Biology subjects

Liu, Z.

Publications and source records attributed to Liu, Z..

At least 163 records · Page 9Linked to original sources

bioRxiv2026

Preserved Embedding of Neural Population Activity for Brain Computer Interfaces

Inferring neural population dynamics from motor cortex recordings is essential for brain-computer interface (BCI) control. However, neural activity patterns during similar behaviors exhibit systematic variability across recording sessions, subjects, and task contexts due to neural plasticity, anatomical differences, and varying movement distances. This variability degrades BCI decoder performanc when applied to different sessions, subjects, and task contexts. Here, we introduce Multi-Aligned Neural Data Transformer (MANDT) that extracts consistent embeddings of the motor cortical dynamics. By learning these consistent embeddings, MANDT enables generalization of BCI decoding: a decoder trained on data from one session maintains robust performance when applied to new sessions without recalibration. We validated our approach on neural recordings from rhesus monkeys performing the delayed-reach task. Lastly, we show that CEBRA can be used for the robotic control, enabling direct neural control of a humanoid robot, allowing monkeys to guide complex robotic manipulation tasks through brain signal.

neuroscience↗

bioRxiv2026

A T-cell engager platform induces deep plasma cell depletion in autoimmune dry eye

Bispecific T cell engagers (TCEs) have transformed targeted immunotherapy but remain constrained by ex vivo manufacturing and systemic delivery, limiting their application in autoimmune disorders. Here, we introduce the first in vivo TCE platform, utilizing a T cell-targeted integration-deficient lentiviral vector (T-IDLE) to reprogram endogenous T cells into engineered T cells secreting BCMAxCD3 TCEs (STCEs) directly in vivo. In murine Sjogrens syndrome-associated dry eye model, a single intravenous administration of T-IDLESTCE achieved deep and sustained depletion of plasmablasts and plasma cells, reversing lacrimal gland inflammation and restoring tear production without detectable off-target transduction. Longitudinal studies in cynomolgus monkeys confirmed translational promise, demonstrating potent plasma cell clearance and favorable safety profiles over 12 weeks post-vector dosing. Mechanistic analyses demonstrated attenuation of Th1/Th17-mediated inflammation and controlled cytokine responses, accompanied by negligible vector integration in non-T cell lineages, thereby substantiating the safety profile of the integration-deficient design. This first-in-class in vivo TCE approach represents a manufacturing-free, scalable immunotherapy strategy for autoantibody-mediated diseases.

bioengineering↗

bioRxiv2026

Synergistic integration of inducible RNA switches enhances the manipulation of vector expression

Precise manipulation of gene expression is pivotal for gene function studies and the optimization of gene therapy. RNA-based gene switches are attractive tools due to their robust tunability by FDA-approved small molecules, the absence of exogenous immunogenic proteins, and the small size for gene delivery vectors such as adeno-associated virus (AAV). However, existing RNA switches only target a single step of gene expression such as transcription or RNA splicing, exhibiting intrinsic limitations in gene regulation. To overcome this issue, this study integrated the aptamer-based polyA regulator (pA), the drug-elicitable alternative splicing module (DreAM) and an engineered translation modulator with conditional upstream open reading frames (uORFs) to construct the DreAM-plus RNA switch. The pA-DreAM concatenation led to 1.5[~]5.0-fold and 1.2[~]4.4-fold increase of inducible fold changes than pA and DreAM, respectively. The uORF module further enhanced the switching performance by 1.4[~]6.3-fold. DreAM-plus-mediated transient transgene expression demonstrated a temporal resolution of about 24 hours and high tissue specificity to liver or heart. Critically, DreAM-plus achieved transient expression of an array of gene editors (SpCas9, SaCas9, Un1Cas12f1, OsCas12f1, AcCas12n, IsDra2 TnpB etc.) that significantly mitigated off-target effects by 1.4[~]2.8 folds in plasmids, lentivirus and AAV. In a new mouse model with lipid-nanoparticle-delivered pre-existing immunity, DreAM-plus attenuated AAV-delivered Cas-specific CD8 T cell immune toxicity in the liver and the heart. Therefore, multiple RNA switches could be synergistically integrated to build more sophisticated genetic cassettes for enhanced manipulation of gene expression.

