- by Pop, R. T., Hsieh, P.-H., Belova, T., Mathelier, A., Kuijjer, M. L.The emergence of high-throughput omics technologies has resulted in their wide application to cancer studies, greatly increasing our understanding of the disruptions occurring at different molecular levels. The role of gene regulation as a core driver of biological processes and its role in the development and progression of cancer has been well established. Transcriptional regulation, a crucial aspect of gene regulation, can be represented as a network of interactions between regulators (such as transcription factors) and their target genes. These […]
- by Lent, P. v., Bunkova, O., Planken, L., Schmitz, J., Abeel, T.Motivation: Metabolic kinetic models are widely used to model biological systems. Despite their widespread use, it remains challenging to parameterize these Ordinary Differential Equations (ODE) for large scale kinetic models. Recent work on neural ODEs has shown the potential for modeling time-series data using neural networks, and many methodological developments in this field can similarly be applied to kinetic models. Results: We have implemented a simulation and training framework for Systems Biology Markup Language (SBML) models using JAX/Diffrax, which we […]
- by Leray, X., Morales, J., Trefier, A., Leon, K., Bourquard, T., Musnier, A., Pecnard, E., Drobecq, L., Boulben, S., Azzopardi, N., Coulaud, R., Ouchene, H., Jaszczyszyn, Y., Reiter, E., Guillou, F., Pellissier, L. P., Poupon, A., Yvinec, R., Crepieux, P.The effects of hormone stimulation on the cell translational profile remain poorly understood. Here, using polysome profiling combined to RNA sequencing, we analyzed the translational response to follicle-stimulating hormone (FSH) of primary rat Sertoli cells, that exhibit an active anabolic activity regulated by reproductive hormones in the male gonad. We first established that mRNA distribution to polysomes follows a bimodal pattern, with 15% of mRNAs enriched in polysomes and exhibiting high expression. Critically, this basal polysomal enrichment had a major […]
- by Lu, F., Zlobina, K., Baniya, P., Li, H., Rondoni, N. A., Asefifeyzabadi, N., Hee, W. S., Tebyani, M., Schorger, K., Franco, C., Bagood, M., Teodorescu, M., Rolandi, M., Isseroff, R., Gomez, M.Advancements in bioelectronic sensors and actuators have paved the way for real-time monitoring and control of wound healing progression. Real-time monitoring allows for precise adjustment in treatment strategies that align with an individual's unique biological response. However, due to the complexities of human-drug interactions and a lack of predictive models it is challenging to determine just how one should adjust drug dosage to achieve the desired biological response. This work proposes an adaptive closed-loop control framework that integrates deep learning, […]
- by Kristofori, P., Braun, S., Busch, A., Zarnack, K., Koenig, J., Legewie, S., Li, C.Alternative splicing of pre-mRNA is a fundamental step in human gene regulation and aberrant slic-ing is tightly linked to diseases including cancer. Various splicing events, such as alternative exon (AE) choice and intron retention (IR), are controlled by a common molecular machinery, the spliceosome. However, it remains elusive how the regulation of spliceosome activity coordinately affects these splicing decisions. Here, we analyze a large-scale mutagenesis screen and genome-wide RNA sequencing data to show that IR and AE choice are tightly […]
- by Keele, G. R., Dou, Y., Kodikara, S. P., Jeffery, E. D., Bai, D., Paulo, J. A., Gygi, S. P., Tian, X., Zhang, T.Aging results in a progressive decline in physiological function due to the deterioration of essential biological processes, such as transcription and RNA splicing, ultimately increasing mortality risk. Although proteomics is emerging as a powerful tool for elucidating the molecular mechanisms of aging, existing studies are constrained by limited proteome coverage and only observe a narrow range of lifespan. To overcome these limitations, we integrated the Orbitrap Astral Mass Spectrometer with the multiplex tandem mass tag (TMT) technology to profile the […]
