PLOS Genetics: New Articles

Correction: Doxifluridine promotes host longevity through bacterial metabolism

2026-11-03T14:00:00Z

by Rui Wei, Yuling Peng, Yamei Luo, Xinyuan Wang, Zhenzhong Pan, Ran Zhou, Huan Yang, Zongyao Huang, Yaojia Liu, Lunzhi Dai, Yuan Wang, Yan Zhang

Whole-proteome structure/function prediction in uropathogenic E. coli reveals previously missed host-microbe and microbe-phage interaction pathways

2026-11-03T14:00:00Z

by Chunxiang Peng, Henry Schreiber, Chengxin Zhang, Quancheng Liu, Scott Hultgren, Lydia Freddolino

The rapid advancement of high-throughput sequencing technologies has vastly increased the number of known protein sequences, but the experimental characterization of their structures and functions lags behind. This gap in knowledge impedes our understanding of biological mechanisms of these proteins, hinders the interpretation of high-throughput experiments, and exposes a significant challenge in modern biology: deducing the structural and functional information of proteins based on their sequences. Most computational approaches rely on homology with well-annotated proteins, yet many proteins lack identifiable homologues, reducing the power of this approach. Here, we integrated cutting-edge protein structure and function prediction methods to develop a complete sequence-structure-function pipeline that predicts structures and functions based on primary sequences. We applied this pipeline to predict the structure and function of all proteins in Escherichia coli UTI89, a model strain of uropathogenic E. coli. Based on the predicted functions, we performed enrichment analysis on the whole genome and revealed the possible roles and related biological mechanisms of poorly annotated proteins in this organism. Moreover, the performance of our pipeline was further validated through detailed case studies of the UTI89_C0931 and ybtS genes. Finally, we compiled the UTI89 structure and function database (https://seq2fun.dcmb.med.umich.edu/UTI89), offering it as a crucial resource to aid researchers in elucidating the roles of unannotated proteins. This database aims to bridge critical knowledge gaps in microbial pathogenicity and resistance, enhancing our capacity to tackle emerging health threats.

Adjusting for medication status in genome-wide association studies

2026-11-02T14:00:00Z

by Amanda H. W. Chong, Christopher Kintu, Yoonsu Cho, Segun Fatumo, Jason Torres, George Davey Smith, Tom R. Gaunt, Gibran Hemani

When conducting genome-wide association studies, addressing medication status that is relevant to the trait of interest can prevent biases that could distort estimates of the true genetic effect. Here, we introduce the genetic empirical medication reduction adjustment (GEMRA) method which uses a heuristic search for an empirical adjustment to be applied to phenotypic values of participants reporting medication use. Through simulations we show that the direct genetic effect estimates in the GEMRA approach exhibited less bias and greater statistical power than common strategies such as including medication as a covariate, restricting the sample to unmedicated users or including all samples without adjustment. We then applied the GEMRA approach to estimate statin medication adjustment for analysis of low-density lipoprotein (LDL) cholesterol levels and antihypertensive medication adjustment for analyses of systolic (SBP) and diastolic (DBP) blood pressure using multi-population data from UK Biobank and the Uganda Genome Resource. We found that a relative rather than an absolute adjustment better modelled the effect of medication on LDL cholesterol, SBP and DBP, with an effect of 40%, 10% and 10% reduction appearing to be consistent across populations, respectively. We also show that spurious differences in medication effects across populations can arise when the effect scale is misspecified.

Enhancing cell type deconvolution in spatial transcriptomics through incorporating multiple reference panels

2026-11-02T14:00:00Z

by Peiyao Zhao, Justin A. Colacino, Ying Ma, Xiang Zhou

Spatial transcriptomics (ST) captures gene expression with spatial context but often at resolutions where each spatial location contains multiple cells. Deconvolution of cell-type proportions is therefore essential, yet existing methods typically rely on a single scRNA-seq reference, limiting accuracy when references are incomplete or mismatched especially in complex tissues. These limitations highlight the need for a framework that can integrate multiple references while leveraging spatial information. We introduce SWIMR (Spatially Weighted Integration for Multi-Reference deconvolution), a statistical framework that integrates multiple scRNA-seq references while accounting for spatial correlations. SWIMR models each spatial location as a weighted combination of references, with both cell-type proportions and reference weights varying across tissue locations. Across comprehensive simulations and diverse ST datasets, SWIMR consistently outperformed single-reference approaches. In developing human heart tissue, it recovered ground-truth cell-type compositions with the highest accuracy. In human lung and breast cancer, SWIMR delineated tumor, stromal, and immune compartments, uncovered tumor-adjacent populations, and detected cell type–specific spatially variable genes missed by other methods. In mouse embryo and liver cancer, it leveraged context-specific references to resolve organ-specific cell types and increase sensitivity for biologically relevant pathways. Together, these results establish SWIMR as a robust framework for multi-reference deconvolution in spatial transcriptomics.

Genetic architecture of the murine serum metabolome reveals carboxyl esterases as master regulators of circulating fatty acid metabolism

2026-11-02T14:00:00Z

by Gregory R. Keele, Travis Nemkov, Ariel M. Hay, Matthew Vincent, Callan O'Connor, Daniel Stephenson, Grier P. Page, James C. Zimring, Gary A. Churchill, Angelo D’Alessandro

Background

The systemic biochemical diversity of circulating metabolites and lipids reflects the integrated effects of genetic variation and environmental exposure. Metabolite quantitative trait locus (mQTL) studies in humans have established gene-metabolite associations, but genetic contributions can be obscured by sex, diet, age, medication use, and environmental exposures. Genetically diverse model systems offer a powerful complementary strategy to isolate genetic contributions to the biochemical diversity of the circulating metabolome.

Methodology/Principal findings

We applied mass spectrometry profiling to serum samples in 541 mice from the Diversity Outbred (DO) population and identified 1,933 mQTL across 240 metabolites, 561 lipids, 43 oxylipins, and 4,465 MS/MS features. QTL hotspots on chromosomes 8, 9, 10, and 17 implicated distinct loci in the regulation of serum lipids, metabolites, and peptide-like features. The chromosome 8 Ces1 and Ces2 gene clusters were associated with lipids, acylcarnitines, and acyl-CoAs, while chromosome 9 and 10 loci included additional lipid and metabolite QTL. On chromosome 17, MHC and C3 regions were associated with untargeted peptide-like MS/MS features. Comparisons with matched red blood cell mQTL revealed widespread compartment-specific genetic control.

Conclusions/Significance

Collectively, these findings provide a high-resolution map of the genetic regulation of the circulating metabolome, offering mechanistic insights that complement and extend human metabolic genetics.