bioengineering↗

bioRxiv2026

Looking backward for the future: long-term population recovery, habitat associations, and future climatic vulnerability of the critically endangered Sino-Mongolian beaver (Castor fiber birulai) in China

Despite the successful population recovery of the Eurasian beaver (Castor fiber) across much of Eurasia, its subspecies, the Sino-Mongolian beaver (C. f. birulai), remains critically endangered, with an estimated population of approximately 1,500 individuals confined to a small number of isolated and fragmented refugia along the China-Mongolia border. Effective conservation of this highly threatened subspecies requires a holistic perspective that integrates constraints on population dynamics, habitat associations, and future climatic vulnerability. Here, we combined systematic annual field surveys conducted between 2003 and 2023 with historical survey records from 1975 to 1989 in northern Xinjiang, China, to synthesize long-term spatiotemporal population dynamics, evaluate habitat preferences based on nine local environmental variables, and assess future climatic vulnerability using ensemble species distribution models (SDMs) under projected climate change scenarios. We detected a significant and phased population recovery, with beaver colony numbers increasing from 27 (approximately 100 individuals) in 1975 to 227 (681-908 individuals) in 2023. This recovery closely corresponded with major conservation milestones, including the establishment and upgrading of nature reserves, strengthened legislative protection, and enhanced multi-stakeholder collaboration. Habitat analyses further indicated that the Sino-Mongolian beaver preferentially occupied areas characterized by minimal anthropogenic disturbance and stable hydro-geomorphic conditions. Critically, SDM projections revealed that only 14% of the current study area presently exhibits high climatic suitability, and these highly suitable habitats are expected to disappear entirely by the 2050s. Together, our findings provide a comprehensive overview of the historical population recovery and conservation trajectory of the Sino-Mongolian beaver in China, and offer robust scientific support for developing adaptive management strategies in the face of ongoing climate change and increasing human pressures.

ecology↗

bioRxiv2026

TREM2 agonist antibody rebuilds the resident synovial macrophage lining barrier in rheumatoid arthritis

Rheumatoid arthritis (RA) can be viewed as a disease of barrier failure, in which CX3CR1+/TREM2+ synovial tissue-resident macrophages that form the lining barrier over cartilage and bone become fragmented and disorganized. However, how to therapeutically rebuild this barrier--and how macrophage states transition during repair--remain unclear. We engineered TR-Ab19, a mouse-selective agonistic antibody against TREM2, as a precision tool to initiate and interrogate barrier repair in vivo. TR-Ab19 engages TREM2-linked downstream signaling and redirects synovial macrophages from Clec4d+ inflammatory/proliferative programs toward TREM2+CX3CR1+Aqp1+ barrier-like states, thereby rebuilding the lining barrier. Across collagen-induced arthritis (CIA) and serum-transfer arthritis (STA) models, TR-Ab19 reduces synovitis, preserves cartilage and bone microarchitecture, limits osteoclastogenesis, and attenuates systemic cytokines and B-cell abnormalities. Single-cell RNA-seq with trajectory and cell-cell communication analyses reveal a TREM2-dependent shift toward a barrier-dominant macrophage ecosystem. Together, these findings establish antibody-mediated reprogramming of resident synovial macrophages as a barrier-centered strategy for RA and provide a framework for instructing macrophage niches in chronic inflammation.

bioengineering↗

bioRxiv2026

The genetic repertoire of the deep sea: from sequence to structure and function

The deep sea as the largest and maybe most hostile environment on Earth is still underexplored especially regarding its genetic repertoire. Yet, previous work has revealed significant habitat-specific deep-sea biodiversity. Here, we present an integrated deep-sea genetic dataset comprising 502 million nonredundant genes from 2,138 samples and 2.4 million predicted structures, and used it to link specific protein structures with genetic variants associated with life in the deep sea and to assess their biotechnology potential. Combining global sequence analysis with biophysical and biochemical measurements revealed unprecedented sequence diversity, yet substantial structural conservation of proteins. Especially proteins involved in replication, recombination, and repair were identified to be under rapid evolution and with specialized properties. Among these, a structurally divergent helicase exhibited advantages in controlling nanopore sequencing speed. Thus, our work positions the deep sea as a unique evolutionary engine that generates and hosts genetic diversity and bridges genetic knowledge with biotechnology.

bioinformatics↗

bioRxiv2026

Glycosylated GM-CSF expands B-1b cells and B-1b plasma cells and programs them for immunosuppression