- by Wu, Q. C., Swaminathan, A., Winward, A., Lalonde, L., Hwang, Y., Littman, N., Socolovsky, M., Klein, A. M.Feedback control of erythropoiesis exemplifies conflicting goals in tissue homeostasis: maintaining fast reactivity to stress while minimizing proliferative burden on progenitors in the steady state. Here we show that these conflicting goals are tuned through the combinatorial action of cytokines. We find that IL-17A, a pro-inflammatory cytokine, mediates striking synergism with the negative feedback signal erythropoietin (Epo) in vivo, accelerating the erythropoietic response to hypoxia. A model of erythropoietic control shows increased reactivity may occur through two cell circuit designs, […]
- by Sil, P., Mitra, S., Martin, O. C., Samal, A.Random Boolean networks (RBNs) have been widely explored as models for understanding complex systems, in particular gene regulatory networks (GRNs). Stability (order) and instability (chaos), critical characteristics of any dynamic system, have naturally been a central focus in RBN research. Several measures have previously been introduced to assess stability, e.g., via damage spreading or via statistical properties of attractors such as their number, lengths or basin sizes. Undoubtedly, network topology plays an important role in shaping the dynamics of RBN. […]
- by Roberts, P. A., Thomas, C. N., Bellamy Plaice, G., Roberts, J. A., Jones, M.-C., Andrews, J. W., Hill, L. J.Purpose: Wet age-related macular degeneration (AMD) causes vision loss when vascular endothelial growth factor (VEGF) stimulates blood vessel growth into the light-sensitive retina. Anti-VEGF treatments such as ranibizumab are currently administered to treat wet AMD via intravitreal injections, which are unpleasant, expensive and risk complications. We explored the efficacy of topically administered ranibizumab, with cell penetrating peptides (CPPs). Methods: Ex vivo pig eyes were divided into 3 groups and treated with 1. topical or 2. intravitreal ranibizumab and CPP, or […]
- by Lu, F., Zlobina, K., Osorio, S., Yang, H., Nava, A., Bagood, M., Rolandi, M., Isseroff, R., Gomez, M.Wound healing is a complex, nonlinear biological process that involves multiple stages and relies on various cellular and biochemical interactions. Accurately predicting the healing stages of wounds is crucial for effective treatments, as it allows clinicians to intervene appropriately based on the current state of healing. However, due to the inherent nonlinear dynamics of wound healing, traditional linear methods often fall short in capturing the nuanced dependencies and temporal interactions within the healing process.
- by Argyris, G., Zeegelaar, R. A., Post, J. N.Tissue engineering protocols achieve building miniature hearts but mechanisms determining cell differentiation still need to be fully understood and optimized. In this study, we present a gene regulatory network (GRN) that describes the differentiation of committed cardiomyocytes towards ventricular or atrial cardiomyocytes. The GRN is coupled with Boolean dynamics and steady state analysis shows steady states which agree with the experimental expression of marker genes. Our Boolean model extends earlier work on a model describing the first and second heart […]
- by Haase, M., Comlekoglu, T., Petrucciani, A., Sego, T. J., Peirce, S. M., Blemker, S.Skeletal muscle regeneration is crucial for maintaining muscle health and mobility, making it a key research focus. Common experimental models of muscle injury used to study this process in vivo include cardiotoxin injury (CTX), freeze-induced (FI) injury, and eccentric contraction (EC) injury. While the response to injury varies across these models, these variations are often overlooked in experimental designs. The cellular dynamics throughout the time course of muscle regeneration differ significantly between these injury types, presenting challenges for both experimental […]
- by Lomagno, A., Yusuf, I., Tosadori, G., Bonanomi, D., Mauri, P., Di Silvestre, D.We present here the Co-expressed Protein-Protein Interactions (CoPPIs) algorithm. In addition to minimizing correlation-causality imbalance and contextualizing PPIs to the investigated systems, it combines PPIs and protein co-expression networks to identify differentially correlated functional modules. To test CoPPIs, we processed a set of proteomic profiles from different brain areas of controls and subjects affected by idiopathic Parkinsons disease or carrying a GBA1 mutation. Its robustness was supported by the extraction of functional modules, related to translation and mitochondria, whose involvement […]