A common pathogenic founder variant in Rwandan breast cancer cases

2026-11-02T14:00:00Z

by Achille V. C. Manirakiza, Shakuntala Baichoo, Annette Uwineza, Damas Dukundane, Eulade Rugengamanzi, Janviere Mutamuliza, Allison M. O. Niragira, Raissa Muvunyi, Jeffrey Besada, Sarah M. Nielsen, Brianna Bucknor, Diane R. Koeller, Caroline Andrews, Leon Mutesa, Temidayo Fadelu, Timothy R. Rebbeck

Germline data from African populations remain sparse, limiting characterization of population-specific BRCA1/2 pathogenic variants (PV). In a study of 175 Rwandan women with breast cancer, 7 unrelated carriers (4% of cases; 22% of PV carriers) harbored the same BRCA1 frameshift PVs, c.4065_4068del (p.Asn1355Lysfs*10), which is extremely rare in gnomAD yet recurrent in European, Asian, and Middle Eastern cohorts. Whole-exome sequencing and haplotype analysis of all 7 carriers revealed a shared ancestral block of approximately 581 kb surrounding the variant, and extended haplotype homozygosity and network analyses confirmed a common founder origin. Coalescent-based age estimation placed the founder event approximately 4,000--10,000 years ago. Comparison with 1000 Genomes Project data showed the founder haplotype is absent or exceedingly rare outside African and South Asian populations. These findings strongly suggest the c.4065_4068del variant as a pre-historical BRCA1 founder variant in Rwanda, with implications for targeted genetic testing, cascade screening, and cancer prevention in the region.

Conditional-prevalence correction for liability-scale analyses of covariate-adjusted binary GWAS

2026-10-30T14:00:00Z

by Siyi Chen

Adjustment for heritable covariates in genome-wide association studies of disease can induce collider bias, creating spurious genetic associations. Following bias correction, interpretation on the liability scale, which represents continuous disease susceptibility, requires an appropriate conversion from log odds. We derive this conversion under a Gaussian liability model for small genetic effects. The direct effect, excluding pathways through the adjusted covariates, and the collider-bias component share a common conversion factor. We characterize how this factor depends on variation in disease risk across covariate values and extend the derivation to case-control sampling. In simulations, the proposed conversion reduced the effect-size inflation associated with scaling based solely on disease prevalence. These results link existing collider-bias corrections to estimation of direct liability effects and clarify the interpretation of covariate-adjusted associations in population and case-control studies.

kri-1/KRIT1 promotes innate immune and lipid homeostasis in the C. elegans intestine

2026-10-30T14:00:00Z

by Akshay Alaghatta, Samantha Y. Tse-Kang, Daniel Bollen, Khursheed A. Wani, Nicholas D. Peterson, Read Pukkila-Worley

Animals must differentially allocate essential metabolic resources in response to changing environmental conditions to ensure reproductive success. For example, adult C. elegans coordinate innate immune defenses during infection and also allocate fat stores to the germline, each of which are required for evolutionary fitness. The genetic mechanisms that integrate resource allocation and host defenses in this context, however, are not fully understood. From a forward genetic screen for novel regulators of innate immune gene transcription, we identified kri-1, the nematode homolog of human Krev interaction trapped protein KRIT1. Mutations in human KRIT1 underlie cerebral cavernous malformations, a disease marked by defects in vascular integrity. Similarly, C. elegans kri-1/KRIT1 is required for the integrity of the intestinal epithelial cell barrier. We find also that kri-1/KRIT1 is required for host tolerance to bacterial infection, fecundity, and normal development. In this context, kri-1/KRIT1 restrains the activity of the cytoprotective transcription factor skn-1/NRF2 to control immune gene transcription and likely intestinal lipid mobilization during aging, a process necessary for healthy reproduction, but functions independently of skn-1/NRF2 to promote epithelial integrity and pathogen tolerance. These data reveal a broad role for a strongly conserved regulator in essential physiological processes that are required for reproductive fidelity and evolutionary success.

Nicotinic receptor in dopamine neurons mediates learned odor choice

2026-10-29T14:00:00Z

by Nobuhiro Yamagata, Nobuhiro Takahashi, Rino Ichikawa, Eru Wada, Momo Murakami, Ayako Abe, Mai Kanno, Toshiharu Ichinose, Norihiro Katayama, Hiromu Tanimoto

Nicotinic acetylcholine signaling modulates dopaminergic output in mammalian midbrain circuits and can thereby influence decision-making. In Drosophila, dopamine neurons (DANs) in the protocerebral anterior medial (PAM) cluster convey sugar reward signals and promote approach toward a rewarded odor after associative learning. Although nicotinic acetylcholine receptors (nAChRs) have been implicated in regulating PAM DAN excitability and transmitter release, how this modulation supports specific cognitive operations during learning and memory remains unclear. Here, we tested the role of nAChRs in PAM DANs in odor–sugar associative learning and memory. Among nine nAChR genes examined, loss of the nicotinic acetylcholine receptor α1 subunit (Dα1) in PAM neurons impaired appetitive memory. Consistent with this requirement, Dα1 was detected in these DANs at both the transcript and protein levels, with Dα1 puncta observed in PAM axon-terminal and putative dendritic regions. Importantly, live imaging showed that Dα1 knockdown in PAM DANs attenuated odor-evoked synaptic Caa²⁺ signals, whereas sugar-evoked Ca²⁺ responses were largely preserved. Behaviorally, Dα1 knockdown in PAM DANs reduced performance in a two-odor forced-choice discrimination task, whereas no performance deficit was detected across the single-odor pursuit conditions or innate odor choice. Together, these results identify a nicotinic mechanism in PAM DANs that supports odor-evoked synaptic activity and contributes to learned odor-choice performance when competing odor cues are present.

The lipid raft marker flotillin FloA drives relocalization of the plasma membrane H⁺-ATPase PmaA as a protective response to calcium stress

2026-10-29T14:00:00Z

by Moemi Kawashima, Thomas Krüger, Maira Rosin, Sophie Tröger-Görler, Thorsten Heinekamp, Axel A. Brakhage

Biological membranes are laterally heterogeneous and contain specialized microdomains called lipid rafts. Lipid rafts serve as organizational platforms that cluster signaling molecules or modulate membrane protein conformation through their unique lipid environment. There are specific lipid raft marker proteins whose functions remain obscure. One of these proteins is flotillin which has been linked to endocytosis. Here, we investigated the regulation and function of FloA, the sole flotillin homolog in the model fungus Aspergillus nidulans. FloA expression is specifically upregulated in response to calcium stress, which is a regulatory pattern also conserved in Aspergillus fumigatus. BioID proximity labeling revealed that A. nidulans FloA physically interacts with proteins in the endocytic pathway as well as another lipid raft marker, the plasma membrane H⁺-ATPase PmaA. Under calcium stress, PmaA undergoes internalization from the cytoplasmic membrane. However, when floA is deleted, PmaA internalization is prevented, resulting in cell death. This phenotype of the ΔfloA strain could be mimicked by treating the cells with an endocytosis inhibitor during calcium stress. Together, we demonstrate that FloA is essential for the internalization of PmaA during calcium stress, a process that prevents intracellular calcium overload and promotes cell viability. Our results also provide further evidence for flotillin-assisted endocytosis.