The myeloid growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) exhibits paradoxical pro- and anti-inflammatory functions, but the factors determining these divergent outcomes remain unclear. Here, we report that this functional divergence is controlled by its glycosylation. Murine recombinant fully glycosylated GM-CSF (rgGM-CSF) specifically induces immunosuppressive cell types, whereas its recombinant non-glycosylated counterpart (rngGM-CSF) promotes effector immune cells. Using single-cell ATAC-sequencing and flow cytometry, we show that rgGM-CSF has a previously unrecognized ability to effectively expand IL-10+ LAG-3+ PD-L1+ B-1b plasma cells (PCs) with immunosuppressive properties and self reactive natural IgM secretion. Although rgGM-CSF also promotes the expansion of hematopoietic stem and progenitor cells (HSPCs) and monocytic myeloid-derived suppressor cells (M-MDSCs), adoptive transfer experiments demonstrate that the rgGM-CSF-induced B-1b PCs are responsible for an IL-10-dependent long-term protection in mice from experimental autoimmune-encephalomyelitis (EAE). Our data suggest that glycosylation enhances the systemic bioavailability and activity of GM-CSF and promotes the expansion of immunoregulatory cells rather than pro-inflammatory myeloid effector cells. Together, these results demonstrate that the dual activity of GM-CSF is controlled by its glycosylation, resulting in opposing immune functions. These findings support a re-evaluation of human rgGM-CSF (regramostim) as a potential therapeutic strategy for immunosuppression in transplantation and autoimmune diseases. Key pointsO_LIGlycosylated GM-CSF promotes B-1b cells and B-1b plasma cells expansion and establishes their long-term imprinting as IL-10+ LAG3+ PD-L1+ natural IgM secreting regulatory cells. C_LIO_LIAlbumin binding enhances the systemic activity of glycosylated GM-CSF in generating regulatory B-1b plasma cells. C_LIO_LIGlycosylated GM-CSF injections into mice expand M-MDSCs, but their suppressive iNOS production is only maintained short-term. C_LIO_LINon-glycosylated GM-CSF injections preferentially promote expansion of pro-inflammatory effector monocytes and neutrophils. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=179 HEIGHT=200 SRC="FIGDIR/small/703206v1_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@1814c57org.highwire.dtl.DTLVardef@1bb0e95org.highwire.dtl.DTLVardef@1ba8011org.highwire.dtl.DTLVardef@12df69f_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2026

Symmetric Fusion of fMRI and EEG for Spectrally Resolved Functional Neuroimaging

Simultaneous electroencephalography (EEG) and functional MRI (fMRI) offers complementary sensitivity to fast electrophysiological dynamics of EEG and spatially resolved hemodynamics of fMRI, yet previous joint-analysis approaches are confined to fixed task paradigms and struggle with continuous or naturalistic brain states. We FSINC (Fusing Source Imaging based on a Neurovascular Coupling) model, a unified EEG-fMRI source imaging framework that reconstructs cortical activity to simultaneously explain both modalities. FSINC integrates frequency-resolved EEG source activity with fMRI via a data-driven neurovascular coupling model that estimates band-specific coupling coefficients ({beta}) and accommodates a tunable spatial-temporal trade-off through hyperparameters ({lambda}2,{lambda} 3). In realistic simulations, FSINC outperformed conventional methods (wMNE, LORETA) in both spatial and temporal accuracy across EEG SNRs (-10 to 10dB) and numbers of concurrent sources (up to five), with optimal performance at{lambda} 2 = 102 and{lambda} 3=1 (e.g., LE: 0.51{+/-}0.24mm; SDI: 0.03{+/-}0.37mm; temporal accuracy: 0.95 {+/-} 0.05). Applied to simultaneous EEG-fMRI during contrast-reversing visual stimulation (=5.95Hz), FSINC revealed stimulus-locked responses localized to early visual cortex and stimulus-induced modulation of intrinsic alpha oscillations extending into visual and attention networks, patterns that conventional methods failed to capture. Estimated {beta}-weights were broadly consistent with prior reports of negative (theta/alpha) and positive (gamma) BOLD-electrophysiology associations. These findings demonstrate that FSINC enables high-spatiotemporal-resolution source imaging from EEG-fMRI recordings via data-driven hemodynamic modelling, and is expected to be well-suited for continuous and naturalistic brain states (e.g., resting state, natural moving-watching, and narrative listening) that are difficult to interrogate with either modality alone.

