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Journals NPJ Systems Biology and Applic...

NPJ Systems Biology and Applications

https://read.qxmd.com/read/38527998/transcriptome-free-energy-can-serve-as-a-dynamic-patient-specific-biomarker-in-acute-myeloid-leukemia
#1
JOURNAL ARTICLE
Lisa Uechi, Swetha Vasudevan, Daniela Vilenski, Sergio Branciamore, David Frankhouser, Denis O'Meally, Soheil Meshinchi, Guido Marcucci, Ya-Huei Kuo, Russell Rockne, Nataly Kravchenko-Balasha
Acute myeloid leukemia (AML) is prevalent in both adult and pediatric patients. Despite advances in patient categorization, the heterogeneity of AML remains a challenge. Recent studies have explored the use of gene expression data to enhance AML diagnosis and prognosis, however, alternative approaches rooted in physics and chemistry may provide another level of insight into AML transformation. Utilizing publicly available databases, we analyze 884 human and mouse blood and bone marrow samples. We employ a personalized medicine strategy, combining state-transition theory and surprisal analysis, to assess the RNA transcriptome of individual patients...
March 25, 2024: NPJ Systems Biology and Applications
https://read.qxmd.com/read/38499572/making-drugs-from-t-cells-the-quantitative-pharmacology-of-engineered-t-cell-therapeutics
#2
JOURNAL ARTICLE
Daniel C Kirouac, Cole Zmurchok, Denise Morris
Engineered T cells have emerged as highly effective treatments for hematological cancers. Hundreds of clinical programs are underway in efforts to expand the efficacy, safety, and applications of this immuno-therapeutic modality. A primary challenge in developing these "living drugs" is the complexity of their pharmacology, as the drug product proliferates, differentiates, traffics between tissues, and evolves through interactions with patient immune systems. Using publicly available clinical data from Chimeric Antigen Receptor (CAR) T cells, we demonstrate how mathematical models can be used to quantify the relationships between product characteristics, patient physiology, pharmacokinetics and clinical outcomes...
March 18, 2024: NPJ Systems Biology and Applications
https://read.qxmd.com/read/38493227/a-robust-ultrasensitive-transcriptional-switch-in-noisy-cellular-environments
#3
JOURNAL ARTICLE
Eui Min Jeong, Jae Kyoung Kim
Ultrasensitive transcriptional switches enable sharp transitions between transcriptional on and off states and are essential for cells to respond to environmental cues with high fidelity. However, conventional switches, which rely on direct repressor-DNA binding, are extremely noise-sensitive, leading to unintended changes in gene expression. Here, through model simulations and analysis, we discovered that an alternative design combining three indirect transcriptional repression mechanisms, sequestration, blocking, and displacement, can generate a noise-resilient ultrasensitive switch...
March 16, 2024: NPJ Systems Biology and Applications
https://read.qxmd.com/read/38491038/go2sum-generating-human-readable-functional-summary-of-proteins-from-go-terms
#4
JOURNAL ARTICLE
Swagarika Jaharlal Giri, Nabil Ibtehaz, Daisuke Kihara
Understanding the biological functions of proteins is of fundamental importance in modern biology. To represent a function of proteins, Gene Ontology (GO), a controlled vocabulary, is frequently used, because it is easy to handle by computer programs avoiding open-ended text interpretation. Particularly, the majority of current protein function prediction methods rely on GO terms. However, the extensive list of GO terms that describe a protein function can pose challenges for biologists when it comes to interpretation...
March 15, 2024: NPJ Systems Biology and Applications
https://read.qxmd.com/read/38459044/multivariate-canonical-correlation-analysis-identifies-additional-genetic-variants-for-chronic-kidney-disease
#5
JOURNAL ARTICLE
Amy J Osborne, Agnieszka Bierzynska, Elizabeth Colby, Uwe Andag, Philip A Kalra, Olivier Radresa, Philipp Skroblin, Maarten W Taal, Gavin I Welsh, Moin A Saleem, Colin Campbell
Chronic kidney diseases (CKD) have genetic associations with kidney function. Univariate genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with estimated glomerular filtration rate (eGFR) and blood urea nitrogen (BUN), two complementary kidney function markers. However, it is unknown whether additional SNPs for kidney function can be identified by multivariate statistical analysis. To address this, we applied canonical correlation analysis (CCA), a multivariate method, to two individual-level CKD genotype datasets, and metaCCA to two published GWAS summary statistics datasets...
