Leveraging supervised learning for functionally informed fine-mapping of cis-eQTLs identifies an additional 20,913 putative causal eQTLs

The large majority of variants identified by GWAS are non-coding, motivating detailed characterization of the function of non-coding variants. Experimental methods to assess variants’ effect on gene expressions in native chromatin context via direct perturbation are low-throughput. Existing high-throughput computational predictors thus have lacked large gold standard sets of regulatory variants for training and validation. Here, we leverage a set of 14,807 putative causal eQTLs in humans obtained through statistical fine-mapping, and we use 6121 features to directly train a predictor of whether a variant modifies nearby gene expression. We call the resulting prediction the expression modifier score (EMS). We validate EMS by comparing its ability to prioritize functional variants with other major scores. We then use EMS as a prior for statistical fine-mapping of eQTLs to identify an additional 20,913 putatively causal eQTLs, and we incorporate EMS into co-localization analysis to identify 310 additional candidate genes across UK Biobank phenotypes.

High-precision calculation of relativistic corrections for hydrogen-like atoms with screened Coulomb potentials

The first-order relativistic corrections to the non-relativistic energies of hydrogen-like atom embedded in plasma screening environments are calculated in the framework of direct perturbation theory by using the generalized pseudospectral method. The standard Debye-Hückel potential, exponential cosine screened Coulomb potential, and Hulthén potential are employed to model different screening conditions and their effects on the eigenenergies of hydrogen-like atoms are investigated. The relativistic corrections which include the relativistic mass correction, Darwin term, and the spin-orbit coupling term for both the ground and excited states are reported as functions of screening parameters. Comparison with previous theoretical predictions shows that both the relativistic mass correction and spin-orbit coupling obtained in this work are in good agreement with previous estimations, while significant discrepancy and even opposite trend is found for the Darwin term. The overall relativistic-corrected system energies predicted in this work, however, are in good agreement with the fully relativistic calculations available in the literature. We finally present the scaling law of the first-order relativistic corrections and discuss the validity of the direct perturbation theory with respect to both the nuclear charge and the screening parameter.

Leveraging supervised learning for functionally-informed fine-mapping of cis-eQTLs identifies an additional 20,913 putative causal eQTLs

The large majority of variants identified by GWAS are non-coding, motivating detailed characterization of the function of non-coding variants. Experimental methods to assess variants’ effect on gene expressions in native chromatin context via direct perturbation are low-throughput. Existing high-throughput computational predictors thus have lacked large gold standard sets of regulatory variants for training and validation. Here, we leverage a set of 14,807 putative causal eQTLs in humans obtained through statistical fine-mapping, and we use 6,121 features to directly train a predictor of whether a variant modifies nearby gene expression. We call the resulting prediction the expression modifier score (EMS). We validate EMS by comparing its ability to prioritize functional variants with other major scores. We then use EMS as a prior for statistical fine-mapping of eQTLs to identify an additional 20,913 putatively causal eQTLs, and we incorporate EMS into co-localization analysis to identify 310 additional candidate genes across UK Biobank phenotypes.

Comparison of complete and simplified models in terms of eigenvalues of cyclically symmetric ring structures

This work examines the free and parametric vibrations of constrained cyclically symmetric ring structures and compares the restrictions from different modeling assumptions. A complete model and two simplified models are developed by introducing different restrictions on deflections. The eigenvalues are formulated by direct perturbation and mode superposition. The results verify that they are comparable on the condition that the stiffness ratio of the rotating support to ring bending is relatively small. The eigenvalue splitting, parametric instability and their relationships are determined in closed form. The simplified models can correctly predict the splitting behavior before or after the loci veering. Two types of models obtain the same rules governing the instability, but the simplified models cannot accurately approach the time-evolution of the instability. Hence, it needs to be cautious to use the simplified models to estimate the instability behaviors for a cyclically symmetric ring structure with larger stiffness ratios especially within the loci veering range. Main results are verified by numerical calculations.

Direct perturbation analysis on the localized waves of the modified nonlinear Schrödinger equation under nonvanishing boundary condition

In this paper, the modified nonlinear Schrödinger equation is investigated via the direct perturbation method, which can describe the femtosecond optical pulse propagation in a monomodal optical fiber. Considering the quintic nonlinear perturbation, we obtain the approximate solution with the first-order correction, which can be expressed by the solution and symmetry of the derivative nonlinear Schrödinger equation. Under the nonvanishing boundary conditions, the approximate dark and anti-dark soliton solutions are derived and the existence conditions are also given. The effects of the perturbation on the propagations and interactions of the solitons on the nonzero background are discussed by comparing the physical quantities of solitons with the unperturbed case. It is found that the quintic nonlinear perturbation can lead to the change of the velocity as well as the pulse compression, but has no influence on the dynamics of the elastic interactions. Finally, numerical simulations are performed to support the theoretical results.