Biology subjects

Soliman, S.

Publications and source records attributed to Soliman, S..

9 recordsLinked to original sources

bioRxiv2026

TabularQual: A spreadsheet-based format for annotating and curating logical models in SBML-qual

Logical models are widely used to study regulatory and signaling systems, yet their reuse, annotation, and exchange across tools remain challenging. Although SBML Level 3 Qualitative Models (SBML-qual) provides a standard representation, its XML-based syntax is difficult to inspect and edit directly. Here we introduce TabularQual, a spreadsheet-based, community-driven representation for Boolean and multi-valued logical models, together with a bidirectional converter between spreadsheets and SBML-qual. The converter is accessible programmatically and via a web interface to support diverse user workflows. We further describe two integration strategies that enable existing modeling tools to operate with TabularQual, either through SBML-qual exchange or via direct support. Case studies using the Stress Knowledge Map and CaSQ demonstrate how this integration supports model construction, curation, and reuse. TabularQual provides a practical bridge between human-readable model representations and standardized executable formats, supporting reproducibility, interoperability, and community-driven model development.

systems biology↗

bioRxiv2023

Integrated spatial protein and RNA analysis on the same section using MICS technology

Spatial Biology has evolved from the molecular characterization of microdissected cells to high throughput spatial RNA and protein expression analysis at scale. The main limitation of spatial technologies so far is the inability to resolve protein and RNA information in the same histological section. Here, we report for the first time the integration of highly multiplexed RNA and protein detection on the same tissue section. We developed a new, automated, spatial RNA detection method (RNAsky), which is based on targeted rolling circle amplification and iterative staining. We combine RNAsky with MACSima Imaging Cyclic Staining (MICS) based protein analysis and show compatibility with subsequent standard hematoxylin and eosin (H&E) staining. Using both, open-source tools and our recently developed software suite MACS(R) iQ View, we demonstrate our multiomics MICS workflow by characterizing key immune-oncology markers at subcellular resolution across normal and diseased tissues.

molecular biology↗

bioRxiv2023

Hybrid computational modeling highlights reverse Warburg effect in breast cancer-associated fibroblasts

Cancer-associated fibroblasts (CAFs) are key players of the tumor microenvironment (TME) involved in cancer initiation, progression, and resistance to therapy. These cells exhibit aggressive phenotypes affecting, among others, extracellular matrix remodeling, angiogenesis, immune system modulation, tumor growth, and proliferation. CAFs phenotypic changes appear to be associated with metabolic alterations, notably a reverse Warburg effect that may drive fibroblasts transformation. However, its precise molecular mechanisms and regulatory drivers are still under investigation. Deciphering the reverse Warburg effect in breast CAFs may contribute to a better understanding of the interplay between TME and tumor cells, leading to new treatment strategies. In this regard, dynamic modeling approaches able to span multiple biological layers are essential to capture the emergent properties of various biological entities when complex and intertwined pathways are involved. This work presents the first hybrid large-scale computational model for breast CAFs covering major cellular signaling, gene regulation, and metabolic processes. It was generated by combining an asynchronous cell- and disease-specific regulatory Boolean model with a generic core metabolic network leveraging both data-driven and manual curation approaches. This model reproduces the experimentally observed reverse Warburg effect in breast CAFs and further identifies Hypoxia-Inducible Factor 1 (HIF-1) as its key molecular driver. Targeting HIF-1 as part of a TME-centered therapeutic strategy may prove beneficial in the treatment of breast cancer by addressing the reverse Warburg effect. Such findings in CAFs, considering our previously published results in rheumatoid arthritis synovial fibroblasts, point to a common HIF-1-driven metabolic reprogramming of fibroblasts in breast cancer and rheumatoid arthritis. All analyses are compiled and thoroughly annotated in Jupyter notebooks and R scripts available on a GitLab repository (https://gitlab.com/genhotel/breast-cafs-reverse-warburg-effect) and a Zenodo permanent archive [1].

systems biology↗

bioRxiv2023

A large-scale Boolean model of the Rheumatoid Arthritis Fibroblast-Like Synoviocytes predicts drug synergies in the arthritic joint