Recombination rate and efficiency of linked selection in small and large stickleback populations

2026-10-28T14:00:00Z

by Hongbo Wang, Chaowei Zhang, Kerry Reid, Juha Merilä

Population genetic theory predicts that natural selection will be more efficient in large than small populations because genetic drift reduces the efficiency of selection in small populations. Small populations adapting to new environments can also be expected to evolve higher recombination rates to facilitate adaptation as well as to dissociate and purge harmful mutations. We tested these hypotheses (1) by investigating differences in the strength of association between nucleotide diversity (π) and recombination rate across the genomes of nine-spined sticklebacks (Pungitius pungitius) from four small freshwater (mean N_e ≈ 7 096) and four large marine (mean N_e = 376 828) populations, as well as (2) by comparing recombination rates between small and large populations using population specific linkage maps. We found the predicted positive correlation of π with recombination rate from all but the smallest freshwater populations, suggesting prevalent linked selection even after accounting for variation in GC/CpG content, and gene density. Mean recombination rates did not differ between freshwater and marine populations, except that the smallest N_e freshwater population exhibited significantly elevated recombination rate. Exploratory GWAS analyses suggested a possible polygenic basis for recombination rate. These results suggest an important role for linked selection in reducing π in low recombination regions especially in large populations. Moreover, as predicted by theory, at least one of the small freshwater populations appears to have evolved a higher recombination rate than its marine ancestors.

Fast probabilistic whitening transformation for ultra-high dimensional genetic data

2026-10-28T14:00:00Z

by Gabriel E. Hoffman, Christian P. Dillard, Kiran Girdhar, Panos Roussos

Statistical methods often make assumptions about independence between the samples or features of a dataset, yet correlation structure is ubiquitous in real data. In statistical genetics, correlation between regression summary statistics due to linkage disequilibrium (LD) between nearby variants complicates downstream analysis. Many methods use LD reference panels to account for this correlation. Whitening transformations comprise a family of methods to remove correlation structure, and are used implicitly by many common models. Here we propose a probabilistic model for data whitening, and propose parameter estimates and efficient algorithms to improve statistical and computational performance. In an application to impute z-statistics from unobserved genetic variants from a genome-wide association study of schizophrenia, the probabilistic whitening transformation, had the lowest mean square error while being up to an order of magnitude faster than other methods. Using this approach, we also identify tandem repeats that explain genetic regulatory signals for disease-relevant genes. Analyses are implemented in our novel open source R packages decorrelate and imputez.

CDH1 loss remodels gene expression and lineage identity in human mammary epithelial cells

2026-10-27T14:00:00Z

by Maggie Musick, Chinasa A. Ufondu, Carmen E. Rowland, Micaela E. Brown, Joseph L. Sottnik, Madeleine T. Shackleford, Camryn S. Nesiba, Etienne P. Danis, Andrew E. Goodspeed, Richard Zera, Arthur T. Johnson, Kathryn L. Schwertfeger, Andrew C. Nelson, Julie H. Ostrander, Matthew J. Sikora

Invasive lobular carcinoma (ILC) is a common subtype of breast cancer, molecularly defined by genetic loss of CDH1, and subsequent loss of cell adhesion protein E-cadherin, in ~95% of ILC. Though CDH1 loss occurs early in ILC oncogenesis, it is unclear how this facilitates transformation. We modeled early CDH1 loss using “normal” human mammary epithelial cells (HMEC), i.e., finite lifespan cells reflecting early hyperplasia, and targeted E-cadherin signaling using antibodies versus causing genetic CDH1 loss using siRNA or CRISPR/Cas9-knockout. Transcriptome analysis across four HMEC models showed that the mode of E-cadherin targeting is critical for the subsequent phenotype. Antibody-mediated inhibition of cell-cell contacts induced gene signatures of epithelial-mesenchymal transition (EMT), consistent with the role of E-cadherin suppression during the EMT process. Conversely, genetic CDH1 loss – as in ILC oncogenesis – repressed EMT signatures, and instead remodeled gene expression toward a luminal epithelial phenotype. RNA-seq, single cell transcriptomics, flow cytometry, microscopy, and ATAC-seq analyses support that CDH1 loss induces lineage remodeling to a luminal state, which is mirrored in transcriptomic analysis of clinical ILC precursor lesions. By isolating luminal versus basal cells prior to CDH1 knockout, we found that CDH1 loss led to remodeling of lineage identity in both populations, converging on a new lineage homeostasis with a luminal progenitor-like phenotype. Consistent with the shift to a luminal progenitor phenotype, CDH1 loss enhanced proliferative capacity over the finite lifespan of the HMECs, highlighting a feature of early CDH1 loss that may contribute to clonal advantage during tumor initiation. Moreover, CDH1 loss enhanced anoikis resistance, a defining feature of ILC cells. Our findings support that genetic loss of CDH1 in mammary epithelial cells induces transcriptional and phenotypic changes consistent with lineage identity remodeling toward a luminal progenitor-like state, which may underpin the mechanism by which early CDH1 loss mediates ILC oncogenesis.

The peculiar properties of pericentromeric regions of genomes and their influence on sex chromosome evolution

2026-10-27T14:00:00Z

by Deborah Charlesworth

Results from recent genome sequences support the idea that the lack of recombination across extensive sex-linked regions (SLRs) in some species may be a pre-existing feature, due mainly to the sex-determining locus being located near a centromere. This would cause it to be affected by the “centromere-effect”, which ensures low recombination rates near centromeres. In such cases, it is unnecessary to invoke any active recombination suppression process, or to debate ideas about the types of selection involved. In this review, I outline the properties of genome regions that recombine rarely, including pericentromeric regions of chromosomes, and discuss SLRs that overlap with pericentromeric regions. Unsurprisingly, it is difficult to distinguish special features of such SLRs that would suggest they have undergone a recombination suppression process. The property most likely to be specific to completely SLRs is major gene loss from Y- or W-linked regions of genes found in their respective X- or Z-linked counterparts, and this asymmetry is observed in many species. However, if pericentromeric regions are characterised by ephemeral gene content and low gene expression, asymmetry between pericentromeric SLRs might be less pronounced than in SLRs in other genome regions, and similar Y and X degeneration levels are indeed documented in several species. Additionally, some such SLRs may not be completely sex-linked, which could explain findings of extensive SLRs with low Y-X (or W-Z) divergence.

