Biology subjects

Petrov, P.

Publications and source records attributed to Petrov, P..

13 recordsLinked to original sources

bioRxiv2026

cran2crux: automatically create CRUX ports for R-packages

MotivationR together with CRAN and Bioconductor provides one of the richest ecosystems for bioinformatics and computational biology, with thousands of specialized packages. While GNU/Linux is a vastly-used operating system in this field, R-packages are typically managed independently of the systems native package manager. This separation makes installation, updates and mass rebuilds cumbersome. CRUX, a minimalist semi-source GNU/Linux distribution, offers great flexibility with its ports-based system for the seamless integration of R-packages with its native package manager. ResultsThe hereby presented cran2crux tool automatically generates CRUX ports for packages from both CRAN and Bioconductor. It performs recursive dependency resolution, handles naming conventions, extracts dependencies information, and supports inclusion of optional dependencies. The tool also provides convenient functions for checking updates and regenerating outdated ports. It can generate over 140 ports for complex packages such as Seurat in approximately 11 seconds, dramatically simplifying the maintenance of large R-dedicated repositories on CRUX. Availabilitycran2crux is available under the MIT license at https://github.com/izzilab/cran2crux. As of now, more than 650 R package ports, generated with the tool, are available in the CRUX ports database.

bioinformatics↗

bioRxiv2026

MatriSpace: Identification and visualization of spatially resolved ECM gene expression patterns in health and disease

The extracellular matrix (ECM) is a highly dynamic network of proteins forming the structural organizer of all tissues. Different cell populations contribute to the assembly of the 150+ proteins of a functional ECM. In addition, different ECM subtypes, supporting distinct cellular functions, are found in every organ. Spatial transcriptomics (ST) provides a unique, yet untapped, opportunity to identify which cell populations contribute to ECM production with spatial context. Applied to healthy and diseased samples, this method can identify ECM changes that could be exploited for therapeutic purposes. Here, we introduce MatriSpace, a computational framework to mine ST datasets with a focus on ECM genes. MatriSpace offers two operating modes: researchers can either upload their own ST datasets or explore a large collection of public datasets. Upon analysis, MatriSpace returns spatially resolved maps of matrisome gene expression in relation to cell populations, at multiple levels: from single-gene analysis to tissue niches and functional ECM units. MatriSpace is available as an R package and an online Shiny App (https://matrinet.shinyapps.io/matrispace), making it accessible to all users regardless of their level of expertise. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=97 SRC="FIGDIR/small/720198v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@3f8e28org.highwire.dtl.DTLVardef@8e20beorg.highwire.dtl.DTLVardef@107be22org.highwire.dtl.DTLVardef@153b911_HPS_FORMAT_FIGEXP M_FIG C_FIG KEY POINTSO_LIMatriSpace is a computational framework to interrogate ECM gene expression in spatial transcriptomic datasets. C_LIO_LIResearchers can upload their own spatial transcriptomic datasets for processing by MatriSpace. C_LIO_LIResearchers can interrogate a vast collection of public datasets of healthy and diseased tissues through MatriSpace. C_LIO_LIMatriSpace can identify, quantify, and interpret spatial expression patterns of matrisome genes, gene sets, and niches. C_LIO_LIMatriSpace can uncover regional coordinations of matrisome components and their relationships with non-matrisome genes, such as matrisome receptors. C_LI

systems biology↗

bioRxiv2026

NaVis: a virtual microscopy framework for interactive, high-resolution navigation of spatial transcriptomics data

