- BioRxiv Biochemistry
- BioRxiv Bioinformatics
- BioRxiv Biophysics
- BioRxiv Cancer Biology
- BioRxiv Pharmacology and Toxicology
- BioRxiv Systems Biology
- BioRxiv Zoology
- by Hopenfeld, B.A multiple channel QRS detector is described. The detector partitions raw signal segments into peak domains, extracts parameters associated with the peak domains, and scores peaks based on these parameters. A multi-layer perceptron (MLP) with 11 inputs generates provisional peak scores, which are refined through application of rules involving 20-30 parameters. An optimal sequence of supra threshold peaks is determined. Separately, combinatorial optimization determines an optimal structured heart rhythm sequence. Adjudication between the general supra threshold sequence and the structured […]
- by Wang, Y., Reshetnikova, E., Katuwal, N. B., Bharti, V., Pereira, M. S., Oppong, B. A., Lee, D. A., Mittra, A., Freud, A. G., Vilgelm, A. E.CDK4/6 inhibitors are standard-of-care for metastatic estrogen receptor-positive (ER+) breast cancer, yet the development of resistance remains a significant clinical hurdle. While CDK4/6 inhibitors are primarily recognized for their ability to induce cytostasis, their role in modulating innate immune responses remains poorly defined. Here, we demonstrated that CDK4/6i treatment remodels the tumor cell surface to favor recognition and elimination by Natural Killer (NK) cells. Using a diverse biobank of patient-derived organoids (PDOs), we found that CDK4/6 inhibition robustly upregulated the […]
- by Li, H., CHIANG, W.-T., Gazestani, V. H., Bao, B., Li, S., Menard, P., Arnsdorf, J., Dalgaard, Z. S., Bjorn, S. P., Brondum, K. K., Hansen, A. H., Schoffelen, S., Voldborg, B. G., Lewis, N. E.Glycosylation is critical to biopharmaceutical activity, stability, and pharmacokinetics. While production cells can be engineered to produce better protein glycoforms, glycans decorate thousands of host cell proteins, and it remains unclear how glycoengineering impacts the host cell. To decipher the cell response to glycoengineering, we studied a library of 166 glycoengineered CHO-K1 cell clones representing 54 different glycosyltransferase modifications. Through integrated analysis of glycomics, RNA-Seq, and phenotypic data, we discovered that glycoengineered mutants clustered into three distinct groups (wild-type-like, Moderate, […]
- by Piano Mortari, E., Laffranchi, M., Cinicola, B. L., Sugoni, C., Barresi, S., Marcellini, V., Agolini, E., Albano, C., Volpe, G., Scarsella, M., Giorda, E., Sparaci, A., Di Prinzio, R. R., Zaffina, S., Quintarelli, C., Milito, C., Anile, M., Quinti, I., Novelli, A., Chen, L., Locatelli, F., Sozzani, S., Carsetti, R.Systemic vaccination induces serum antibodies and circulating memory B cells but provides limited protection in the upper respiratory tract, where many respiratory pathogens initiate infection. How systemic memory B cells contribute to mucosal immunity remains unclear. Using multiparametric flow cytometry, single-cell RNA and V(D)J sequencing, and functional analyses of paired blood and nasal-oropharyngeal samples, we characterized human B cells across systemic and mucosal compartments. Swab-derived B cells transcriptionally overlap with circulating activated memory B cells while exhibiting distinct features of […]
- by Dehghan Manshadi, M., Panchal, N. K., Sun, L.-Z., Setoodeh, P., Zare, H.Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide. Current treatments offer limited efficacy and no definitive cure, underscoring the urgent need for more selective and effective therapeutic strategies. This study investigated the synthetic lethality caused by co-targeting two metabolic genes, ATP citrate lyase (ACLY) and oxoglutarate dehydrogenase (OGDH), in HCC cells. Using valproic acid (VPA) and bempedoic acid (BA) as pharmacological inhibitors of OGDH and ACLY, respectively, we observed a strong synergistic effect in inhibiting the proliferation […]
- by Wang, D., Jin, J., Qiao, J., Wei, L., Wu, S., Liu, Q.Experimental and predicted RNA three-dimensional structures are expanding rapidly, but RNA structure search still lacks a compact residue-level representation that supports database-scale comparison. Using family-held-out ablations across the currently available experimental RNA structure collection, we found that spatial-neighbour features are markedly more informative for family-level discrimination than conventional backbone and base descriptors. Building on this result, we developed RiboSeek, a search framework based on a 20-letter geometric alphabet (RS-20), an 80-letter structure-and-base composite alphabet (RS-80). Across family-level classification and retrieval […]
