mixed model

Accelerating drug development in infectious diseases using zebrafish disease models supported by pharmacokinetic pharmacodynamic modeling as new approach methodology (NAM)

Zebrafish larva infection experiments plus pharmacokinetic-pharmacodynamic (PKPD) modelling gave bedaquiline's in vivo Emax and EC50 against M. marinum in about 2 months; waterborne clarithromycin barely entered larvae.

Impact of Rare and Common Genetic Variation on Cell Type-Specific Gene Expression

Single-cell eQTL mapping in 5.4 million PBMCs from 1,925 individuals with matched WGS finds common-variant eQTLs for 83% and rare-variant signals for 47% of 21,404 genes.

Structural and Energetic Determinants of Monobody Recognition of Oncogenic KRAS Variants

This study identifies structural and energetic determinants of monobody 12D4 recognition of KRAS variants using simulations and redesign, revealing key interactions and mutations for improved selectivity.

pyreml: a general-purpose, GPU-accelerated mixed model solver in Python

pyreml is a GPU-accelerated Python library for linear mixed models that outperforms existing closed-source REML software in speed and functionality.

Once in a blue moon: an unexpected evolutionary route to blue floral pigmentation in orchids

The paper investigates the genetic basis of blue floral pigmentation in orchids, finding an unexpected pathway involving duplicated genes and regulatory changes rather than the expected CYP75A pathway.

Distributed neural dynamics underlie the shift from movement preparation to execution

Magnetoencephalography during memory-guided finger sequences shows preparation and execution occupy distinct, partly overlapping subspaces; execution patterns appear first in hippocampus and last in M1, 160 ms before the first press.

The landscape of polygenic score prediction accuracy and transportability across the phenome in ancestrally diverse populations

This study evaluates polygenic score prediction accuracy and cross-ancestry portability across 3,994 PGSs in diverse populations, identifying factors affecting their performance and equity.

Integrative Multi-omics Analysis of the Human Skeletal Muscle Response to Endurance or Resistance Exercise: Findings from the Molecular Transducers of Physical Activity Consortium (MoTrPAC)

In 174 sedentary adults, resistance exercise changed more muscle molecular features than endurance exercise across omes and time points; network analysis nominates MEF2A and NFIC as regulatory hubs.

Accurate detection of metagenomic strain-level associations using average nucleotide identity with StrainSpy

StrainSpy fits zero-inflated beta mixed models to containment ANI, reaching >98% simulated sensitivity versus ~79% for logistic regression and detecting colorectal-cancer E. coli strain shifts.

The Sorghum Lipid Database (SoLD): population-scale lipidomics linking environmental and genetic variation in the Sorghum Association Panel

SoLD, a leaf lipidomics resource (244 species) for the Sorghum Association Panel across two field trials, reveals low-input sulfoquinovosyldiacylglycerol depletion, triacylglycerol enrichment, and environment-specific GWAS loci.

Transcriptionally distinct atypical B cell populations contribute to insulin autoreactivity and show differential activation, isotype switching, and somatic hypermutation in early-stage type 1 diabetes individuals

B cells from 24 early-stage type 1 diabetes individuals include four atypical clusters differing in switching and mutation; Cluster 10 had the highest insulin-binding antibody rate (5/16).

Fast pace of life is associated with host status in small mammals, despite pervasive surveillance bias

Arenavirus and hantavirus surveillance in small mammals tracks night-lights and accessibility; after adjusting for effort, fast-lived and synanthropic species are somewhat more often detected as hosts.

Tfh dysfunction is associated with poor responses to HBV vaccination

HBV vaccine-draining lymph node biopsies tie low antibody titers to reduced, interferon-skewed GNG4+ germinal center T follicular helper cells; public B cell clonotypes did not track response.

Late lactation represents the main window for sow-to-piglet transmission of persistent gut strains

Long-read 16S-ITS-23S tracking in 17 sow-piglet families shows maternal putative-strain sharing peaks in late lactation, which supplies most maternally derived strains persisting post-weaning.

An integrated pipeline to count individual transcripts with single-cell resolution

HCR3.0 RNA-FISH linked to RS-FISH spot detection labels transcripts in C. elegans embryos, larvae and adults, and yields per-neuron counts of short insulin-like peptide mRNAs in L2 larvae.