Despite the widespread adoption of spatial transcriptomics (ST), revealing the alignment between transcriptional layers and tissue morphology remains technically demanding, typically requiring proficiency across multiple computational frameworks and thereby limiting accessibility for a substantial fraction of the biomedical community. Here, we introduce NaVis (https://github.com/Izzilab/NaVis), a point-and-click virtual microscopy framework that redefines ST analysis as an interactive, image-centric experience. NaVis enables rapid high-resolution inference from low-resolution whole-transcriptome platforms, producing microscopy-like visualizations while preserving transcriptome-wide coverage. It further decomposes histological images into quantitative tissue architecture priors - nuclei-rich regions, fibrillar extracellular matrix, and soft tissue - allowing direct integration of gene expression with local morphology. This unified representation supports analyses of compartment enrichment, boundary concordance, spatial cross-correlation, morphological patterning, histology-expression decoupling, and transcriptome-wide spatial similarity. By coupling transcriptomic and image-derived information within an interactive framework, NaVis shifts ST from static computational workflows to an exploratory modality, broadening its accessibility, conceptual reach and potential for biological discoveries.

bioinformatics↗

bioRxiv2025

Fusogen-induced recovery of spinal cord function andmorphology after complete transection

BackgroundSpinal cord injury is a critical issue in neurosurgery, lacking established clinical methods for functional restoration. This study reports the effects of a fusogen sealant, composed of polyethylene glycol and chitosan, in an experimental model of complete spinal cord transection in pigs. ObjectiveTo evaluate the functional and morphological recovery of the spinal cord in an animal model of complete transection following treatment with a polyethylene glycol-chitosan conjugate. Materials and methodsHungarian Mangalica pigs (m = 20.0 {+/-} 2.0 kg, N = 5) underwent complete transection of the thoracic spinal cord, followed by an extended laminectomy and transpedicular fixation. In the experimental group (N = 3), a synthesized gel based on a polyethylene glycol-chitosan conjugate was applied to the spinal gap; the other group (N = 2) served as a control. The postoperative period lasted 60 days and included multi-component rehabilitation. Clinical-functional status was assessed using established neurological scales. In vivo retrograde tracing of the spinal cord was performed using hydroxystilbamidine (FluoroGold). Following the experiment, immunofluorescent histology was conducted using primary antibodies to neurofilament (NF-200), a fluorochrome-conjugated secondary antibody, and the nuclear dye 4,6-diamidino-2-phenylindole (DAPI). The resulting morphology was examined via fluorescence and light microscopy. ResultsControl animals maintained lower paraplegia, anesthesia, and pelvic dysfunction throughout the experiment. In contrast, the experimental group showed positive changes, including the return of sensation from day two. By the end of the study, all animals in this group could assume an upright posture and ambulate on all limbs. These outcomes were statistically significant. Microscopy revealed axons traversing the injury site in the experimental group, whereas control samples showed degenerative post-traumatic changes. ConclusionsThis study demonstrates that a fusogen sealant based on a polyethylene glycol-chitosan conjugate promotes significant morphofunctional recovery after complete spinal cord transection, supporting its therapeutic potential.

neuroscience↗

bioRxiv2025

A phrenic-sparing cephalic reanastomosis model: Acute effects and implications

BackgroundHead transplantation (HT), also known as cephalosomatic anastomosis (CSA), is a surgical procedure proposed as a potential method to extend lifespan in cases of terminal bodily failure. CSA requires a thorough evaluation of each step using appropriate experimental animal models, with pigs being particularly suitable due to their anatomical and physiological similarities to humans. The critical challenge in HT is spinal cord fusion, which current research suggests can be facilitated using fusogens. To refine the technical aspects of the procedure, we conducted head replantation in a pig model using polyethylene glycol (PEG)-chitosan conjugate (Neuro-PEG). In this article, we evaluate the technical aspects of this procedure, the rate of recovery of ventilation after spinal cord fusion, and phrenic sparing in a model of autologous decapitation-reanastomosis in a single swine. MethodsA Hungarian Mangalica pig was submitted to surgical separation of the head while maintaining blood flow to the brain through cannulation of the primary cervical vessels. After cephalic separation, the head was reconnected, and the cervical spinal cord fused. ResultsThe animal was weaned from ventilation after 5 h and kept on spontaneous breathing. The animal regained full consciousness, demonstrated early signs of sensory recovery, and restored brain functions. ConclusionPending further confirmatory studies, a phrenic-sparing cephalic reanastomosis with spinal cord fusion using fusogens has clarified the technical aspects of the procedure. A head replantation model with complete vascular cannulation was developed, resulting in the recovery of spontaneous breathing and brain functions.