Rheumatoid arthritis (RA) is a complex autoimmune disease with an unknown aetiology. However, rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) play a significant role in initiating and perpetuating destructive joint inflammation by expressing immuno-modulating cytokines, adhesion molecules, and matrix remodelling enzymes. In addition, RA-FLS are primary drivers of inflammation, displaying high proliferative rates and an apoptosis-resistant phenotype. Thus, RA-FLS-directed therapies could become a complementary approach to immune-directed therapies by predicting the optimal conditions that would favour RA-FLS apoptosis, limit inflammation, slow the proliferation rate and minimise bone erosion and cartilage destruction. In this paper, we present a large-scale Boolean model for RA-FLS that consists of five submodels focusing on apoptosis, cell proliferation, matrix degradation, bone erosion and inflammation. The five phenotype-specific submodels can be simulated independently or as a global model. In-silico simulations and perturbations reproduced the expected biological behaviour of the system under defined initial conditions and input values. The model was then used to mimic the effect of mono or combined therapeutic treatments and predict novel targets and drug candidates through drug repurposing analysis.

systems biology↗

bioRxiv2022

A versatile and interoperable computational framework for the analysis and modeling of COVID-19 disease mechanisms

The COVID-19 Disease Map project is a large-scale community effort uniting 277 scientists from 130 Institutions around the globe. We use high-quality, mechanistic content describing SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing. Community-driven and highly interdisciplinary, the project is collaborative and supports community standards, open access, and the FAIR data principles. The coordination of community work allowed for an impressive step forward in building interfaces between Systems Biology tools and platforms. Our framework links key molecules highlighted from broad omics data analysis and computational modeling to dysregulated pathways in a cell-, tissue- or patient-specific manner. We also employ text mining and AI-assisted analysis to identify potential drugs and drug targets and use topological analysis to reveal interesting structural features of the map. The proposed framework is versatile and expandable, offering a significant upgrade in the arsenal used to understand virus-host interactions and other complex pathologies.

systems biology↗

bioRxiv2022

Metabolic Reprogramming in Rheumatoid Arthritis Synovial Fibroblasts: a Hybrid Modeling Approach

Rheumatoid Arthritis (RA) is an autoimmune disease characterized by a highly invasive pannus formation consisting mainly of synovial fibroblasts (RASFs). This pannus leads to cartilage, bone and soft tissue destruction in the affected joint. RASFs activation is associated with metabolic alterations resulting from dysregulation of extracellular signals transduction and gene regulation machinery. Deciphering the intricate mechanisms at the origin of this metabolic reprogramming may provide significant insight into RASFs involvement in RAs pathogenesis and offer new therapeutic strategies. Qualitative and quantitative dynamic modeling can address some of these features, but hybrid models represent a real asset in their ability to span multiple layers of biological machinery. This work presents the first hybrid RASF model: the combination of a cell-specific qualitative regulatory network with a global metabolic network. The automated framework for hybrid modeling exploits the regulatory networks trap-spaces as additional constraints on the metabolic networks. Subsequent flux balance analysis allows assessment of RASFs regulatory outcomes impact on their metabolic flux distribution. The hybrid RASF model simulates the experimentally observed metabolic reprogramming induced by signaling and gene regulation in RASFs. Simulations also enable further hypotheses on the potential reverse Warburg effect in RA. RASFs may undergo metabolic reprogramming to turn into "metabolic factories", producing high levels of energy-rich fuels and nutrients for neighboring demanding cells through the crucial role of HIF1. Author SummaryWe successfully built the first large-scale hybrid dynamical model for human Rheumatoid Arthritis Synovial Fibroblasts (RASFs) including signaling, gene regulation and metabolism. We used a state-of-the-art molecular map for upstream signaling and gene regulation, the tool CaSQ to infer a large-scale Boolean model, and a genome-scale metabolic model. Trap-spaces of the Boolean asynchronous model were used to infer additional metabolic constraints on the metabolic network for subsequent flux balance analysis. This method allowed us to study the impact of various regulatory initial conditions on RASFs metabolic fluxes distribution. Our model successfully reproduces the metabolic reprogramming of RASFs which shift their ATP production from oxidative pathways to glycolysis, highlighting the key role of HIF1 in this process. Our findings allow us to hypothesize a reverse Warburg relationship occurring between RASFs and other RA joint cells. Similarly to tumor microenvironments fibroblasts, RASFs would undergo a metabolic switch and reprogram their metabolism to adapt to their hypoxic environment and provide crucial metabolic intermediates to neighboring cells to sustain their inflammatory activity.