Auxilin in enteroendocrine cells controls intestinal homeostasis through inter-cell signaling relays

2026-10-26T14:00:00Z

by Runqi Wang, Zhengran Li, Jing Wei, Jiajia Wang, Xiyue Liu Tao, Danjie Zhang, Ruiyan Kong, Xuejing Ren, Hang Zhao, Zhouhua Li

Adult stem cells are critical for the homeostasis of residential tissue and organism fitness. Residential stem cells must constantly perceive external and internal signals and adjust their proliferation rate accordingly to avoid unlimited proliferation or premature differentiation. However, how differentiated cells affect stem cell proliferation and tissue homeostasis through cell-cell communication still remains poorly understood. Here, we unveil an unprecedented function of Auxilin (Aux) in enteroendocrine cells (EEs) by restricting intestinal stem cell (ISC) proliferation. aux depletion in all EEs leads to intestinal homeostasis disruption. The levels of Slit are dramatically reduced in aux-depleted EEs and cytokine Upd3 expression is significantly increased in some aux-depleted EEs and neighboring wild type enterocytes (ECs). Ectopic expression of slit could effectively rescue the defects observed in pros^ts > aux^RNAi intestines. Interestingly, EGFR signaling is ectopically activated due to EGFR accumulation in aux-depleted EEs. Further inhibiting EGFR signaling completely suppresses the defects in pros^ts > aux^RNAi intestines. Finally, EGFR signaling suppresses slit transcription by Pointed binding to slit regulatory regions. Together, these data show that Aux in EEs restrains ISCs from excessive proliferation and aberrant progeny differentiation to maintain intestinal homeostasis through inter-cell communications. Thus our study uncovers the underlying mechanism of how stem cell proliferation is properly controlled by differentiated cells through inter-cell signaling relays during tissue homeostasis and tumorigenesis.

Extensive mobilome heterogeneity in a widespread endosymbiont: A candidate dimeric plasmid and highly fragmented prophages in Wolbachia from Culex pipiens

2026-10-26T14:00:00Z

by Alice Brunner, Maxime Mahout, Julien Amoros, Massilva Rahmoun, Mateo Jarry, Seth R. Bordenstein, Sarah R. Bordenstein, Blandine Trouche, Julie Reveillaud

The obligate, intracellular bacteria Wolbachia have gained increasing interest due to their selfish modifications of host arthropod reproduction, impacts on host evolution, and utility in vector control efforts to reduce arbovirus transmission worldwide. Despite their highly reduced genomes, Wolbachia harbor a rich mobilome that includes phages, insertion sequences and plasmids in mosquito vectors. However, these repeat-rich mobile genetic elements are notoriously difficult to assemble and can generate artificial, chimeric sequences that obscure their true diversity. As a result, conventional genome sequencing and assembly approaches often fail to resolve the complexity, leaving critical gaps of knowledge on how these elements evolve, mobilize, and shape both symbiont and host genomes. To address these challenges, we established a novel Oxford Nanopore long-read sequencing strategy that avoids prior PCR amplification and leverages single-dissected, female ovaries. Using this approach, we report and characterize—directly from native long-read molecules—the first near-complete Wolbachia genome and its mobile elements from individual ovaries of the mosquito vector Culex pipiens molestus. Additional short reads from individuals of the same strain were used to assess and validate candidate mutations, particularly in repetitive regions. We report a new dimeric structure of the pWCP plasmid, suggesting the existence of multimeric plasmid forms potentially associated with active replication. We also observed extensive fragmentation of prophage WO regions despite long read sequencing, underscoring their structural complexity. Raw long read analyses recovered multiple alternative gene syntenies within WO regions, pointing to heterogeneous prophage architectures missed by the assembly and marked diversity of WO elements in Wolbachia of Culex pipiens (wPip) group strains. Taken together, our results illuminate the structural heterogeneity of the endosymbiont genome that is shaped by integrated and episomal mobile elements.

Distinct core minor pilin complexes prime specialized type IV filaments in cyanobacteria

2026-10-26T14:00:00Z

by Nils Schuergers, Lars Wittig, Gen Enomoto, Julia Herz, Shamphavi Sivabalasarma, Katharina Ruoff, Friedel Drepper, Sonja-Verena Albers, Pitter F. Huesgen, Annegret Wilde

The model cyanobacterium, Synechocystis sp. PCC 6803 encodes in addition to the major pilin of the Type IV pilus filament, an extensive, partially uncharacterized repertoire of minor pilins. For those cyanobacterial minor pilins that have been characterized, their roles span a surprisingly diverse range of functions. To elucidate the roles of uncharacterized minor pilins in a systematic way, we applied structural phylogenomics across 90 genomes, classifying cyanobacterial pilins into six conserved families that form two distinct putative core priming complexes. We demonstrate that these complexes initiate the assembly of two morphologically distinct Type IV pilus filaments: short, hyper-dynamic pili for natural competence, and long, adhesive pili for motility and phototaxis. Structural analysis revealed a conserved beta-solenoid domain in PilX subunits, which we propose fulfills the capping function of PilY1 homologs. Proteomic data indicate that the minor pilin PilX2 facilitates the assembly of motility pili, which is required to maintain DnaJ3 co-chaperone levels and trigger cAMP-dependent surface sensing. These findings challenge the concept of a single multipurpose pilus, establishing that cyanobacteria utilize a shared machinery to assemble two specialized filaments, each primed by distinct core minor pilin complexes to meet the conflicting biophysical requirements of DNA uptake and surface motility.

