treat objects with smooth surfaces than the differential form. The proposed concept uses a pair of basic and complementary path integrals for H-node calculations. Moreover, to attain the desired accuracy level, compared to the NS-FDTD method on square grids, the two path integrals are combined via a set of optimization parameters, determined from the dispersion equation of the PI formula. Through the latter, numerical simulations verify that the new PI model has almost the same modeling precision as the NS-FDTD technique. The featured methodology is applied to several realistic curved structures, which promptly substantiates that the combined use of the featured PI scheme greatly improves the NS-FDTD competences in the case of arbitrarily-shaped objects, modeled by means of coarse orthogonal grids

A Nonstandard Path Integral Model for Curved Surface Analysis

The nonstandard finite-difference time-domain (NS-FDTD) method is implemented in the differential form on orthogonal grids, hence the benefit of opting for very fine resolutions in order to accurately treat curved surfaces in real-world applications, which indisputably increases the overall computational burden. In particular, these issues can hinder the electromagnetic design of structures with electrically-large size, such as aircrafts. To alleviate this shortcoming, a nonstandard path integral (PI) model for the NS-FDTD method is proposed in this paper, based on the fact that the PI form of Maxwell’s equations is fairly more suitable to treat objects with smooth surfaces than the differential form. The proposed concept uses a pair of basic and complementary path integrals for H-node calculations. Moreover, to attain the desired accuracy level, compared to the NS-FDTD method on square grids, the two path integrals are combined via a set of optimization parameters, determined from the dispersion equation of the PI formula. Through the latter, numerical simulations verify that the new PI model has almost the same modeling precision as the NS-FDTD technique. The featured methodology is applied to several realistic curved structures, which promptly substantiates that the combined use of the featured PI scheme greatly improves the NS-FDTD competences in the case of arbitrarily-shaped objects, modeled by means of coarse orthogonal grids

Tuning of magnetosplamon coupling between graphene scatterers for the optimal design of adjustable metasurfaces

The resonance characteristics of magnetically-biased graphene micro-scatterers are thoroughly investigated in the present work using both eigenvalue and full-wave solvers. Initially, the graphene surface conductivity is presented in a tensor form due to the application of a magnetostatic bias field, which is perpendicular to the material’s surface. Then, the simple case of a graphene disk scatterer is examined, and a properly modified eigenvalue formulation is utilized to extract the plasmonic fundamental frequencies. The validity of the modal analysis is verified via a full-wave analysis that involves a plane-wave propagation and the extraction of the subsequent absorption cross-section utilizing the Finite-Difference Time-Domain method. Additionally, the dependence of a single disk scatterer resonances with the magnetostatic bias is evaluated, highlighting that as the bias field is increased, every edge mode degenerates into two sub-modes with an augmented difference between the resonant frequencies. Finally, the plasmonic coupling between adjacent scatterers is studied considering a periodic arrangement, similar to a metasurface, indicating the additional coupling modes as well as the adjustability of the properties with multiple degrees of freedom

Evaluation of magnetic field’s uniformity inside electromagnetic coils using graphene

The distribution of the magnetic field in electromagnetic coils, such as those employed in magnetic resonance imaging (MRI), is evaluated in this paper, through graphene gyrotropic properties. Initially, the rotation of an incident linearly polarized plane wave, due to an infinite graphene layer, is studied theoretically via the extraction of the perpendicular, to the polarization, electric component of the transmitted wave. Moreover, the influence of the magnetic bias field strength on this component is, also, examined, indicating the eligibility of graphene to detect magnetostatic field variations. To this aim, a specific device is proposed, consisting of a high frequency source, an electric field detector, and a finite graphene sheet that differs from the infinite one of the analytical case. To quantify the distance that the gyrotropic effects are detectable, the effective region is introduced and extracted via a properly modified finite-difference time-domain (FDTD) algorithm. The featured device is verified through a setup comprising a uniform electromagnetic coil, where the generated magnetostatic field is calculated at several cross-sections of the coil and compared to actual field values. Results indicate the accuracy and sensitivity of the designed device for the unambiguous regions