neuroscience↗

bioRxiv2026

Bicarbonate Efflux induces GABAergic Excitation and Seizures through pH Regulation

GABAergic signaling can paradoxically excite neurons and initiate seizures, but the underlying mechanisms remain unclear. We developed a computational model integrating pH regulation into neural dynamics to investigate GABAergic excitation. Our results show that GABA-induced bicarbonate efflux causes intracellular acidification and charge accumulation, which enhances neuronal excitability and can trigger seizure-like discharges through bifurcations in the neurodynamic system. Furthermore, we demonstrate that active pH-regulating transporters effectively counteract GABA-induced acidification to maintain neural stability. This work elucidates a novel pH-regulating mechanism for excitatory GABA responses, explaining how impaired pH regulation or excessive GABA stimulation may predispose neurons to seizures and suggesting new therapeutic targets for epilepsy.

neuroscience↗

bioRxiv2026

Hyperhomocysteinemia does not increase the risk of intracerebral hemorrhage in hypertensive mice

ObjectiveHyperhomocysteinemia (HHcy) affects approximately 75% of the population in China, and there is currently controversy regarding whether HHcy increases the risk of hemorrhagic stroke. This study aims to investigate the effects of high homocysteine (Hcy) levels on cerebral hemorrhage in hypertensive mice by administering homocysteine to them. MethodsMale C57BL/6 mice at 8 months of age were used in the experiment. The study was divided into two groups: the Hcy + AngII + L - NAME group and the AngII + L - NAME group. Magnetic resonance imaging (MRI) was performed when the mice exhibited signs of cerebral hemorrhage.After the hemorrhage, anesthesia was induced to euthanize the animals, and then the brain tissue was fixed. The total rearing period was 18 weeks. The relationship between homocysteine and stroke was described by plotting survival curves. The location and quantity of cerebral hemorrhage were determined through histopathological staining. ResultsThe serum Hcy concentration of mice fed with Hcy for 6 weeks increased to 23.07 mol/L, and the blood pressure ranged from 170 to 180 mmHg. The number of deaths due to cerebral hemorrhage was 10 in both the AngII + L - NAME + Hcy group and the AngII + L - NAME group. The p - value of the survival curves between the two groups was 0.162, indicating no statistically significant difference. ConclusionThe results demonstrated that elevated homocysteine levels did not influence the incidence of intracerebral hemorrhage in hypertensive mice. Hyperhomocysteinemia does not increase the risk of intracerebral hemorrhage in hypertensive mice

neuroscience↗

bioRxiv2026

IBDkb: an AI-enhanced integrative knowledge base for inflammatory bowel disease research and drug discovery

IBDkb (Inflammatory Bowel Disease Knowledge Base; https://www.biosino.org/ibdkb) is a freely accessible, integrated web-based platform that systematically curates and harmonizes multi-source data related to inflammatory bowel disease (IBD). To address the fragmentation and therapeutic gaps in existing specialized resources, IBDkb establishes a unified framework featuring advanced full-text search, interactive visualizations, cross-module knowledge graphs, and AI-powered utilities for real-time literature retrieval, trend analysis, text/PDF interpretation, and domain-specific conversational assistance. The platform currently integrates 98,453 research articles, 3,390 clinical trials, 200 investigational drugs, 200,606 bioactive compounds, 103 therapeutic targets, 77 experimental models, 12 pathogenesis summaries, and 15 treatment strategies. These integrated tools facilitate efficient exploration of complex associations among drugs, targets, trials, and mechanisms, thereby accelerating hypothesis generation and translational research in IBD. The platform is openly available without registration and supports data downloads. A case study on structure-aware drug comparison further demonstrates its utility in facilitating cross-disease drug repositioning hypotheses.