Multi-omics analysis of high-grade serous ovarian cancers reveals heterogeneity and distinct immunological patterns based upon clinico-genomic status

2026-10-22T14:00:00Z

by Jing Qian, Rania Bassiouni, Yuxin Jin, Seeta Rajpara, Monica Neuman, Varun U. Khetan, Bodour Salhia, David W. Craig, Joseph W. Carlson, Lynda D. Roman, John D. Carpten

High-grade serous ovarian cancer (HGSOC) is characterized by remarkable intratumoral heterogeneity and variable tissue architectures, dictating differential therapeutic responses. Although BRCA1/2 mutations correlate with improved responses to DNA-damaging agents, how BRCA genotype shapes the tumor immune microenvironment (TIME) remains incompletely understood. Here, we integrated whole exome sequencing, total RNA sequencing and spatial transcriptomics to profile a cohort of BRCA-mutated (BRCA-MT) and non-BRCA-mutated (BRCA-WT) HGSOC tumors. While bulk transcriptomics highlighted global phenotypic shifts, suggesting a more pro-inflammatory milieu in BRCA-MT tumors, spatially resolved analysis revealed how these differences manifest within specific tissue architectures. Integrated clustering revealed recurrent spatial transcriptional states across genotypes. Specifically, we identified a transcriptionally distinct immune-enriched region (IC7) characterized by low tumor purity, interferon signaling, and antigen-presentation programs. Reference-based RCTD deconvolution provided orthogonal computational support that IC7 was enriched for T/NK and dendritic cells relative to non-IC7 regions. At the patient level, the functional state of IC7 was highly BRCA-dependent: BRCA-MT tumors exhibited stronger enrichment of interferon-α/γ responses and inflammatory signaling than BRCA-WT tumors. Exploratory CellChat analysis further suggested genotype-associated differences in predicted immune-related signaling. We also identify a conserved structural interface between CAF-like region (IC3) and macrophage-rich region (IC4), accompanied by a predicted CXCL12–CXCR4 chemokine recruitment axis. Taken together, these findings support a model in which BRCA mutation status is associated with functional differences within broadly conserved spatial regions, rather than extensive reorganization of the overall spatial architecture. This spatially resolved framework identifies BRCA-associated immune transcriptional patterns in HGSOC and provides a basis for future mechanistic validation.

Meta-analysis of over 8,000 individuals from Hawai‘i and Samoa for genetic associations to cardiometabolic phenotypes

2026-10-21T14:00:00Z

by Bryan L. Dinh, Xinran Wang, Xin Sheng, Peggy Wan, Amit Kumar Srivastava, Take Naseri, Satupa‘itea Viali, The Samoan Obesity, Lifestyle and Genetic Adaptations (OLaGA) Study Group , Lynne R. Wilkens, Loïc Le Marchand, Christopher A. Haiman, Daniel E. Weeks, Charleston W. K. Chiang, Jenna C. Carlson

Although genome-wide association studies (GWAS) now routinely reveal genetic associations and biological insights in millions of individuals, underrepresentation of global populations, such as those from Polynesia, continue to persist. These exclusions, often driven by logistical challenges and lack of data, prevent systematic identification of population-enriched associations, such as the association of the missense variant at the CREBRF locus to BMI and type 2 diabetes discovered commonly occurring in Polynesian populations due to its rarity in global populations. Armed with the recently updated TOPMed imputation panel that could benefit studies in diverse populations that previously had poorer imputation performance, we performed the first GWAS of Native Hawaiians and Samoans, the largest to date of Polynesian-ancestry populations (combined N up to 8,461) to identify population-enriched associations for 13 adiposity and cardiometabolic traits available across both cohorts: BMI, fasting glucose, fasting insulin, HDL, height, hip circumference, HOMA-IR, LDL, T2D, total cholesterol, triglycerides, waist circumference, and waist-hip ratio. We found 25 trait-loci associations that met genome-wide significance: 20 previously reported or known associations and 5 putatively new associations via meta-analysis. In particular, with improved statistical power, we were able to confirm the previously suggestive association between the missense CREBRF variant with fasting glucose levels. The remaining 4 potentially novel loci-trait associations for BMI, LDL, and waist-hip ratio, however, were not replicated in All-of-Us. The lack of Polynesian-enriched findings outside of the CREBRF locus informs the bounds of the effect sizes or frequencies of any enriched variants and suggests that further expansion of cohort sizes from this region of the world and improved imputation references specific to these populations are needed to identify more population-enriched associations.

The role of gene regulatory evolution in weapon diversification: Insights from comparative genomics, chromatin profiling, and functional analyses of BMP signaling in horned beetles

2026-10-21T14:00:00Z

by Phillip L. Davidson, Isabel G. Manley, Armin P. Moczek

Condition-responsive growth is a common feature of multicellular development, during which organisms integrate genetic and environmental signals to adjust their phenotype. However, the molecular properties shaping condition-responsive diversification remain poorly understood. The beetle genus Onthophagus offers promising opportunities to investigate this question, given its diversity of sex- and nutrition-responsive phenotypes, including horns — novel, secondary sexual weapons used in reproductive competition. We compared the gene regulatory properties of horns in two closely related species exhibiting highly specialized sex- and nutrition-biased phenotypes. We found a dynamic cis-regulatory landscape in developing horn tissue, shaped by mutational accumulation across species, condition-specific changes in chromatin accessibility within species, and the acquisition of lineage-specific regulatory elements. Many of these putative regulatory regions include binding site motifs of critical developmental regulatory genes, including members of the bone morphogenetic protein signaling pathway. We provide functional evidence that two proteins in this pathway have been co-opted for horn development, influencing the shape and size of this trait across species, sexes, and nutritional states. These findings provide evidence that evolutionarily labile cis-regulatory interactions may evolve alongside diversification of condition-specific traits, potentially modifying the activity of conserved developmental pathways over short evolutionary timescales.

NLGN3 autism variants have distinct functional impact on synapses and sleep behavior in Drosophila

2026-10-16T14:00:00Z

by Rebekah E. Townsley, Jonathan C. Andrews, Saurabh Srivastav, Sharayu V. Jangam, Shabab B. Hannan, Oguz Kanca, Paul C. Marcogliese, Shinya Yamamoto, Michael F. Wangler

Neuroligin-3 (NLGN3) was first identified as a X-linked risk gene associated with autism spectrum disorder (ASD). Most reported variants are identified in males who inherited their variants from an unaffected mother, but de novo variants have also been identified in both affected heterozygous females and hemizygous males. The p.R451C variant was the initial variant associating NLGN3 with ASD and has been heavily investigated, yet little is known about the functional consequences of other NLGN3 variants. To determine the functional consequences of other NLGN3 variants in vivo, we generated transgenic Drosophila models corresponding to a de novo variant (p.R175W) identified in a heterozygous female proband with ASD, a maternally inherited variant (p.R451C) identified in a hemizygous male with ASD, and another maternally inherited variant identified in a male (p.R597W) associated with sleep disorder and ASD. In Drosophila, loss of the fly homolog, Nlg3, altered sleep patterns, synaptic architecture, and vesicle dynamics, which were rescued by the expression of the human NLGN3^Ref allele. When comparing the variants, the p.R175W variant and the maternally inherited p.R451C variant altered synapse morphology with minimal effects on vesicle dynamics, and the p.R597W variant altered sleep and vesicle dynamics with minimal impact on synapse morphology. Using overexpression models, human NLGN3^Ref altered sleep patterns and synaptic morphology. Moreover, the p.R175W variant exacerbated sleep phenotypes, and the p.R175W and p.R451C variants exacerbated synapse morphology phenotypes. Together, our findings suggest that the de novo NLGN3 p.R175W variant identified in a heterozygous female exhibits gain-of-function properties, while maternally inherited variants have context-dependent functional impact. Moreover, some NLGN3 variants disrupt synaptic development, while other variants alter synaptic function, suggesting that NLGN3 variants have differential effects. These functional differences may provide insight into the heterogeneity of individuals with ASD.