- by MONFORT, T.Time domain Dynamic full-field optical coherence tomography (D-FFOCT) is a powerful label-free imaging modality that enables functional visualization of cellular activity in living tissues with subcellular resolution. However, its sensitivity remains a major limitation for imaging highly scattering three-dimensional (3D) biological models such as retinal organoids, where incoherent background and inefficient optical flux distribution reduce dynamic contrast and limit imaging depth. In this work, we introduce a ratio-free optical configuration for time-domain D-FFOCT that enables continuous tuning of the sample-to-reference […]
- by Stacpoole, Q., Allan, R. S., Coughlan, H. D., Iannarella, N., Johanson, T. M.During ageing, hematopoietic stem cells (HSCs) have reduced regenerative potential, skewed differentiation toward the myeloid lineage, and heightened susceptibility to clonal expansion and malignancy. While epigenetic alterations are well documented, the impact of aging on higher-order 3D chromatin architecture remains poorly understood. Here, we examined the 3D genome organisation of aged murine HSCs using in-situ Hi-C then integrated this with gene expression and chromatin accessibility data to build HiC-informed gene regulatory networks (GRNs). Aged HSCs display erosion of topologically associating […]
- by Xu, A. Q., Hung, M. S., Chen, B., Sopena, M. L., Chakravarty, P., Camara, A., Calado, D. P.Booster vaccination can restore antibody titres and protection, but whether it improves long-term durability by expanding plasma cell (PC) numbers or also by shifting PC fate toward intrinsically longer-lived states remains unclear. Here we established longitudinal in vivo ground truth for PC persistence by combining PC-specific genetic timestamping, clonal tracking, and multi-timepoint single-cell profiling across spleen and bone marrow. We resolved PC longevity as a layered, non-binary architecture comprising short-, intermediate-, and long-lived programs, and showed that program identity is […]
- by Chakraborty, R., Shah, R., Akter, M., Shahbazi, M.-A., Tukova, A., Shannon, K.Cancer cell membrane coated biomimetic nanoparticles have been shown to be highly efficient in cellular uptake, homotypic tumour targeting, and the ability to suppress tumour growth compared to uncoated nanoparticles. Long duration anti-cancer treatment regimens require highly stable cancer cell membrane coated biomimetic nanoparticle. To manufacture such highly stable cancer cell membrane coated biomimetic nanoparticle, we used Click-chemistry to encapsulate cancer cell membrane on nanoparticles. In situ characterization was done to confirm the functionality of the novel Click-chemistry based formulation […]
- by Suhre, K.In 2003, Suhre and Claverie demonstrated that the difference between the fraction of charged amino acids and the fraction of polar uncharged amino acids in a proteome (the CvP-bias) was the single genomic feature that most strongly discriminates hyperthermophilic microorganisms from their mesophilic and thermophilic counterparts. The original analysis was based on 71 completely sequenced genomes available at the time. Here, using modern genome databases – specifically the Bacterial and Viral Bioinformatics Resource Center (BV-BRC) for curated optimal growth temperature […]
- by King, C., Iqbal, M., Shokati, E., Man Ying Li, C., Li, R., Tomita, Y., Smith, E., Kawecka, J. A., Wang, S., Fenix, K.Immune receptor profiling enables tracking of individual T or B cell clones across time and tissues, providing insight into immune responses, cancer, and autoimmunity. When combined with single-cell transcriptomics, it links clonotype identity to cellular function, revealing the diversity and dynamics of immune cell populations. This study presents a head-to-head benchmarking comparison of two single-cell immune profiling technologies: droplet-based microfluidics from 10x Genomics (10x) and combinatorial barcoding from Parse Biosciences (Parse). Using matched human samples from PBMC's, the analysis evaluates […]
- by Strashnov, P., Shevtsov, A., Meshchaninov, V., Kardymon, O., Vetrov, D.Motif scaffolding in protein design involves generating complete protein structures while preserving the 3D geometry of designated structural fragments, analogous to image outpainting in computer vision. Current benchmarks focus on functional motifs, leaving general geometric preservation capabilities largely untested. We introduce GeomMotif, a systematic benchmark that evaluates arbitrary structural fragment preservation without requiring functional specificity. We construct 57 benchmark tasks, each containing one or two motifs with up to 7 continuous fragments, by sampling from the Protein Data Bank (PDB) […]
- by Nakanishi, K., Shimizu, H.Rheumatoid arthritis affects millions of people worldwide, yet a substantial fraction of patients fail to achieve lasting benefit from current therapies. AI-based virtual cell models offer a promising route to simulate the effects of thousands of potential drug targets computationally, but whether their predictions genuinely reflect what happens in the disease-relevant cells of patients undergoing treatment has been unclear. Here, we introduce ImmunoSTATE, a clinically anchored framework that benchmarks empirical and virtual perturbations directly against patient-derived treatment trajectories in pathogenic […]