bioinformatics↗

bioRxiv2026

Calcium directs actin assembly via allosteric activation of formin INF2

Calcium signals spatiotemporally orchestrate cytoskeletal dynamics, typically through Rho GTPase-mediated signaling cascades, yet the direct molecular transducers that convert local calcium transients into spatially controlled actin assembly have remained elusive. Here, we uncover a structure-based mechanism by which calcium-bound calmodulin (Ca2+-CaM) directly activates formin INF2 to drive actin assembly. We demonstrate that Ca2+-CaM binds to the diaphanous inhibitory domain (DID) of INF2 with nanomolar affinity, inducing allosteric conformational changes that sterically disrupt INF2 autoinhibition. The unexpected bipartite Ca2+-CaM binding interface on INF2 enables ultrasensitive decoding of local calcium microdomains, such as ER-mitochondrial contacts, where activated INF2 promotes actin polymerization to facilitate mitochondrial fission. We further show that the Charcot-Marie-Tooth disease-associated INF2 R91G mutation enhances Ca2+-CaM binding via optimized interfacial dynamics, suggesting a gain-of-function disease mechanism. Our work establishes the Ca2+-CaM-INF2 axis as a direct molecular transducer linking spatial calcium signals to actin-dependent organelle dynamics, defining a Rho-GTPase-independent paradigm for calcium-cytoskeleton communication, with broad implications for INF2-linked pathologies.

biochemistry↗

bioRxiv2026

Transforming macromolecular structures into simulations of self-assembly

Macromolecular self-assembly is a fundamental process in living and engineered systems, producing molecular machines like the ribosome or highly symmetric viral capsids. Thanks to sources like the Protein Data Bank (PDB) and AlphaFold3, the final target complexes are often known, but these static structures do not provide information on the self-assembly process directly. Computational models provide critical tools to study these essential pathways of self-assembly, but substantial coarse-graining of assembly subunits is necessary to achieve computational tractability of these relatively slow processes while retaining multi-valency. While rule-based or local interactions overcome the often-prohibitive enumeration of all possible assembly intermediates, they must ensure global structural constraints are met. We here demonstrate ioNERDSS, a user-friendly Python package that transforms 3D atomic structures into coarse-grained models for immediate simulation with the stochastic reaction-diffusion NERDSS software, converting static structures into time-resolved assembly trajectories. NERDSS uses rule-based interactions to simulate multi-component self-assembly at the minutes timescales and without limits to complex size or growth pathways. With ioNERDSS, each protein chain is defined by a rigid subunit with discrete interfaces and explicit orientational constraints that enforce a structured assembly. Repeated subunits (such as in viral capsids) are regularized to preserve the target topology across distinct stochastic assembly pathways, supporting assembly of structures with thousands of subunits. We initialize pairwise binding affinities using open-source machine-learned prediction tools, and our default coarse-grained (CG) models are all constrained by thermodynamic reversibility to reach an equilibrium steady-state. The binding rates and subunit abundances necessary to perform simulations are initialized at default values but represent the key variables (along with affinities) that cells and thus users would tune to control productive assembly. Benchmarking on over 40,000 PDB structures shows that the majority of CG models stochastically assemble into target structures. The ioNERDSS Python library links directly to open-source tools for visualization and analysis to facilitate fast and user-friendly structure validation and analysis of output for thermodynamic, kinetic, and nonequilibrium drivers of macromolecular self-assembly.

biophysics↗

bioRxiv2026

GmEBS7a-E2 complex dissociation hyperactivates ERAD to impair plant immunity against Phytophthora pathogens

Endoplasmic reticulum-associated degradation (ERAD) pathways are crucial for maintaining plant development and stress responses. While ERAD has been extensively studied for its role in regulating responses to abiotic stress, its specific manipulation by eukaryotic pathogens stress remains unclear. Here, we reported that soybean GmEBS7a, a plant-specific ERAD component, is targeted and stabilized by a transmembrane domain-containing effector Avh131 from Phytophthora sojae. GmEBS7a enhances plant disease susceptibility by increasing ERAD efficiency and ER stress sensitivity. Mechanistically, Avh131 competitively disrupts the interaction with GmEBS7a and the ubiquitin-conjugating enzyme GmUBC32, reducing ubiquitination of GmEBS7a and subsequent inhibition of its degradation. These findings demonstrate that excessive ERAD triggered by stabilized GmEBS7a and its partnering E3 ligase impairs the plants response to biotic stress. Our study uncovers a fine-tuning of the ER protein-folding capacity to promote infection, thereby expanding our understanding of ER-centered immunity during plant-pathogen interactions.

immunology↗

bioRxiv2026

Structural and Evolutionary Divergence of the RAG1/1L N-Terminal Zinc-Finger Domain

