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Chemical genomics screening reveals novel functions for unannotated genes in Vibrio cholerae C6706

Vibrio cholerae, the causative agent of cholera, remains a major global health burden despite ongoing initiatives for vaccination and improved sanitation. Much of the V. cholerae lifecycle occurs in aquatic environments, requiring gene functions that enable survival under multiple stresses associated with this niche and during the transition to the human host. Although numerous V. cholerae genome sequences are available, functional annotation across its pan-genome remains incomplete, limiting...

— Haycocks, J. R., Ahmad, H., Alao, M., Williams, G., Sutherland, S., Graham, C. L., Sharma, P., Moynihan, P., Glinkowska, M., Grainger, D. C., Moradigaravand, D., Banzhaf, M. 2026-01-17 00:00:00

Scaling perturbations: beyond genome-scale CRISPR screens

CRISPR screens have become essential tools for systematically probing gene function from basic biology to drug discovery, yet important frontiers remain beyond genome scale. Probing regulatory elements, interpreting genetic variants, and mapping genetic interactions all challenge the sensitivity and scalability of existing approaches. Here we introduce two synergistic technologies to address these limitations. PORTAL (Perturbation Output via Reporter Transcriptional Activity in Lineages) shif...

— Tang, A., Ardy, R. C., Mendes, R. E., Norman, T. M. 2026-01-17 00:00:00

Quality control of blood plasma for mass-spectrometry proteomic research

Mishandling of samples during blood plasma preparation may lead to biases in proteomic analysis and false interpretation of data. Previous plasma proteome profiling study (Geyer, Mann et al., 2019) described proteins that may serve to indicate poor plasma sample quality. We have established a targeted quantitative method for three prominent panels of markers proposed by previous study for exclusion of hemolyzed and coagulation samples. We conducted a model experiment similar to Geyer, Mann et...

— Vakaryuk, A. V., Butenko, I. O., Kitsilovskaya, N. A., Kovalenko, A. V., Gremyacheva, V. D., Kozhemyakin, G. L., Lebedeva, A. A., Baraboshkin, N. M., Fedorov, O. V., Govorun, V. M. 2026-01-16 00:00:00

Addressing diagnostic gaps in thyroid pathology: a multiplex protein panel as an adjunctive tool for risk stratification and differentiation of thyroid neoplasms

This study aims to identify a panel of human plasma protein biomarkers to improve the diagnosis and risk stratification of thyroid neoplasms. The diagnosis of thyroid neoplasms is challenging due to limitations of existing methods, necessitating auxiliary tools for differentiating between benign and malignant cases. In this research, 386 plasma samples from patients with various types of thyroid neoplasms were analyzed using HPLC-MS. Nineteen proteins with differential expression were identif...

— Kitsilovskaya, N. A., Butenko, I. O., Vakaryuk, A. V., Kovalenko, A. V., Gremyacheva, V. D., Kozhemyakin, G. L., Lazareva, A. A., Lebedeva, A. A., Baraboshkin, N. M., Fedorov, O. V., BONDARENKO, E. E., IOUTSI, V. A., AKSENOVA, T. N., MOKRYSHEVA, N. G., Govorun, V. M. 2026-01-16 00:00:00

Serial enrichment based quantitative proteomics enables deep and multiplexed profiling of post-translational modifications

Post-translational modifications (PTMs) play central roles in regulating protein function, localization, stability, and signaling networks. Comprehensive characterization of multiple PTMs, however, remains technically challenging due to limited sample availability, enrichment incompatibilities, and analytical complexity. Here, we present an integrated serial enrichment workflow that enables quantitative profiling of multiple PTMs from a single biological sample. Using a streamlined strategy c...

— Najar, M. A., Aravind, A., Prasad, T. S. K., Modi, P. K. 2026-01-16 00:00:00

A protein language model unveils the E. coli pangenome functional landscape regulating host proteostasis

Understanding how bacterial diversity at strain level resolution shapes host physiology is a central challenge in microbiome research. The vast, functionally unknown genetic diversity within a species pangenome makes it difficult to connect genes to function and their impact on host physiology. Here, we explore how the functional landscape of the Escherichia coli pangenome impacts transcriptional responses in Caenorhabditis elegans and show that traditional gene-centric methods fail to provid...