March 9, 2024: NPJ Systems Biology and Applications
https://read.qxmd.com/read/38459043/data-driven-energy-landscape-reveals-critical-genes-in-cancer-progression
#6
JOURNAL ARTICLE
Juntan Liu, Chunhe Li
The evolution of cancer is a complex process characterized by stable states and transitions among them. Studying the dynamic evolution of cancer and revealing the mechanisms of cancer progression based on experimental data is an important topic. In this study, we aim to employ a data-driven energy landscape approach to analyze the dynamic evolution of cancer. We take Kidney renal clear cell carcinoma (KIRC) as an example. From the energy landscape, we introduce two quantitative indicators (transition probability and barrier height) to study critical shifts in KIRC cancer evolution, including cancer onset and progression, and identify critical genes involved in these transitions...
March 8, 2024: NPJ Systems Biology and Applications
https://read.qxmd.com/read/38453965/detecting-and-understanding-meaningful-cancerous-mutations-based-on-computational-models-of-mrna-splicing
#7
JOURNAL ARTICLE
Nicolas Lynn, Tamir Tuller
Cancer research has long relied on non-silent mutations. Yet, it has become overwhelmingly clear that silent mutations can affect gene expression and cancer cell fitness. One fundamental mechanism that apparently silent mutations can severely disrupt is alternative splicing. Here we introduce Oncosplice, a tool that scores mutations based on models of proteomes generated using aberrant splicing predictions. Oncosplice leverages a highly accurate neural network that predicts splice sites within arbitrary mRNA sequences, a greedy transcript constructor that considers alternate arrangements of splicing blueprints, and an algorithm that grades the functional divergence between proteins based on evolutionary conservation...
March 7, 2024: NPJ Systems Biology and Applications
https://read.qxmd.com/read/38453929/morphological-entropy-encodes-cellular-migration-strategies-on-multiple-length-scales
#8
JOURNAL ARTICLE
Yanping Liu, Yang Jiao, Qihui Fan, Xinwei Li, Zhichao Liu, Dui Qin, Jun Hu, Liyu Liu, Jianwei Shuai, Zhangyong Li
Cell migration is crucial for numerous physiological and pathological processes. A cell adapts its morphology, including the overall and nuclear morphology, in response to various cues in complex microenvironments, such as topotaxis and chemotaxis during migration. Thus, the dynamics of cellular morphology can encode migration strategies, from which diverse migration mechanisms can be inferred. However, deciphering the mechanisms behind cell migration encoded in morphology dynamics remains a challenging problem...
March 7, 2024: NPJ Systems Biology and Applications
https://read.qxmd.com/read/38448436/integration-of-graph-neural-networks-and-genome-scale-metabolic-models-for-predicting-gene-essentiality
#9
JOURNAL ARTICLE
Ramin Hasibi, Tom Michoel, Diego A Oyarzún
Genome-scale metabolic models are powerful tools for understanding cellular physiology. Flux balance analysis (FBA), in particular, is an optimization-based approach widely employed for predicting metabolic phenotypes. In model microbes such as Escherichia coli, FBA has been successful at predicting essential genes, i.e. those genes that impair survival when deleted. A central assumption in this approach is that both wild type and deletion strains optimize the same fitness objective. Although the optimality assumption may hold for the wild type metabolic network, deletion strains are not subject to the same evolutionary pressures and knock-out mutants may steer their metabolism to meet other objectives for survival...
March 6, 2024: NPJ Systems Biology and Applications
https://read.qxmd.com/read/38431714/sunset-yellow-protects-against-oxidative-damage-and-exhibits-chemoprevention-in-chemically-induced-skin-cancer-model
#10
JOURNAL ARTICLE
Saurabh Singh, Sarika Yadav, Celine Cavallo, Durgesh Mourya, Ishu Singh, Vijay Kumar, Sachin Shukla, Pallavi Shukla, Romil Chaudhary, Gyan Prakash Maurya, Ronja Lea Jennifer Müller, Lilly Rohde, Aradhana Mishra, Olaf Wolkenhauer, Shailendra Gupta, Anurag Tripathi
Skin cancer and other skin-related inflammatory pathologies are rising due to heightened exposure to environmental pollutants and carcinogens. In this context, natural products and repurposed compounds hold promise as novel therapeutic and preventive agents. Strengthening the skin's antioxidant defense mechanisms is pivotal in neutralizing reactive oxygen species (ROS) and mitigating oxidative stress. Sunset Yellow (SY) exhibits immunomodulatory characteristics, evidenced by its capacity to partially inhibit the secretion of proinflammatory cytokines, regulate immune cell populations, and modulate the activation of lymphocytes...