bioengineering↗

bioRxiv2024

MatriCom: a scRNA-Seq data mining tool to infer ECM-ECM and cell-ECM communication systems

The ECM is a complex and dynamic meshwork of proteins that forms the framework of all multicellular organisms. Protein interactions within the ECM are critical to building and remodeling the ECM meshwork, while interactions between ECM proteins and cell surface receptors are essential for the initiation of signal transduction and the orchestration of cellular behaviors. Here, we report the development of MatriCom, a web application (https://matrinet.shinyapps.io/matricom) and a companion R package (https://github.com/Izzilab/MatriCom), devised to mine scRNA-Seq datasets and infer communications between ECM components and between different cell populations and the ECM. To impute interactions from expression data, MatriCom relies on a unique database, MatriComDB, that includes over 25,000 curated interactions involving matrisome components, with data on 80% of the [~]1,000 genes that compose the mammalian matrisome. MatriCom offers the option to query open-access datasets sourced from large sequencing efforts (Tabula Sapiens, The Human Protein Atlas, HuBMAP) or to process user-generated datasets. MatriCom is also tailored to account for the specific rules governing ECM protein interactions and offers options to customize the output through stringency filters. We illustrate the usability of MatriCom with the example of the human kidney matrisome communication network. Last, we demonstrate how the integration of 46 scRNA-Seq datasets led to the identification of both ubiquitous and tissue-specific ECM communication patterns. We envision that MatriCom will become a powerful resource to elucidate the roles of different cell populations in ECM-ECM and cell-ECM interactions and their dysregulations in the context of diseases such as cancer or fibrosis. ONE SENTENCE SUMMARYMatriCom is a web application devised to mine scRNA sequencing datasets to infer ECM-ECM and cell-ECM communication systems in the context of the diverse cell populations that constitute any tissue or organ.

systems biology↗

bioRxiv2024

Changes in the Public IgM Repertoire and its Idiotypic Connectivity in Alzheimer's Disease and Frontotemporal Dementia

Alzheimers disease (AD) and frontotemporal dementia (FTD) are prevalent neurodegenerative disorders. Early diagnosis is challenging due to the lack of definitive biomarkers and reliance on invasive procedures. Immune biomarkers, particularly those reflecting the interaction between the central nervous system (CNS) and the peripheral immune system, have shown promise for non-invasive detection through blood samples. This study investigates the reactivity of serum IgM and IgG from AD and FTD patients against a library of mimotopes representing public IgM reactivities in healthy donors. Serum samples from AD, FTD, and other neurodegenerative dementias (ND) and controls were tested on peptide microarrays. The samples were pooled to mitigate individual variability. The reactivity data were analyzed using graphs to represent the cross-reactivity networks. The analysis revealed distinct reactivity patterns for the studied groups. Public IgM reactivities showed significant correlations with neurodegenerative conditions, with AD and FTD exhibiting loss or gain of specific IgM reactivities. Graph analysis highlighted significant differences between disease and control groups in graph density, clustering, and assortativity parameters. Mimotopes of IgM reactivities lost in dementia, particularly in AD, exhibited significant homology to HCDR3 sequences of human antibodies. Furthermore, clusters of reactivities showed significant distinctions between AD and FTD, with IgG reactivities providing additional differentiation. Several self-proteins related to neurodegeneration proved to have sequences homologous to disease-associated mimotopes. Interestingly, the beta-propeller signature sequence YWTD found in ApoEs receptor LRP1 proved a characteristic epitope for IgG in FTD but not AD. At the same time, the respective public |gM mimotope YWTDSSR coincides with a highly conserved sequence in many microorganisms and sequences found in human HCDR3. Thus, the public IgM repertoire, characterized by its broad reactivity and inherent autoreactivity, offers valuable insights into the immunological alterations in neurodegenerative diseases. The study supports the potential of IgM and IgG reactivity profiles as another compartment of non-invasive biomarkers for early diagnosis and differentiating AD and FTD.