— Martinez, D. M., Aprodu, A., Backes, C., Ottens, F., Zecic, A., Doherty;, H., Widder, J., Andrew, I., Game, L., Kaneva, I., Roumellioti, G., Montoya, A., Kramer, H., Hoppe, T., Cabreiro, F. 2026-01-15 00:00:00

Synthetic Data to Explore Transcriptional Regulation of Differentially Expressed Genes in Ovarian Cancer

In major diseases like cancer, many genes are dysregulated. While differential expression (DE) analyses help identify these genes, they do not reveal the transcriptional regulatory landscape between control and disease states. Here, we developed a process-driven model based on generalized stochastic transcriptional regulation (TR) to study DE genes in ovarian cancer. We generated over 39,000 synthetic gene expression profiles based on RNA-seq dataset of 11 samples (5 control FTE and 6 ovarian...

— Zhang, S., Selvarajoo, K. 2026-01-15 00:00:00

Proteomic Profiling of Human Omental and Subcutaneous Adipose Tissue in Individuals with a Broad Range of BMI.

Obesity is a major public health challenge affecting an ever-increasing proportion of the global population. It is associated with numerous comorbidities. Progressive expansion and remodeling of adipose tissue may lead to depot specific changes in adipose tissue biology and energy partitioning. Such changes likely precede the development of obesity-related complications. To facilitate a deeper understanding of adipose tissue biology, a comprehensive and quantitative proteomic dataset at the p...

— Zelter, A., Wen, Y. W., Riffle, M., Czuba, L., Yadav, A. S., Zhu, J., Snyder, J. M., Maurais, A., LaFrance, J. M., Khandelwal, S., Chen, J. Y., Williams, E. J., Parr, Z., Kim, D., Rubinow, K. B., MacCoss, M. J., Isoherranen, N. 2026-01-15 00:00:00

Salmonella sensitizes macrophages for context-dependent anti-inflammatory response

Macrophages critical role in the innate immune response depends on their ability to change their activation state in response to environmental signals, generating cells with diverse functions ranging from antimicrobial activity to tissue repair. However, this plasticity in activation state represents a vulnerability that intracellular pathogens have evolved to exploit. Salmonella Typhimurium (STm) harnesses macrophage plasticity to promote anti-inflammatory states conducive to bacterial survi...

— Alvarado, G., Lane, K. 2026-01-14 00:00:00

Microbiome-Derived Metabolites Shape CD4⁺ T-Cell Differentiations and Immune Aging in Chronic HIV-1 Infection

The role of aromatic gut-derived bacterial metabolites (GDBMs) in shaping immune cell metabolism and function remains poorly explored. Using ex vivo metabolomic profiling of paired plasma and CD4 T-cells from people living with HIV-1 (PLWH), we identified a network of aromatic GDBMs whose cell-associated abundance, rather than systemic levels, was linked to broad alterations in CD4 T-cell metabolic and functional states. Among these metabolites, p-cresol sulfate (PCS) emerged as a mechanistic...

— Da Silva, A. C., Flantzer, L., Weinberg, J., Kyu, S., Daley-Bauer, L. P., Santana, A. C., Talla, A., Rittgers, A. L., Welbourn, S., Gordon, D. E., Tomalka, J., Marconi, V. C., Jones, D. P., Younes, S.-A. 2026-01-14 00:00:00

Metabolomic changes underpinning permethrin resistance in the Anopheles gambiae malaria vector from Cameroon

Insecticide resistance reduces the effectiveness of current malaria vector control interventions. To understand the mechanisms underlying permethrin resistance in field-derived Anopheles gambiae vectors collected from Cameroon, we used Ultra-High Performance Liquid Chromatography coupled with High-Resolution Tandem Mass Spectrometry (UHPLC-HRMS/MS) to comprehensively analyze metabolic changes in resistant and susceptible samples to gain insight into mechanisms driven permethrin resistance. Re...

— DJOVA, S. V., Christopher, M. W., Ibrahim, S. S., Kouamo, M. F. M., Dinglasan, R. R., Garrett, T., Wondji, C. S. 2026-01-14 00:00:00

If the shoe fits? -- technical nuances of plasma proteomic workflows in clinical and preclinical contexts

The push for new clinical biomarkers has seen rapid innovation in biofluid analysis, particularly for plasma. For mass-spectrometry (MS)-based analysis, achieving depth and quantitative accuracy whilst ensuring throughput continues to shape plasma methods development. Numerous workflows have emerged that mitigate high-abundance suppression and expand dynamic range, especially when paired with next-generation MS instrumentation. Yet systematic evaluations that also consider biological variable...