Revisiting the impact of synthetic ORF sequences on engineered LINE-1 retrotransposition

2026-10-16T14:00:00Z

by Dorothy Chan, Stephanie Workman, Nathan Smits, Alexander L. Carleton, Patricia Gerdes, Jeffrey S. Han, Jef D. Boeke, Geoffrey J. Faulkner, Sandra R. Richardson

The retrotransposon Long Interspersed Element-1 (L1) contains adenosine rich open reading frames (ORFs), a characteristic that limits its expression in mammalian cells. A synthetic mouse L1 (smL1) with ORF adenosine content decreased from 40% to 26% showed increased mRNA expression and retrotransposed far more efficiently than the native parental element, L1spa (1). Here, we observe two nonsynonymous substitutions between the L1spa and smL1 ORF1 sequences and note that the smL1 3’UTR lacks a conserved guanosine-rich region (GRR) which could take on a G-quadruplex secondary structure. We find that the combined effect of the altered ORF1p amino acid sequence and the GRR 3’UTR deletion, rather than synthetic ORF sequences, accounts for the increase in smL1 retrotransposition efficiency over L1spa. We determine that inclusion of the GRR influences natural mouse L1 retrotransposition in a position-dependent manner that does not involve premature polyadenylation of L1 mRNA transcripts or alteration of L1 insertion structures. Instead, we present evidence that the position-dependent effect of the GRR on natural mouse retrotransposition occurs through modulation of L1 ORF1p abundance. In contrast, smL1 retrotransposition is refractory to the inhibitory effect of the GRR, likely owing to highly efficient protein expression from synthetic ORF sequences. Taken together, our results prompt further investigation of the relationship between the GRR sequence and L1 protein expression and demonstrate that the arrangement of L1 nucleotide sequences within reporter constructs can influence L1 expression and engineered retrotransposition efficiency.

Genome-Wide DNA methylation profiling of tissue-plasma pairs identifies Novel cfDNA biomarkers for the diagnosis of gastric cancer

2026-10-15T14:00:00Z

by Hailing Ou, Jinli Miao, Fusheng Ling, Jie Gao, Tingan Wang, Zhihua Ye, Chunbo Zhang, Mingwei Huang, Yuzhou Qin

Screening for gastric cancer (GC) is critical for improving patient survival, yet current clinical methods suffer from invasiveness and limited sensitivity. The aim of this study is to develop a machine learning model for the non-invasive diagnosis of GC using the whole-genome methylation profile of circulating free DNA (cfDNA) in plasma. Plasma cfDNA from 61 patients with GC and 29 healthy controls. First, whole‑genome bisulfite sequencing (WGBS) was performed on 29 paired GC and adjacent normal tissues to identify differentially methylated regions (DMRs). These tissue DMRs were then mapped to plasma cfDNA methylation data, yielding 32 stable DMRs that changed consistently in both tissues and plasma. Using LASSO and Random Forest (RF) algorithms, eight core diagnostic markers were selected. Four machine learning algorithms (Support Vector Machine, RF, K-Nearest Neighbor, Naïve Bayes) were used to build diagnostic models. WGBS revealed global hypomethylation and CpG island hypermethylation in GC, consistent with plasma cfDNA methylation patterns. The RF model built on the eight cfDNA methylation markers (annotated to genes including ATP8A2) performed best, achieving AUC values of 0.978 and 0.938 in the training and independent test sets, respectively, with an accuracy of 88.46%, sensitivity of 94.44%, and specificity of 75.00%. After adjusting for age, the model achieved an AUC of 0.924 on the test set, still demonstrating high discriminatory performance. Functional analysis implicated these markers in pathways such as phagocytosis and axon guidance, and showed significant correlation with immune cell infiltration. Notably, these core DMRs are not covered by the probes on the methylation arrays (450K and EPIC v2), highlighting the advantage of WGBS for novel biomarker discovery. In conclusion, tissue-plasma concordance analysis identified a panel of plasma cfDNA methylation biomarkers with strong diagnostic potential. The resulting RF model provides a promising non-invasive strategy for GC screening.

Diversification and functional expansion of archaeal T4F machineries

2026-10-14T14:00:00Z

by Shamphavi Sivabalasarma, Sonja-Verena Albers

Archaea have several cell surface structures belonging to the type 4 filament (T4F) superfamily. All share a minimal core assembly system consisting of an ATPase, a platform protein, a filament-forming protein, and a class III signal peptidase. Here, we generated novel MacSyFinder2 models to identify and classify archaeal T4F systems. Our analysis revealed a vast diversity of archaeal T4F, with many organisms harboring one or more assembly machineries. Structure-based phylogenetic analysis showed that the variable N-terminal domain of T4F-related ATPases mirrors the subsystem clustering, indicating that the core machinery has diversified within the archaeal secretion ATPase family through structural innovation. Genome-wide screening for signal peptidase III cleavage site (SPIII) containing proteins revealed the widespread presence of substrate-binding proteins carrying a class III signal peptide. We propose that these binding proteins, with canonical SPIII cleavage sites, functionalize T4F machineries for efficient substrate scavenging, expanding the functional repertoire of archaeal T4F systems beyond their currently characterized roles.