immunology↗

bioRxiv2024

ProToDeviseR: an automated protein topology scheme generator

MotivationAmino acid sequence characterization is a fundamental part of virtually any protein analysis, and creating concise and clear protein topology schemes is of high importance in proteomics studies. Although numerous databases and prediction servers exist, it is challenging to incorporate data from various, and sometimes contending, resources into a publication-ready scheme. ResultsHere, we present the Protein Topology Deviser R package (ProToDeviseR) for the automatic generation of protein topology schemes from database accession numbers, raw results from multiple prediction servers, or a manually prepared table of features. The application offers a graphical user interface, implemented in R Shiny, hosting an enhanced version of Pfams domains generator for the rendering of visually appealing schemes. Results show that ProToDeviseR can easily and quickly generate topology schemes by interrogating UniProt or NCBI GenPept databases and elegantly combine features from various resources. AvailabilitySource code (https://github.com/izzilab/protodeviser) is available under GPLv3 license; the tool is also accessible for online use (https://matrinet.shinyapps.io/protodeviser/), without the need of installation.

bioinformatics↗

bioRxiv2022

Nutrient and salt depletion synergistically boosts glucose metabolism in individual Escherichia coli cells

The interaction between a cell and its environment shapes fundamental intracellular processes such as cellular metabolism. In most cases growth rate is treated as a proximal metric for understanding the cellular metabolic status. However, changes in growth rate might not reflect metabolic variations in individuals responding to environmental fluctuations. Here we use single-cell microfluidics-microscopy combined with transcriptomics, proteomics and mathematical modelling to quantify the accumulation of glucose within Escherichia coli cells. In contrast to the current consensus, we reveal that environmental conditions which are comparatively unfavourable for growth, where both nutrients and salinity are depleted, increase glucose accumulation rates in individual bacteria and population subsets. We find that these changes in metabolic function are underpinned by variations at the translational and posttranslational level but not at the transcriptional level and are not dictated by changes in cell size. The metabolic response-characteristics identified greatly advance our fundamental understanding of the interactions between bacteria and their environment and have important ramifications when investigating cellular processes where salinity plays an important role.

microbiology↗

bioRxiv2020

APEX2 proximity biotinylation reveals protein dynamics triggered by B cell receptor activation

Successful B cell activation, critical for high-affinity antibody production, is controlled by the B cell antigen receptor (BCR). However, we still lack a comprehensive protein-level view of the very dynamic multi-branched cellular events triggered by antigen binding. Here, we employed APEX2 proximity biotinylation to study antigen-induced changes, 5-15 min after receptor activation, at the vicinity of the plasma membrane lipid rafts, wherein BCR enriches upon activation. The data reveals dynamics of signaling proteins, as well as various players linked to the subsequent processes, such as actin cytoskeleton remodelling and endocytosis. Interestingly, our differential expression analysis identified dynamic responses in various proteins previously not linked to early B cell activation. We demonstrate active SUMOylation at the sites of BCR activation in various conditions and report its functional role in BCR signaling through Akt and MAPK axes.