— Emery-Corbin, S. J., Steele, J. R., Multari, D. H., Tanuwidjaya, E., Hanchapola, I., Sivaraman, K. K., Lee, H.-C., Blundell, S. A., Ali, I., O'Brien, T. J., Faridi, P., Schittenhelm, R. B. 2026-01-13 00:00:00

Bayesian BiLO: Bilevel Local Operator Learning for Efficient Uncertainty Quantification of Bayesian PDE Inverse Problems with Low-Rank Adaptation

Uncertainty quantification in PDE inverse problems is essential in many applications. Scientific machine learning and AI enable data-driven learning of model components while preserving physical structure, and provide the scalability and adaptability needed for emerging imaging technologies and clinical insights. We develop a Bilevel Local Operator Learning framework for Bayesian inference in PDEs (B-BiLO). At the upper level, we sample parameters from the posterior via Hamiltonian Monte Carl...

— Zhang, R. Z., Miles, C. E., Xie, X., Lowengrub, J. 2026-01-12 00:00:00

BiLO: Bilevel Local Operator Learning for PDE Inverse Problems

We propose a new neural network based method for solving inverse problems for partial differential equations (PDEs) by formulating the PDE inverse problem as a bilevel optimization problem. At the upper level, we minimize the data loss with respect to the PDE parameters. At the lower level, we train a neural network to locally approximate the PDE solution operator in the neighborhood of a given set of PDE parameters, which enables an accurate approximation of the descent direction for the upp...

— Zhang, R. Z., Miles, C. E., Xie, X., Lowengrub, J. S. 2026-01-12 00:00:00

Modulation of Cysteine modifications upon short time T-cell activation

T cell activation is initiated by rapid and tightly regulated signaling events that rely on reversible post-translational modifications to ensure speed, specificity, and fidelity. While phosphorylation is well established as a central regulator of T cell receptor signaling, the contribution of cysteine-based modifications remains poorly defined at a systems level. Due to their redox-sensitive thiol side chains, cysteine residues can undergo rapid and reversible chemical modifications, enablin...

— Larsen, M. R., Mandal, K., Jensen, P. T. 2026-01-12 00:00:00

Speed-Dependent Turning Strategies in Quadrupedal Locomotion: Insights from Computational Modeling

Quadrupedal animals like mice navigate their environments through complex coordination of neural signals and biomechanical movements, enabling stable and directed locomotion. While many computational models simplify this process by assuming left-right symmetrical body movements and focusing on straight-line paths, real animals rely heavily on asymmetrical body movements to execute turns and adjust speed effectively. This study builds upon a previously developed model of quadrupedal locomotion...

— Molkov, Y. I., Mohammed, M. A. Y., Stell, T., Harralson, A., Jeter, R., Rybak, I. A. 2026-01-12 00:00:00

Metabolic blueprints of monocultures enable prediction and design of synthetic microbial consortia

Synthetic microbial ecology aims at designing communities with desired properties based on mathematical models of individual organisms. It is unclear whether simplified models harbor enough detail to predict the composition of synthetic communities in metabolically complex environments. Here, we use longitudinal exometabolite data of monocultures for 15 rhizosphere bacteria to parametrize a consumer-resource model, which we use to predict pairwise co-cultures and higher order communities. The...

— Bald, S., Zhang, J., Nelson, R., Scott, D. C., Dukovski, I., de Raad, M., Northen, T., Segre, D. 2026-01-12 00:00:00

Proteo-transcriptomics and morphometrics of teleost cardiac cells define regulatory networks and exercise-induced cardiomyocyte hypertrophy and hyperplasia

Zebrafish and medaka are powerful cardiovascular models, yet cellular and molecular investigations of adult heart cells have been constrained by suboptimal dissociation and characterization methods. To overcome these barriers, we developed a physiological-temperature workflow that generates high-yield, viable single-cell suspensions for FACS, imaging, and low-input molecular profiling. Using transgenic fluorescent reporters, we consistently isolate [~]6,000 cardiomyocytes per adult zebrafish ...