March 2, 2024: NPJ Systems Biology and Applications
https://read.qxmd.com/read/38429306/do-calcium-channel-blockers-applied-to-cardiomyocytes-cause-increased-channel-expression-resulting-in-reduced-efficacy
#11
JOURNAL ARTICLE
Karoline Horgmo Jæger, Verena Charwat, Samuel Wall, Kevin E Healy, Aslak Tveito
In the initial hours following the application of the calcium channel blocker (CCB) nifedipine to microtissues consisting of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), we observe notable variations in the drug's efficacy. Here, we investigate the possibility that these temporal changes in CCB effects are associated with adaptations in the expression of calcium ion channels in cardiomyocyte membranes. To explore this, we employ a recently developed mathematical model that delineates the regulation of calcium ion channel expression by intracellular calcium concentrations...
March 1, 2024: NPJ Systems Biology and Applications
https://read.qxmd.com/read/38418561/integrative-temporal-multi-omics-reveals-uncoupling-of-transcriptome-and-proteome-during-human-t-cell-activation
#12
JOURNAL ARTICLE
Harshi Weerakoon, Ahmed Mohamed, Yide Wong, Jinjin Chen, Bhagya Senadheera, Oscar Haigh, Thomas S Watkins, Stephen Kazakoff, Pamela Mukhopadhyay, Jason Mulvenna, John J Miles, Michelle M Hill, Ailin Lepletier
Engagement of the T cell receptor (TCR) triggers molecular reprogramming leading to the acquisition of specialized effector functions by CD4 helper and CD8 cytotoxic T cells. While transcription factors, chemokines, and cytokines are known drivers in this process, the temporal proteomic and transcriptomic changes that regulate different stages of human primary T cell activation remain to be elucidated. Here, we report an integrative temporal proteomic and transcriptomic analysis of primary human CD4 and CD8 T cells following ex vivo stimulation with anti-CD3/CD28 beads, which revealed major transcriptome-proteome uncoupling...
February 28, 2024: NPJ Systems Biology and Applications
https://read.qxmd.com/read/38383542/agent-based-modeling-of-the-prostate-tumor-microenvironment-uncovers-spatial-tumor-growth-constraints-and-immunomodulatory-properties
#13
JOURNAL ARTICLE
Maisa N G van Genderen, Jeroen Kneppers, Anniek Zaalberg, Elise M Bekers, Andries M Bergman, Wilbert Zwart, Federica Eduati
Inhibiting androgen receptor (AR) signaling through androgen deprivation therapy (ADT) reduces prostate cancer (PCa) growth in virtually all patients, but response may be temporary, in which case resistance develops, ultimately leading to lethal castration-resistant prostate cancer (CRPC). The tumor microenvironment (TME) plays an important role in the development and progression of PCa. In addition to tumor cells, TME-resident macrophages and fibroblasts express AR and are therefore also affected by ADT. However, the interplay of different TME cell types in the development of CRPC remains largely unexplored...
February 21, 2024: NPJ Systems Biology and Applications
https://read.qxmd.com/read/38374087/transomics2cytoscape-an-automated-software-for-interpretable-2-5-dimensional-visualization-of-trans-omic-networks
#14
JOURNAL ARTICLE
Kozo Nishida, Junichi Maruyama, Kazunari Kaizu, Koichi Takahashi, Katsuyuki Yugi
Biochemical network visualization is one of the essential technologies for mechanistic interpretation of omics data. In particular, recent advances in multi-omics measurement and analysis require the development of visualization methods that encompass multiple omics data. Visualization in 2.5 dimension (2.5D visualization), which is an isometric view of stacked X-Y planes, is a convenient way to interpret multi-omics/trans-omics data in the context of the conventional layouts of biochemical networks drawn on each of the stacked omics layers...
February 19, 2024: NPJ Systems Biology and Applications
https://read.qxmd.com/read/38365857/forum-on-immune-digital-twins-a-meeting-report
#15
REVIEW
Reinhard Laubenbacher, Fred Adler, Gary An, Filippo Castiglione, Stephen Eubank, Luis L Fonseca, James Glazier, Tomas Helikar, Marti Jett-Tilton, Denise Kirschner, Paul Macklin, Borna Mehrad, Beth Moore, Virginia Pasour, Ilya Shmulevich, Amber Smith, Isabel Voigt, Thomas E Yankeelov, Tjalf Ziemssen
Medical digital twins are computational models of human biology relevant to a given medical condition, which are tailored to an individual patient, thereby predicting the course of disease and individualized treatments, an important goal of personalized medicine. The immune system, which has a central role in many diseases, is highly heterogeneous between individuals, and thus poses a major challenge for this technology. In February 2023, an international group of experts convened for two days to discuss these challenges related to immune digital twins...