immunology↗

bioRxiv2020

Prefrontal neural dynamics for behavioral decisions and attentional control

Complex neural dynamics in the prefrontal cortex contribute to context-dependent decisions and attentional competition. To analyze these dynamics, we apply demixed principal component analysis to activity of a primate prefrontal cell sample recorded in a cued target detection task. The results track dynamics of cue and object coding, feeding into movements along a target present-absent decision axis in a low-dimensional subspace of population activity. For a single stimulus, object and cue coding are seen mainly in the contralateral hemisphere. Later, a developing decision code in both hemispheres may reflect interhemispheric communication. With a target in one hemifield and a competing nontarget in the other, each hemisphere initially encodes the contralateral object, but finally, decision coding is dominated by the task-relevant target. These findings further suggest that exchange of information between hemispheres plays a key role when attentional competition resolves. Tracking complex neural events in a low-dimensional activity subspace illuminates integration of neural codes towards task-appropriate behavior, comprising a building block of learned task structure in the prefrontal cortex. AUTHOR SUMMARYFlexible adaptive processing of information is integral for everyday goal-directed behavior. To unravel dynamic representation of task-relevant information, we analyzed population activity of a primate prefrontal cell sample in a cued target detection task. In a low-dimensional neural subspace, with separate axes for cue, object identity and decision, trajectories showed initial coding of cue and object in the contralateral hemisphere, followed by coding of the behavioral decision across both hemispheres. With target and nontarget stimuli in opposite hemifields, the data suggest initial coding of the contralateral object in each hemisphere. Object coding is then rapidly shut off for the nontarget, and followed by bilateral coding of the target decision. The results bring detailed insight into task structure and information flow within and between the two frontal lobes as a decision is made and attentional competition is resolved.

neuroscience↗

bioRxiv2019

Missing-In-Metastasis / Metastasis Suppressor 1 modulates B cell receptor signaling, B cell metabolic potential and T cell-independent immune responses.

Efficient generation of antibodies by B cells is one of the prerequisites of protective immunity. B cell activation by cognate antigens via B cell receptors (BCR), or pathogen-associated molecules through pattern-recognition receptors, such as Toll-like receptors (TLRs), leads to transcriptional and metabolic changes that ultimately transform B cells into antibody producing plasma cells or memory cells. BCR signaling and a number of steps downstream of it rely on coordinated action of cellular membranes and the actin cytoskeleton, tightly controlled by concerted action of multiple regulatory proteins, some of them exclusive to B cells. Here, we dissect the role of Missing-In-Metastasis (MIM), or Metastasis suppressor 1 (MTSS1), a cancer-associated membrane and actin cytoskeleton regulating protein, in B cell-mediated immunity by taking advantage of MIM knockout mouse strain. We show undisturbed B cell development and largely normal composition of B cell compartments in the periphery. Interestingly, we found that MIM-/- B cells are defected in BCR signaling in response to surface-bound antigens but, on the other hand, show increased metabolic activity after stimulation with LPS or CpG. In vivo, MIM knockout animals exhibit impaired IgM antibody responses to immunization with T cell-independent antigen. This study provides the first comprehensive characterization of MIM in B cells, demonstrates its regulatory role for B cell-mediated immunity, as well as proposes new functions for MIM in tuning receptor signaling and cellular metabolism, processes which may also contribute to the poorly understood functions of MIM in cancer.

immunology↗

bioRxiv2019

Fast targeting of antigen and surface-derived MHCII into degradative compartments implies endosomal prewiring for antigen presentation in B cells.

In order to mount high-affinity antibody responses, B cells internalise specific antigens and process them into peptides loaded onto MHCII for presentation to TO_SCPLOWHC_SCPLOW cells. While the biochemical principles of antigen processing and MHCII loading have been well dissected, how the endosomal vesicle system is wired to enable these specific functions remains much less studied. Here, we performed a systematic microscopy-based analysis of antigen trafficking in B cells to reveal its route to the MHCII peptide-loading compartment (MIIC). Surprisingly, we detected fast targeting of internalised antigen into peripheral acidic compartments that possessed the hallmarks of MIIC and also showed degradative capacity. In these vesicles, internalised antigen converged rapidly with membrane-derived MHCII and partially overlapped with Cathepsin-S and H2-M, both required for peptide loading. These early compartments appeared heterogenous and atypical as they contained a mixture of both early and late markers, indicating specialized endosomal route. Together, our data suggests that, in addition to previously-reported perinuclear late endosomal MIICs, antigen processing and peptide loading could start already in these specialized early peripheral acidic vesicles (eMIIC) to support fast peptide-MHCII presentation.

immunology↗