RAG1/2 catalyzes V(D)J recombination to assemble antigen receptor genes, yet the zinc-finger element at the RAG1 N terminus has remained structurally and functionally uncharacterized. Using NMR spectroscopy, we determined the structure of the RAG1 N-terminal zinc-finger domain (NZD; residues 89-223). NZD adopts a compact, zinc-dependent fold comprising four -helices organized into two interdigitated zinc-finger modules, ZFa and ZFb. Structural similarity searches across protein-structure databases revealed no solved homologs, establishing NZD as a previously undescribed zinc-finger fold. Comparative analyses show that NZD is broadly conserved across RAG1 and RAG1-like (RAG1L) proteins but has undergone lineage-specific remodeling, including the jawed vertebrate-specific acquisition of an additional -helix (H2). Guided by structure prediction, we identified two NZD-like types in Chapaev transposases; one is highly similar to the RAG1L NZD, supporting an evolutionary link between RAG1/RAG1L and Chapaev NZDs. Similarity between ZFa and the single-zinc ZAD further suggests that NZD originated from an ancestral single-zinc fold. Together, these findings provide a structural framework for mechanistic and evolutionary analyses of RAG1.

biochemistry↗

bioRxiv2026

PRDX6 Modulates Immune Checkpoint Inhibitor Response by Antagonizing Ferroptosis Induced By HDAC Inhibitors

Therapeutic resistance limits the efficacy of histone deacetylase (HDAC) inhibitors and immune checkpoint therapies in cancer. While HDAC inhibitors can induce ferroptosis, tumor cells often evade this cell death via antioxidant defenses. Here we identify peroxiredoxin 6 (PRDX6) as a critical modulator of resistance to HDAC inhibitor largazole by suppressing ferroptosis through its phospholipase A2 activity and maintaining GPX4 expression. Using genome-wide CRISPR activation screening, biochemical assays, and syngeneic tumor models, we show that PRDX6 depletion enhances largazole-induced lipid peroxidation, ferroptotic stress, and reshapes the tumor microenvironment to promote T-cell infiltration and inflammatory cytokine release. Importantly, combining PRDX6 knockdown with HDAC inhibition potentiates anti-PD-L1 immunotherapy efficacy and prolongs survival in vivo. These findings reveal PRDX6 as a redox gatekeeper linking ferroptosis resistance to immune evasion and suggest that co-targeting PRDX6 and HDAC pathways may improve responses to cancer immunotherapy.

cancer biology↗

bioRxiv2026

Carbon dioxide sequestration into biomineral armor by ants

Over geologic time, Earths climate has been shaped by the capture and conversion of atmospheric carbon dioxide (CO2) into stable carbonate minerals, including dolomite [CaMg(CO3)2]. Accelerating natural carbon mineralization offers significant potential for mitigating anthropogenic climate change. Using stable carbon isotope tracking, nano-scale secondary ion mass spectroscopy, and 13C SSNMR, we show that, paralleling global biosphere-level processes, Sericomyrmex amabilis fungus-farming ants rapidly convert CO2 in their nest chambers into a biomineral layer covering their exoskeletons. We further reveal that biogenic carbon mineralization by these ants produces partially ordered dolomite. This rapid sequestration of CO2 into defensive armor in ants provides a fascinating natural example of mediation of potentially toxic accumulation of atmospheric CO2 that could inform human efforts to mitigate climate change.

ecology↗

bioRxiv2026

Choice of phenotype scale is critical in biobank-based GxE tests

The importance of gene-environment interactions (GxE) for complex human traits is heavily debated. Recently, biobank-based GWAS have revealed many statistically significant GxE signals, though most lack clear evidence of biological significance. Here, we partly explain this discrepancy by showing that many GxE signals simplify to additive effects on a different phenotype scale, a classical concern that is currently underappreciated. Our results clearly distinguish GxSex effects on height, which vanish on the log scale, from GxSex effects on testosterone, where the log scale uncovers biologically meaningful female-specific effects. Across 32 phenotypes in UK Biobank, we find that scaling by a power transformation can explain 46% of PGSxSex interactions, and that simple log transformation can explain 23%, with similar results for other environments. We also show that phenotype scale can substantially impact GWAS discovery and the construction and evaluation of polygenic scores. Finally, we provide a set of guidelines to consider and choose phenotype scale in modern genetic studies.

genetics↗