The AF-2 domain of estrogen-related receptor interacts with PPRC1 to modulate larval epidermal marking in Bombyx mori

2026-10-12T14:00:00Z

by Jinxin Wu, Die Liu, Haoran Xu, Lingqing Zeng, Ping Lin, Ping Zhao, Guanwang Shen

Estrogen-related receptors (ERRs) have no natural ligands, vertebrate ERRs rely on their activation function-2 (AF-2) structural domain to recruit coactivators for transcriptional regulation. While metabolic regulation in insects differs significantly from that in vertebrates, it remains unclear whether the regulatory function of insect ERR requires coactivators. Using silkworms as the research subject, this study aims to analyze the molecular mechanisms of ERR-regulated metabolism in insects and refine the metabolic regulatory network. This study applied CRISPR/Cas9 gene editing technology to knock out the AF-2 domain of BmERR in the lepidopteran silkworms and examined its effects on functional role, associated interacting factors, and related physiological processes. Disruption of the BmERR AF-2 domain inhibited the expression of melanin metabolism-related genes BmTH, BmDDC, BmAA-NAT, Bmebony, and Bmtan, leading to the accumulation of tyrosine and dopa, thereby causing aberrant melanin metabolism and loss of epidermal markings. By contrast, BmERR overexpression enhanced the pathway, resulting in intensification of epidermal markings. The homologous gene of the ERR coactivator, BmPPRC1, showed highly consistent expression with BmERR in the epidermis. The immunofluorescence signal of BmPPRC1 was localized to the nucleus and highly overlapped with that of BmERR. BmPPRC1 interacts with the AF-2 domain of BmERR, and deletion of this region weakens the regulation of melanin metabolism-related genes in silkworm embryonic cells. The ERR function and mode of action are evolutionarily conserved, and its AF-2 structural domain binds equally well to the coactivator BmPPRC1, providing new perspectives for studying the modulability of insect mottle formation.

An NKX2-3/5/6 homolog is required downstream of BMP signaling to pattern the sensory-adhesive organ of a tunicate larva

2026-10-12T14:00:00Z

by Christopher J. Johnson, Joshua Kavaler, Timethea Slade, Kayla Wilson, Christina D. Cota, Alberto Stolfi

Tunicates are the sister group to vertebrates within the chordate phylum, yet unlike other chordate groups, they evolved a biphasic lifecycle alternating between motile larvae and sessile adults. The papillae of most tunicate larvae are the key sensory-adhesive organ regulating their settlement and metamorphosis. The papillae are nearly always arranged as a group of three morphologically identical organs that arise from an anterior neural plate border region nested between ventral epidermis and more dorsal/posterior neural tube progenitors. Due to their embryonic origin and molecular signatures, this anterior border has been evolutionarily linked to vertebrate placode regions. It was previously shown that the specification, patterning, and morphogenesis of the embryonic papilla region all depend on BMP signaling, though downstream mechanisms remain poorly understood. Here we show that the NKX2-3/5/6 ortholog NK4 is a key transcription factor that acts downstream of BMP signaling to pattern the papillae in the Ciona embryo. We present evidence that NK4 is activated by BMP signaling and encodes a transcriptional repressor that is required to restrict the expression of the papilla regulatory gene Foxg to three cell clusters that give rise to the three papillae. Loss of NK4 function results in the formation of a single large papilla. In contrast, overexpression of NK4 represses Foxg, eliminating the papillae. We also show that the expression of NK4 is restricted dorsally by the BMP antagonist Chordin, while the ventrally-expressed transcription factor Msx can alleviate the repressive effect of NK4, potentially allowing for the characteristic tripartite patterning of the papillae.

Combined lactate- and phosphate-dependent cytoplasmic acidification is associated with Mycobacterium tuberculosis growth arrest at acidic pH

2026-10-09T14:00:00Z

by Adam P. Kibiloski, Shelby J. Dechow, Bassel J. Abdalla, Heather M. Murdoch, Anna D. Tischler, Robert B. Abramovitch

Mycobacterium tuberculosis (Mtb) cultured in minimal medium at acidic pH arrests growth when provided specific single carbon sources, including glycerol, propionate, and lactate, a phenomenon we refer to as acid growth arrest. To define the mechanisms of acid growth arrest on lactate, we selected transposon mutants that grew under these conditions. Five mutants carried insertions in phoT or pstC2, which encode components of a phosphate ABC transporter. Depleting phosphate restored Mtb growth in minimal medium supplemented with lactate at acidic pH, demonstrating that growth arrest on lactate depended on phosphate. The combination of lactate and phosphate at acidic pH acidified the cytoplasm to below pH 6.7, whereas the phoT mutant maintained a cytoplasmic pH > 7.2. Lactate slightly increased membrane potential in wild-type Mtb, whereas the phoT mutant maintained a higher membrane potential. Transcriptional profiling identified a lactate-associated PMF stress signature, including upregulation of electron transport chain genes. Together, these findings associate lactate- and phosphate-dependent cytoplasmic acidification with proton motive force (PMF) stress and acid growth arrest. The phoT mutant grown in lactate at acidic pH upregulated the senX3/regX3 regulon. Using a regX3 mutant, we found that growth on lactate under low-phosphate conditions required regX3. We propose a model in which (1) acidic pH, lactate, and phosphate together modulate cytoplasmic pH homeostasis and are associated with PMF stress and acid growth arrest; and (2) low phosphate induces SenX3-RegX3 activity, which may alter cell-envelope physiology through ESX-5- and PE/PPE-dependent pathways and promote growth on lactate at acidic pH.

New insights into Müllerian duct differentiation provided by single cell transcriptomics in the chicken embryo

2026-10-09T14:00:00Z

by Juan Lan Tan, Adele Barugahare, Andrew Thomas Major, Craig Allen Smith

In vertebrate embryos, Müllerian ducts give rise to the female reproductive tract. Here, we present a comprehensive analysis of Müllerian duct differentiation using single cell transcriptomics in the chicken embryo, a unique model for duct development. The data reveal greater cellular complexity of Müllerian duct differentiation than previously understood. Transcriptomic profiling of early formed Müllerian ducts identifies molecular signatures for the Müllerian duct Epithelium (MDE) and the Müllerian Duct Mesenchyme (MDM), the two principle compartments of the Müllerian duct. The MDE expresses PAX2, LHX1, WNT7, LGR5, PDGFA/D, and CDH1/2. The MDM is marked by WNT4, EMX2, POSTN, OSR1, VIM,DMRT and the EMT markers ZEB1/2. In the male, the regressing mesenchyme (MDM) has a unique molecular signature, expressing the transcription factors MSX1, MSX2, RUNX2, GATA5, DLX3 and DLX5, and the signaling regulators DKK4 and NRG1 (Neuregulin). Single cell transcript profiling of the regressing male mesenchyme identifies new genes implicated in duct regression, including the WNT antagonist, DKK4. DKK4, responds to Anti-Mullerian Hormone induction and can induce duct regression when ectopically expressed in females. The duct mesenchyme in the female follows a different fate, with a molecular signature comprising SMARCA2/ HMGA2/ZEB1/2/TWIST1/2/DMRT2 and persistent expression of FOXE1, OSR2 and HGF (Hepatocyte Growth Factor). Cell clusters in the developing female ducts reflects spatial pre-patterning of the duct prior to later regionalisation. In contrast to AMH-mediated bilateral Müllerian duct regression in males, female chicken embryos show an unusual pattern of left duct differentiation and contralateral right duct regression. We find that right female duct does not regress in the same manner as in males, being transcriptionally distinct and lacking a population of regressing mesenchyme, despite presumably being mediated by AMH, as in males.