An open field phenomics resource for multimodal maize yield prediction across divergent environments

Drone imagery from 356 flights in 19 Genomes to Fields maize environments; vegetation-index functional principal components complement genomic kernels, predicting yield of held-out hybrids at r up to 0.501.

Suspected distortion of citations in high-impact cancer journals

Molecular oncology papers that textually resemble retracted paper mill papers receive 50 to 100% more citations yet fewer readers, cite one another, and measurably inflate some journals' citation rates.

Repeated drought induces a reproducible DNA methylation response associated with gene expression in Quercus lobata

Repeated drought in valley oak seedlings induced CHH hypermethylation recurring at the same gene-proximal transposable elements, associated with elevated yet methylation-attenuated expression of nearby genes.

Parallel evolution under constraint shapes echinocandin resistance in Candida auris

Across 681 matched isolates and 22,388 genomes, high-level micafungin resistance in Candida auris arises through recurrent FKS1 hotspot mutations amid strong purifying selection, and FKS2 appears dispensable.

Allosteric pathways govern Gα protein coupling selectivity at promiscuous GPCRs

The paper identifies allosteric pathways that determine G protein coupling selectivity in promiscuous GPCRs using a combination of mutagenesis, simulations, and machine learning.

Evaluating the Impact of Principal Component and Mixed Model Approaches on Polygenic Risk Score Portability to Diverse Ancestries in the UK Biobank

This study evaluates how principal component and mixed model approaches affect polygenic risk score portability across different ancestries in the UK Biobank.

Genetic canalization of nutrient resorption: evidence from a widespread grass under effective salt stress

In 110 common-garden Phragmites australis genotypes, effective salt stress left N, P and K resorption efficiency largely unchanged; efficiency instead tracked phylogeographic lineage, ecotype and latitude.

Brain morphological pattern is associated with the presence, severity, and transition of transdiagnostic psychiatric disorders in preadolescents

In 8,672 ABCD preadolescents, one canonical-correlation-derived brain morphology variate links higher cognition with lower psychopathology and tracks cumulative psychiatric diagnoses and 2-year diagnostic transitions.

Behavioral metabolic suppression confounds thermal performance estimates and climate vulnerability assessments in a marine ectotherm

In an undescribed intertidal Urticina anemone, heat-induced closure suppresses measured respiration, and fitted thermal performance curves place the critical thermal maximum far above the 25-30°C lethal range.

Development of an open-pollinated genetic mapping framework to facilitate the identification of QTL in apples

The paper develops an open-pollinated genetic mapping framework for apples to identify QTL, showing that MLMM outperforms MLM and demonstrating the feasibility of OP-based mapping for faster QTL discovery.

Visual Cortical Response Variability in Infants at High Familial Likelihood for Autism

Among infant siblings of autistic children, greater trial-to-trial variability in visual P1 latency at 6 and 12 months tracked higher 24-month cognitive and language scores; mean P1 measures did not.

DetectGxT: detecting gene-by-treatment interactions on molecular count phenotypes accounting for allelic additivity

R package DetectGxT fits allelic-additivity nonlinear models with optional donor or polygenic random effects, raising simulated power to detect gene-by-treatment interaction QTLs over linear regression.

Neural-vocal phase coupling reveals structured timing in birdsong production

In three singing canaries, sliding-window cross-correlation with surrogate testing shows HVC multi-unit activity and song envelope couple at a few preferred lags (positive, near-zero, negative), correlated or anticorrelated.

Extending Genome-Wide Association Studies to admixed cohorts with high degrees of relatedness

The paper introduces Tractor-Mix, a mixed model method for GWAS in admixed cohorts with high relatedness, improving ancestry-specific association detection and controlling false positives.

Dissociable Neural Responses to Conditioned Social Threats are Modulated by Spatial Proximity in PTSD and MDD

In 50 trauma-exposed veterans, thalamic hypoactivity to near virtual-reality threats tracked both PTSD and MDD severity, while amygdala hyperactivity to far threats tracked only PTSD severity.