systems biology↗

bioRxiv2021

Mucoricin is a Ricin-Like Toxin that is Critical for the Pathogenesis of Mucormycosis

Fungi of the order Mucorales cause mucormycosis, a lethal infection with an incompletely understood pathogenesis. We now demonstrate that Mucorales fungi produce a toxin that plays a central role in virulence. Polyclonal antibodies against this toxin inhibit its ability to damage human cells in vitro, and prevent hypovolemic shock, organ necrosis, and death in mice with mucormycosis. RNAi inhibition of the toxin in Rhizopus delemar, compromises the ability of the fungus to damage host cells and attenuates virulence in mice. This 17 kDa toxin has structural and functional features of the plant toxin, ricin, including the ability to inhibit protein synthesis by its N-glycosylase activity, the existence of a motif that mediates vascular leak, and a lectin sequence. Antibodies against the toxin inhibit R. delemar- or toxin-mediated vascular permeability in vitro and cross-react with ricin. A monoclonal anti-ricin B chain antibody binds to the toxin and also inhibits its ability to cause vascular permeability. Therefore, we propose the name "mucoricin" for this toxin. Not only is mucoricin important in the pathogenesis of mucormycosis but our data suggest that a ricin- like toxin is produced by organisms beyond the plant and bacterial kingdoms. Importantly, mucoricin should be a promising therapeutic target.

microbiology↗

bioRxiv2019

Tagging allows faithful tracing of expression and enhances biochemical detection of Ran Binding Protein 9 in vivo.

The lack of tools to reliably detect RanBP9 in vivo has significantly hampered progress in understanding the biological functions of this scaffold protein. We report here the generation of a novel mouse strain, RanBP9-TT, in which the endogenous protein is fused with a double (V5-HA) epitope tag at the C-terminus. We show that the double tag does not interfere with the essential functions of RanBP9. In contrast to RanBP9 constitutive knock-out animals, RanBP9-TT mice are viable, fertile and do not show any obvious phenotype. The V5-HA tag allows unequivocal detection of RanBP9 both by IHC and WB. Importantly, immunoprecipitation and mass spectrometry analyses reveal that the tagged protein pulls down known interactors of wild type RanBP9. Thanks to the increased detection power, we are also unveiling a novel interaction with Nucleolin, a prominent nucleolar protein. In summary, we report the generation of a new mouse line in which RanBP9 expression and interactions can be reliably studied by the use of commercially available tag antibodies. The use of this line will help to overcome some of the existing limitations in the study of RanBP9 and potentially reveal novel functions of this protein in vivo such as those linked to Nucleolin.

bioengineering↗

bioRxiv2017

Morphological Alternations of Intraepithelial and Stromal Telocytes in Response to Salinity Challenges

Summary statementThe article represent an experimental study in which we investigated the effect of the ssalinty on the communicating cells (telocytes) and their target cells including chloride, stem, Rodlet cells, myoblasts\n\nAbstractTelocyte is a communicating cell established relations to various types of cells. Few experimental studies are performed on telocytes. The current study investigated responce of telocytes to salinity stress in relations to osmoregualtory, immune and stem cells. We exposed Common carp to salinity level 0.2, 6, 10, 14 ppt. Gill samples were fixed and processed for microscopic and TEM. Two types of telocytes were identified: intraepithelial and stromal telocytes. Intraepithelial telocytes comprised the cellular lining of the lymph spaces where they shed the secretory vesicles. Stromal telocytes shed their secretory vesicles in the secondary circulatory vessels. Telocyte enlarged and exhibited high secretory activities. They exert their effect either by direct contact or by paracrine mode. In sanity treated samples, chloride cells enlarged and the mitochondria became cigar-shaped. pavement cells enlarged and micro-ridges elongated. Stromal telocytes established contact with stem cell and skeletal myoblast. Macrophages and Rodlet cells increased in number. In conclusion, intraepithelial and stromal responded to salinity stress by activation of cellular signaling. They play a major role in osmoregulation, immunity, and regeneration.

zoology↗