Chromatin stability safeguards mitochondrial homeostasis and restrains TORC1 signaling

2026-10-08T14:00:00Z

by Vinoth Sigamani, Mohd Yousuf, Daniel L. Johnson, Brian D. Strahl, R. Nicholas Laribee

Chromatin is dynamically regulated in response to nutrient flux to promote the transcriptional changes needed for adaptation. The mechanistic target of rapamycin complex 1 (yeast TORC1) kinase integrates nutrient signaling with chromatin regulation, yet whether chromatin signals back to regulate TORC1 remains unclear. We find that a histone H3 lysine 37 to alanine (H3K37A) mutant predicted to disrupt a histone-DNA contact promotes histone degradation, hyperactivates TORC1, and causes cytotoxicity upon TORC1 inhibition. This cytotoxicity is specific to H3K37A, since chromatin instability in wild-type histone H3 (H3WT) cells reduces histone abundance and hyperactivates TORC1 without cytotoxicity upon TORC1 inhibition. Combining H3K37A with these chromatin stability mutants exacerbates histone loss, TORC1 hyperactivity, and lethality during TORC1 inhibition. Transcriptome analysis indicates H3K37A deregulates mitochondrial retrograde signaling, which is exacerbated upon TORC1 inhibition and becomes cytotoxic due in part to defective mitochondrial import of an OXPHOS subunit. Retrograde inactivation, or neutralization of reactive oxygen species (ROS) prevents this toxicity. These findings identify chromatin stability as an upstream restraint on TORC1 signaling, revealing bidirectional communication between chromatin and a major nutrient-responsive pathway. They further show H3K37 has an additional functionality that prevents mitochondrial dysregulation during metabolic stress adaptation.

ZBED6 deficiency drives pathological cardiac hypertrophy through MEOX1–ERK1/2–dependent autophagy dysfunction

2026-10-08T14:00:00Z

by Xiao Zhang, Xiaopeng Liu, Ruirui Pan, Huan Liu, Junying Xiao, Xiangkai Leng, Hongmei Zhang, Dengke Pan, Shengzhong Duan, Jiangwei Wu

Pathological cardiac hypertrophy, a major risk factor for heart failure, is regulated by complex transcriptional networks. We previously identified the transcription factor ZBED6 as a key regulator for skeletal muscle hypertrophy, its role in the cardiac hypertrophy remains unexplored. Here, we report that ZBED6 is a key suppressor of pathological cardiac hypertrophy. ZBED6 is markedly reduced in myocardial tissues from patients with cardiac hypertrophy. ZBED6-deficient pigs exhibited cardiac hypertrophy with diastolic dysfunction. Integrative transcriptomic and ChIP-seq analyses identified MEOX1 as a direct negative target of ZBED6. Loss of ZBED6 upregulates MEOX1 transcription, which subsequently activated ERK1/2 signaling, leading to impaired autophagy-induced hypertrophy. Knockdown of MEOX1 reduced ERK1/2 phosphorylation and mitigated cardiomyocyte hypertrophy induced by ZBED6 deficiency. Similarly, pharmacological inhibition of ERK1/2 restored autophagy and alleviated hypertrophy in ZBED6-depleted cardiomyocytes. Collectively, these findings define a previously unrecognized ZBED6–MEOX1–ERK1/2 axis that critically regulates cardiac hypertrophy and represents a potential therapeutic target.

PLOS Genetics: New Articles

Correction: Doxifluridine promotes host longevity through bacterial metabolism

Whole-proteome structure/function prediction in uropathogenic E. coli reveals previously missed host-microbe and microbe-phage interaction pathways

Adjusting for medication status in genome-wide association studies

Enhancing cell type deconvolution in spatial transcriptomics through incorporating multiple reference panels

Genetic architecture of the murine serum metabolome reveals carboxyl esterases as master regulators of circulating fatty acid metabolism

A common pathogenic founder variant in Rwandan breast cancer cases

Conditional-prevalence correction for liability-scale analyses of covariate-adjusted binary GWAS

kri-1/KRIT1 promotes innate immune and lipid homeostasis in the C. elegans intestine

Nicotinic receptor in dopamine neurons mediates learned odor choice

The lipid raft marker flotillin FloA drives relocalization of the plasma membrane H+-ATPase PmaA as a protective response to calcium stress

Recombination rate and efficiency of linked selection in small and large stickleback populations

Fast probabilistic whitening transformation for ultra-high dimensional genetic data

CDH1 loss remodels gene expression and lineage identity in human mammary epithelial cells

The peculiar properties of pericentromeric regions of genomes and their influence on sex chromosome evolution

Auxilin in enteroendocrine cells controls intestinal homeostasis through inter-cell signaling relays

Extensive mobilome heterogeneity in a widespread endosymbiont: A candidate dimeric plasmid and highly fragmented prophages in Wolbachia from Culex pipiens

Distinct core minor pilin complexes prime specialized type IV filaments in cyanobacteria

Multi-omics analysis of high-grade serous ovarian cancers reveals heterogeneity and distinct immunological patterns based upon clinico-genomic status

Meta-analysis of over 8,000 individuals from Hawai‘i and Samoa for genetic associations to cardiometabolic phenotypes

The role of gene regulatory evolution in weapon diversification: Insights from comparative genomics, chromatin profiling, and functional analyses of BMP signaling in horned beetles

NLGN3 autism variants have distinct functional impact on synapses and sleep behavior in Drosophila

Revisiting the impact of synthetic ORF sequences on engineered LINE-1 retrotransposition

Genome-Wide DNA methylation profiling of tissue-plasma pairs identifies Novel cfDNA biomarkers for the diagnosis of gastric cancer

Diversification and functional expansion of archaeal T4F machineries

The AF-2 domain of estrogen-related receptor interacts with PPRC1 to modulate larval epidermal marking in Bombyx mori

An NKX2-3/5/6 homolog is required downstream of BMP signaling to pattern the sensory-adhesive organ of a tunicate larva

Combined lactate- and phosphate-dependent cytoplasmic acidification is associated with Mycobacterium tuberculosis growth arrest at acidic pH

New insights into Müllerian duct differentiation provided by single cell transcriptomics in the chicken embryo

Chromatin stability safeguards mitochondrial homeostasis and restrains TORC1 signaling

ZBED6 deficiency drives pathological cardiac hypertrophy through MEOX1–ERK1/2–dependent autophagy dysfunction

The lipid raft marker flotillin FloA drives relocalization of the plasma membrane H⁺-ATPase PmaA as a protective response to calcium stress