Discover, rate, and verify biology preprints.

GROMTools: scalable individual-level GReX imputation for mega-biobank-scale cohorts

GROMTools, a sparse-weight C++/R engine streaming PLINK2 genotypes, reproduces PrediXcan and PLINK2 GReX imputations with about 100-fold less CPU time and 33-fold less peak memory.

CycloCross: Adversarial single-cell RNA-seq data translation across species

Translating cells between mouse, macaque and human scRNA-seq with a CycleGAN, without ortholog mapping, preserved developmental time structure, imputed missing states and produced more realistic synthetic cells than scGAN.

Rapid spatial cognition in mice, with and without neocortex and hippocampus

Naive mice learn a 9-turn route in a reconfigurable 3D maze within about 20 rewards; mutants lacking neocortex and hippocampus also learn, remember and generalize, though early exploration is inefficient.

TxCyto: A machine learning framework for estimating cytokine activity from whole transcriptome

A fully connected neural network trained on 9491 TCGA bulk tumor transcriptomes estimates activity of 645 cytokines and secreted proteins, checked against perturbation and protein data.

Intrinsic timescale develops hierarchically from sensorimotor to association cortex in youth and stabilizes in adulthood

Resting-state fMRI intrinsic timescale lengthens with age in association, not sensorimotor, cortex during ages 8-22, following the sensorimotor-association axis in two cohorts; it is largely age-stable in young adults.

Experiment-anchored abundance-coverage frontiers define conditional RHSVV exposure requirements in TP53-missense tumors

Experiment-anchored sweep of p53 abundance thresholds in CPTAC TP53-missense tumors maps how much RHSVV exposure contrast is needed as target coverage falls.

Prion Protein Deficiency Results in Synaptic, Neural Network and Behavioral Alterations

Lifelong prion protein (PrP) loss in mice lowers excitatory synaptic proteins, makes network bursts in mature cortical cultures rarer and neuronal activity more correlated, and increases adult dimming-disk escapes.

Human protein complex interfaces reveal candidate assembly roles for initiator methionine excision

N-terminal positions whose residue 2 permits methionine aminopeptidase cleavage are less often buried at human assembly interfaces (37.5% vs 47.5%), yet 175 such proteins stay engaged after boundary filtering.

A cortical basis for perception of internal gut sensations

Mice can report optogenetic activation of vagal gut mechanosensory neurons; insular cortex encodes perceptual report and causally affects detection only in a difficult psychophysics task, not simple detection.

A Taxonomy-Informed Sparse DNA Foundation Model for Microbial Genomics

A sparse mixture-of-experts DNA model conditioned on hyperbolic taxonomy embeddings learns better microbial representations than its taxonomy-free twin and comes close to Evo2-7B in probing and fine-tuning at lower compute.

AnnoAudit: a marker-based protocol for auditing single-cell atlas annotations reveals systematic, state-dependent annotation failure in a widely used traumatic brain injury resource

A marker audit finds 97.9% of CEREBRI's 45,051 official 'glutamatergic neuron' cells are not glutamatergic (four-check composite 82.6%), creating false ion-channel and OXPHOS signals; true neurons show acute KCNC3 up-regulation.

Accessing Enzyme Kinetic Data and Prediction Methods at Scale

OpenKinetics Predictor unifies thirteen enzyme kinetic predictors behind one interface and API; on E. coli iML1515, eight kcat predictors correlate pairwise at r 0.08 to 0.67.

kamino: fast proteome-wide variant calling for amino acid phylogenomics

Proteome-wide variant calling builds amino acid phylogenomic alignments orders of magnitude faster than a BUSCO marker pipeline, with similar tree signal in three of four test taxa.

Environmental filtering and host identity collectively shape root-associated microbiomes of Ericaceae and ectomycorrhizal plants in fumarole fields

Few root-associated microbial operational taxonomic units (OTUs) in Japanese fumarole fields prefer both a habitat and a host; most specialize on one axis, and Hyaloscyphaceae preferences lack significant phylogenetic signal.

HiMaLAYAS: enrichment-based annotation and visualization of hierarchically clustered matrices

HiMaLAYAS, a Python package, cuts dendrograms, tests clusters for categorical annotation enrichment (hypergeometric, Benjamini-Hochberg FDR), and renders significant annotations beside clustered heatmaps in one workflow.

sfate: Schur-free, target-conditioned absorption probabilities for scalable single-cell fate analysis

sfate computes annotation-targeted absorption probabilities by column-wise GMRES on a latent kNN graph, skipping Schur decomposition; a 74,984-cell mouse microglia analysis peaked at 1.76 GiB.

Beta2* Nicotinic Receptors Regulate Exploratory and Social Behavior Through Functionally Distinct Neuronal Populations

Beta2 nicotinic receptor knockdown in Htr3a-Cre mouse interneurons gave strong hypersociability; prefrontal NPY-Cre neurons, weaker effects (reduced social preference); striatal NPY neurons, slight effects mostly opposite to those.

A water-pinning hotspot drives templated tau aggregation

In a minimal tau fibril model, residue 300/301 binds incoming peptide first and carries the most release-prone hydration water. Spin-labelling site 300 impairs locking and suppresses seeded growth.

Evaluating the reliability of tools for mRNA annotation and IRES studies

A back-splicing circRNA reporter yields linear trans-spliced artifacts; in orthogonal assays three reported cellular IRESes are inactive, and Iso-Seq 5' ends agree with nAnT-iCAGE start sites.

Rewiring Oncogenic Transcriptional Complexes with Domain-ALTerAtion Chimeras (DALTACs) in Prostate Cancer

A bifunctional AR–p300/CBP molecule, DALTAC-1, forces a non-native contact between AR and p300 domains, silences AR enhancers and regresses AR-driven prostate tumors in mice while sparing AR-negative lines.