- by Narayanan, B., Jiang, W., Wang, S., Saez-Saez, J., Weilandt, D. R., Masid, M., Hesselberg-Thomsen, V., Borodina, I., Hatzimanikatis, V., Miskovic, L.The use of kinetic models of metabolism in design-build-learn-test cycles is limited despite their potential to guide and accelerate the optimization of cell factories. This is primarily due to difficulties in constructing kinetic models capable of capturing the complexities of the fermentation conditions. Building on recent advances in kinetic-model-based strain design, we present the rational metabolic engineering of an S. cerevisiae strain designed to overproduce p-coumaric acid (p-CA), an aromatic amino acid with valuable nutritional and therapeutic applications. To this […]
- by NALLUR, G. N.In a proteomics investigation of a Parkinsons disease [PD] cell model, a panel of 7 proprietary PINTAC peptides deployed in an in vitro phenotypic screen in SH-SY5Y cells treated with 6-OHDA identified 2 shorter variants of PERK protein kinase. One of the PERK variants, which is SUMOylated, associates in vitro with phosphorylated EIF2 alpha and its ubiquitinated isoforms, which also involves another PERK substrate. PINTACs revealed the presence of multiple post-translational modifications [PTMs] of MAPK1 in presence of OHDA. A […]
- by Villette, R., Ortis Sunyer, J., Novikova, P., Aho, V. T. E., Petrov, V., Hickl, O., Bhanu Busi, S., De Rudder, C., Kunath, B. J., Heintz-Buschart, A., Trezzi, J.-P., Halder, R., Jaeger, C., Lebrun, L. E., Daujeumont, A., Schade, S., Janzen, A. E., Jehmlich, N., von Bergen, M., Laczny, C. C., May, P., Trenkwalder, C., Oertel, W., Mollenhauer, B., Wilmes, P.Parkinsons disease (PD) is associated with gut microbiome shifts, but the functional consequences remain unclear. Here, we use an integrated multi-omics approach to compare the gut microbiomes of individuals with PD and prodromal PD as well as healthy individuals. After analyzing each omics, meta-metabolomic was selected to inform the analysis as it represents the most discriminatory and robust ome. We identified 11 metabolites that were differentially abundant between the groups, amongst which {beta}-glutamate was increased in PD and prodromal PD, […]
- by Lamba, R., Paguntalan, A. M., Petrov, P., Izzi, V., Naba, A.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 […]
- by Rozum, J. C., Sineath, W. D., Kim, D. N., Bohutskyi, P., Johnson, C. G., Evans, J. E., Pollock, D. D., QIAN, W.-J., Cheung, M. S., Wu, R., Feng, S.Bacteriophage auxiliary metabolic genes (AMGs) alter host metabolism by hijacking reactions. Previous studies used functional annotations to infer AMG impacts, but how these propagate and interact to affect global metabolism and phage production remains understudied. We demonstrate the first integration of AMGs and phage assembly into a genome-scale metabolic model, using P-HM2 infection of Prochloroccocus marinus MED4 as a test system. Our model predicts that 17 directly hijacked reactions substantially impact over 30% of the metabolism, including carbon fixation, photosynthesis, […]
- A detailed kinetic model of Eastern equine encephalitis virus replication in a susceptible host cellby Larkin, C. I., Dunn, M. D., Shoemaker, J. E., Klimstra, W. B., Faeder, J. R.Eastern equine encephalitis virus (EEEV) is an arthropod-borne, positive-sense RNA alphavirus posing a substantial threat to public health. Unlike similar viruses such as SARS-CoV-2, EEEV replicates efficiently in neurons, producing progeny viral particles as soon as 3-4 hours post-infection. EEEV infection, which can cause severe encephalitis with a human mortality rate surpassing 30%, has no licensed, targeted therapies, leaving patients to rely on supportive care. Although the general characteristics of EEEV infection within the host cell are well-studied, it remains […]
- by Gardner, A. L., Zheng, L., Howland, K. K., Saunders, A., Ramirez, A., Parker, P., Iloegbunam, C., Morgan, D., Jost, T. A., Brock, A.Cell-cell fusion is a tightly controlled process in the human body known to be involved in fertilization, placental development, muscle growth, bone remodeling, and viral response. Fusion between cancer cells results first in a whole-genome doubled state, which may be followed by the generation of aneuploidies; these genomic alterations are known drivers of tumor evolution. The role of cell-cell fusion in cancer progression and treatment response has been understudied due to limited experimental systems for tracking and analyzing individual fusion […]
Mass spectrometry websites, social media, journal feeds, and other links and items of interest to the mass spectrometry community.
