Stochastic models are key to understanding the intricate dynamics of gene expression. However, the simplest models that only account for active and inactive states of a gene fail to capture common observations in both prokaryotic and eukaryotic organisms. Here, we consider multistate models of gene expression that generalize the canonical Telegraph process and are capable of capturing the joint effects of transcription factors, heterochromatin state, and DNA accessibility (or, in prokaryotes, sigma-factor activity) on transcript abundance. We propose two approaches for solving classes of these generalized systems. The first approach offers a fresh perspective on a general class of multistate models and allows us to "decompose" more complicated systems into simpler processes, each of which can be solved analytically. This enables us to obtain a solution of any model from this class. Next, we develop an approximation method based on a power series expansion of the stationary distribution for an even broader class of multistate models of gene transcription. We further show that models from both classes cannot have a heavy-tailed distribution in the absence of extrinsic noise. The combination of analytical and computational solutions for these realistic gene expression models also holds the potential to design synthetic systems and control the behavior of naturally evolved gene expression systems in guiding cell-fate decisions.
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Sci Rep
December 2024
Department of Biology, University of South Dakota, 414 East Clark Street, Vermillion, SD, 57069-2390, USA.
Psychological distress, including anxiety or mood disorders, emanates from the onset of chronic/unpredictable stressful events. Symptoms in the form of maladaptive behaviors are learned and difficult to treat. While the origin of stress-induced disorders seems to be where learning and stress intersect, this relationship and molecular pathways involved remain largely unresolved.
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December 2024
Department of Orthopedics, The Second Affiliated hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi Province, China.
The DNA cross-link repair 1B (DCLRE1B) gene is involved in repairing cross-links between DNA strands, including those associated with Hoyeraal-Hreidarsson syndrome and congenital dyskeratosis. However, its role in tumours is not well understood. DCLRE1B expression profiles were examined in tumour tissues and normal tissues using TCGA, GTEx, and TARGET datasets.
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December 2024
Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, 410078, Hunan, P. R. China.
Dopamine (DA) plays important roles in various behaviors, including learning and motivation. Recently, THOC5 was identified as an important regulator in the development of dopaminergic neurons. However, how THOC5 is regulated has not been explored.
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December 2024
School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People's Republic of China.
Cuproptosis, a newly identified form of cell death, has drawn increasing attention for its association with various cancers, though its specific role in colorectal cancer (CRC) remains unclear. In this study, transcriptomic and clinical data from CRC patients available in the TCGA database were analyzed to investigate the impact of cuproptosis. Differentially expressed genes linked to cuproptosis were identified using Weighted Gene Co-Expression Network Analysis (WGCNA).
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December 2024
Laboratory of Cellular Biophysics, The Rockefeller University, New York, NY, USA.
Fibrolamellar Hepatocellular Carcinoma (FLC) is a rare liver cancer characterized by a fusion oncokinase of the genes DNAJB1 and PRKACA, the catalytic subunit of protein kinase A (PKA). A few FLC-like tumors have been reported showing other alterations involving PKA. To better understand FLC pathogenesis and the relationships among FLC, FLC-like, and other liver tumors, we performed a massive multi-omics analysis.
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