February 16, 2024: NPJ Systems Biology and Applications
https://read.qxmd.com/read/38360881/evaluation-of-single-sample-network-inference-methods-for-precision-oncology
#16
JOURNAL ARTICLE
Joke Deschildre, Boris Vandemoortele, Jens Uwe Loers, Katleen De Preter, Vanessa Vermeirssen
A major challenge in precision oncology is to detect targetable cancer vulnerabilities in individual patients. Modeling high-throughput omics data in biological networks allows identifying key molecules and processes of tumorigenesis. Traditionally, network inference methods rely on many samples to contain sufficient information for learning, resulting in aggregate networks. However, to implement patient-tailored approaches in precision oncology, we need to interpret omics data at the level of individual patients...
February 15, 2024: NPJ Systems Biology and Applications
https://read.qxmd.com/read/38351188/markermap-nonlinear-marker-selection-for-single-cell-studies
#17
JOURNAL ARTICLE
Wilson Gregory, Nabeel Sarwar, George Kevrekidis, Soledad Villar, Bianca Dumitrascu
Single-cell RNA-seq data allow the quantification of cell type differences across a growing set of biological contexts. However, pinpointing a small subset of genomic features explaining this variability can be ill-defined and computationally intractable. Here we introduce MarkerMap, a generative model for selecting minimal gene sets which are maximally informative of cell type origin and enable whole transcriptome reconstruction. MarkerMap provides a scalable framework for both supervised marker selection, aimed at identifying specific cell type populations, and unsupervised marker selection, aimed at gene expression imputation and reconstruction...
February 14, 2024: NPJ Systems Biology and Applications
https://read.qxmd.com/read/38346982/crop-gpa-an-integrated-platform-of-crop-gene-phenotype-associations
#18
JOURNAL ARTICLE
Yujia Gao, Qian Zhou, Jiaxin Luo, Chuan Xia, Youhua Zhang, Zhenyu Yue
With the increasing availability of large-scale biology data in crop plants, there is an urgent demand for a versatile platform that fully mines and utilizes the data for modern molecular breeding. We present Crop-GPA ( https://crop-gpa.aielab.net ), a comprehensive and functional open-source platform for crop gene-phenotype association data. The current Crop-GPA provides well-curated information on genes, phenotypes, and their associations (GPAs) to researchers through an intuitive interface, dynamic graphical visualizations, and efficient online tools...
February 12, 2024: NPJ Systems Biology and Applications
https://read.qxmd.com/read/38336968/mitigating-non-genetic-resistance-to-checkpoint-inhibition-based-on-multiple-states-of-immune-exhaustion
#19
JOURNAL ARTICLE
Irina Kareva, Jana L Gevertz
Despite the revolutionary impact of immune checkpoint inhibition on cancer therapy, the lack of response in a subset of patients, as well as the emergence of resistance, remain significant challenges. Here we explore the theoretical consequences of the existence of multiple states of immune cell exhaustion on response to checkpoint inhibition therapy. In particular, we consider the emerging understanding that T cells can exist in various states: fully functioning cytotoxic cells, reversibly exhausted cells with minimal cytotoxicity, and terminally exhausted cells...
February 9, 2024: NPJ Systems Biology and Applications
https://read.qxmd.com/read/38287079/autotransop-translating-omics-signatures-without-orthologue-requirements-using-deep-learning
#20
JOURNAL ARTICLE
Nikolaos Meimetis, Krista M Pullen, Daniel Y Zhu, Avlant Nilsson, Trong Nghia Hoang, Sara Magliacane, Douglas A Lauffenburger
The development of therapeutics and vaccines for human diseases requires a systematic understanding of human biology. Although animal and in vitro culture models can elucidate some disease mechanisms, they typically fail to adequately recapitulate human biology as evidenced by the predominant likelihood of clinical trial failure. To address this problem, we developed AutoTransOP, a neural network autoencoder framework, to map omics profiles from designated species or cellular contexts into a global latent space, from which germane information for different contexts can be identified without the typically imposed requirement of matched orthologues...
January 29, 2024: NPJ Systems Biology and Applications
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