— Contreras, O., Smith, G., Santiago, C. F., Dey, M., Thekkedam, C., Chand, R., Gonzalez-Rajal, A., Zhong, L., Wong, E., Fatkin, D., Harvey, R. P. 2026-01-12 00:00:00

Intrinsic sodium regulation by Na,K-ATPase: The blue crab's salinity adaptation described by a single negative feedback loop

AbstractThe term enantiostasis was introduced by Mangum and Towle to describe functional relationships between environmental changes and an organisms adaptation to them, and furthermore, to distinguish this kind of adaptation from homeostatic control. The defining example of enantiostasis is the blue crabs blood salinity response when exposed to different environmental salinities during the organisms move between the ocean and upriver fresh-water conditions. In this paper an internal negative...

— Ruoff, P. 2026-01-09 00:00:00

Environmental Toxin Rotenone Drives LRRK2-Mediated Microtubule, Cilia and Proteostasis Disruption in Parkinson's Disease Model

Exposure to the environmental toxin rotenone increases risk for Parkinsons disease (PD). However, protein phosphorylation changes induced by rotenone in neural-derived cells have not been reported. We examined the effect of rotenone on the proteome and phosphoproteome of cortex-derived cultures from wild-type and Lrrk2-/- mouse brains. We also analyzed the phosphoproteome of the PD cadaver brain using a previously unanalyzed dataset. Rotenone alters phosphorylation at 904 sites, most of which...

— Flinkman, D., Deshpande, P., James, P., Coffey, E. 2026-01-09 00:00:00

The Red Rice Bran Extract (RRBE) Mitigates Photoaging by Targeting Mitochondrial Oxidative Stress and Regulating Thermal Damage Responses

The photoprotective efficacy of natural skin-active complexes is well recognized, yet their application is often hindered by the challenge of deciphering their complex, multi-component, and multi-target mechanisms. To bridge the gap between established phenotypes and molecular mechanisms, we developed an AI-driven integrated platform that combines phytochemical profiling, network pharmacology, and deep learning-based target prediction with rigorous biophysical validation. We applied this plat...

— Lin, T.-S., Chen, Y., Li, X., Ji, X., Huang, S., Lyu, J., Li, L., Zuo, H., Li, S., Li, J., Huang, H.-Y., Zhuo, H., Zhang, X., Wang, Y.-F., Ning, S., Zhang, Z., Gu, Y., Zhang, T., Lin, Y.-C.-D., Huang, H.-D. 2026-01-08 00:00:00

Complement Factor H (Y402H) polymorphism for age-related macular degeneration alters retinal lipids

Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is associated with multiple risk factors and involves death of the retinal pigment epithelium (RPE). We investigated how the Y402H polymorphism of Complement Factor H (CFH) and cigarette smoke extract (CSE), major AMD genetic and environmental risks, affect lipid metabolism in RPE differentiated from induced pluripotent stem cells (iPSC-RPE) that were derived from human donors genotyped for low-risk (LR) or...

— Shang, P., Hoang, J., Hong, E., Geng, Z., Ambrosino, H., Abnoosian, E., Zhu, X., Ma, M., Wei-Navarro, N. A., Webber, B. R., Qu, J., Montezuma, S. R., Agbaga, M.-P., Dutton, J. R., Ferrington, D. A. 2026-01-07 00:00:00

MetaNetMap: automatic mapping of metabolomic data onto metabolic networks

MotivationMetabolic networks represent genome-derived information about the biochemical reactions that cells are capable of performing. Mapping omic data onto these networks is important to refine model simulations. However, metabolomic data mapping remains very challenging due to difficulties in identifier reconciliation between annotation profiles and metabolic networks. ResultsMetaNetMap is a Python package designed to automatise the process of mapping metabolomic data onto metabolic netw...

— Muller, C., Audemard, J., Prigent, S., Frioux, C. 2026-01-05 00:00:00

Efflux pump regulation and metabolic rewiring define the ceiling of efflux-mediated drug resistance in Mycobacteria

Multidrug-resistant efflux pumps play a critical role in antimicrobial resistance, yet the physiological limits of their overexpression remain poorly understood. While gene amplifications and regulatory mutations commonly drive this overexpression, these pumps remain transcriptionally inactive under normal cellular conditions due to their high energetic cost, making it challenging to assess their full impact on resistance evolution and the maximum attainable minimum inhibitory concentration (...