- by Yang, Y., Zhao, L., Orouji, S., Zhu, Y., Johnson, R. L., Maxwell, D. S., Mica, I., Russell, K. P., Al-lazikani, B.Confirming target engagement in tumor experimental models remains a major challenge in oncology drug development. Pharmacodynamic biomarkers can help address this, but few systematic resources link drug targets to candidate biomarkers. We developed TargetTrace, a comprehensive resource to identify and prioritize pharmacodynamic biomarkers across nine key target classes, including transcription factors/cofactors, kinases, phosphatases, ubiquitin ligases, deubiquitinases, acetyltransferases, deacetylases, methyltransferases, and demethylases. Biomarker candidates were gathered from curated molecular interaction resources and refined using external annotations to improve accuracy. For enzyme […]
- by Pallais, J. P., Razzoli, M., Rodriguez, P., McGonigle, S., Daugherty, A., Hillman, H., Verteramo, L., Schrank, P., Parthiban, P., Chang, X., Wang, H., Veglia, G., Koehl, J., Bose, M., Ehrlich, M. E., Salton, S., Araque, A., Lettieri Barbato, D., Revelo, X., Ruan, H.-B., Williams, J. W., Bartolomucci, A.Microglia, the resident macrophages of the central nervous system, are recognized for their heterogeneity and integral role in brain function and diseases. In the context of high fat diet (HFD) feeding and obesity, microglia become overactive, acquiring a prevailing lipid associated microglial phenotype (also known as LAM). Yet, how microgliosis is induced and regulated remains unclear. Here we report a key role for the Complement 3a Receptor (C3aR), on HFD-induced hypothalamic gliosis and weight gain in mice. HFD consumption leads […]
- by Silva de Almeida, B. L., Bonidia, R., Bole, M., Avila-Santos, A., Stadler, P. F., Nunes da Rocha, U., de Carvalho, A. C. P. L. F.The prediction of biological sequence properties has traditionally relied on alignment-based methods that assume evolutionary homology and depend on curated reference databases. This, in turn, limits scalability and sensitivity for large or heterogeneous datasets, remote homologs, short sequences, and rapidly evolving genomic regions. Although Machine-Learning (ML) approaches offer alignment-free alternatives, their broader adoption is limited by: (i) the lack of standardized, externally validated benchmark models across diverse datasets, and (ii) the technical expertise required for feature engineering, model selection, and […]
- by Soler-Saez, I., Galiana-Rosello, C., Grillo-Risco, R., Falony, G., Tepav?evi?, V., Vieira Silva, S., Garcia-Garcia, F.Biological sex is a key determinant in the onset and progression of multiple diseases. In multiple sclerosis (MS), females exhibit higher disease prevalence, earlier onset, and more pronounced inflammatory activity, whereas males tend to experience a more severe neurodegenerative course, characterized by accelerated central nervous system damage and increased brain atrophy. The gut microbiome has emerged as a critical factor in MS, as its composition can either ameliorate or exacerbate disease progression. In this study, we aimed to identify reproducible […]
- by Rinon, E. M., Visaya, M. V., Sambayan, R.Kernel methods offer a robust framework for integrating multi-modal datasets into a unified representation, thereby facilitating more comprehensive data interpretation. In the presence of incomplete datasets, multiple kernel learning is employed to enhance the efficiency of data completion and integration. We investigate kernel-based approaches to address the incomplete-data problem with applications to yeast protein data. Biological data such as yeast proteins can be represented through multiple modalities, including gene expression profiles, amino acid sequences, three-dimensional structures, and protein interaction networks. […]
- by Gordon, E. M., Rajesh, A., Chauvin, R. J., Labonte, A., Adeyemo, B., Dworetsky, A., Lynch, C. J., Krimmel, S. R., Cho, P., Wang, A., Baden, N. J., Scheidter, K. M., Monk, J., Metoki, A., Ren, J., Nishino, T., Park, Y., Rafka, E., Pruett, J. R., Kepecs, A., Liu, H., Fair, D. A., Liston, C., Woo, C.-W., Kay, B. P., Marek, S., Petersen, S. E., Sylvester, C. M., Schwarzlose, R. F., Raichle, M. E., Laumann, T. O., Dosenbach, N. U. F.Task fMRI and electrophysiology have revealed distributed, linked cortical patches with shared category preferences (e.g., faces, objects, places) smaller than cytoarchitectonic areas. Resting-state functional connectivity (RSFC) similarly showed that somato-cognitive action network (SCAN) nodes interleave with effectors (foot, hand, mouth), subdividing the precentral gyrus. Here, using multiple precision functional mapping (PFM) modalities (RSFC, task, lags), we discovered that most of association cortex is organized like face processing and SCAN, with small, discrete patches interconnected into chains. Such patch-chains densely tile […]