— Sharma, S., Mehra, S. 2026-01-05 00:00:00

Distinct mechanisms drive post-antibiotic Tuberculosis relapse post-cure versus post-treatment-failure

Tuberculosis (TB) remains a global health concern, as Mycobacterium tuberculosis (Mtb) infects a quarter of the worlds population. Though many TB patients sterilize infection with treatment regimens including the current standard, incomplete sterilization leads to post-treatment relapse and development of drug resistance. Two mechanisms have been hypothesized as driving relapse: persistence, where treatment kills all replicating Mtb, and relapse follows once non-replicating Mtb return to a re...

— Michael, C. T., Budak, M., Lin, P. L., Kirschner, D. E. 2026-01-05 00:00:00

Mass Spectrometry-Based Profiling of Personalized Immunopeptidomes in Thai Renal Cell Carcinoma

This study profiles the personalized immunopeptidomes of 13 Thai patients with renal cell carcinoma (RCC), addressing a critical knowledge gap in Southeast Asian populations characterized by distinct HLA allele distributions. We combined whole-exome sequencing (WES)-based personalized proteome construction with liquid chromatography-tandem mass spectrometry (LC-MS/MS), using both database-driven searches and de novo peptide sequencing. HLA typing identified seven alleles not previously repres...

— Somparn, P., Sriswasdi, S., Wongkongkathep, P., Muanwien, P., Nanthawong, S., Apinan, T., Opanuraks, J., Shuangshoti, S., Hirankarn, N., Moonmuang, S., Kampoun, T., Chaiyawat, P., Pisitkun, T. 2026-01-03 00:00:00

NAViFluX: a visualization-centric platform for interactive analysis, refinement and design of genome-scale metabolic networks

Genome-scale metabolic network (GSMN) models are rigorously curated, cellular-level representations of metabolism that enable flux-based metabolite fate discovery, metabolic engineering, drug target identification and context-specific multi-omics integration. However, the inherent complexity of model architectures, need for programming skills and limited visualization support restrict their broader applicability. Existing tools focus on visualization and analyses separately, necessitating too...

— Krishnamurthy, M. B., P S, H., Subramanian, A. 2026-01-03 00:00:00

Single-cell growth rate fluctuations contribute independently from protein production to gene expression noise and decrease with average growth rate

Phenotypic heterogeneity is a universal feature in microbial life and has profound consequences for the behavior of single cells. However, dissecting and quantifying the sources of phenotypic noise is challenging as it requires precise quantification of the dynamics of gene expression fluctuations in vivo. Here, we analyze time-lapse microscopy data of single E. coli cells carrying fluorescent reporters for constitutive and ribosomal promoters to quantify how fluctuations in protein productio...

— Kscheschinski, B., Chauvin, D., Julou, T., van Nimwegen, E. 2026-01-02 00:00:00

An Agent-Based Model of Protein Polymerization Dynamics: Focus on the Actin System

Actin polymerization is a critical cellular process involved in a wide range of activities, from cell motility to cytokinesis. The complex behavior of this molecular system, resulting in three different phases (i.e., nucleation, elongation, and steady state) is clear by looking at the way these dynamics emerge from a large number of interactions between different proteins, regulatory elements, and signaling pathways. In this article, we present an agent-based model of actin polymerization dyn...

— Tarantino, R., Contino, S., Gugliotta, L., Indelicato, G., Panunzi, G., Bertolazzi, G., Romano, V. 2026-01-02 00:00:00

Long-range neural pathways for octopus chemotactile processing revealed from periphery-to-brain by centimeter-field microCT

Understanding how nervous systems mediate responses to sensation requires whole-body maps of periphery-to-brain connections. Octopuses exemplify this challenge with distributed control of eight arms and hundreds of suckers, yet their long-range microanatomical wiring remains elusive due to limitations in microscopy. We extend histotomography (Ding et al. 2019), a form of soft tissue microCT customized for volumetric characterization of cells and tissues, to centimeter range with a custom micr...

— Vanselow, D. J., Sugarman, A. L., Northover, D., Senft, S., Zaino, C. R., Yakovlev, M. A., Christ, J. M., Silverman, J., Chung, W.-S., La Riviere, P., Hanlon, R. T., Cheng, K. C., Ang, K. C., Ngu, M. S. 2026-01-02 00:00:00