Background And Objective: Recently, differential DNA Methylation is known to affect the regulatory mechanism of biological pathways. A pathway encompasses a set of interacting genes or gene products that altogether perform a given biological function. Pathways often encode strong methylation signatures that are capable of distinguishing biologically distinct subtypes. Even though Next Generation Sequencing techniques such as MeDIP-seq and MBD-isolated genome sequencing (MiGS) allow for genome-wide identification of clinical and biological subtypes, there is a pressing need for computational methods to compare epigenetic signatures across pathways.
Methods: A novel alignment method, called DEEPAligner (Deep Encoded Epigenetic Pathway Aligner), is proposed in this paper that finds functionally consistent and topologically sound alignments of epigenetic signatures from pathway networks. A deep embedding framework is used to obtain epigenetic signatures from pathways which are then aligned for functional consistency and local topological similarity.
Results: Experiments on four benchmark cancer datasets reveal epigenetic signatures that are conserved in cancer-specific and across-cancer subtypes.
Conclusion: The proposed deep embedding framework obtains highly coherent signatures that are aligned for biological as well as structural orthology. Comparison with state-of-the-art network alignment methods clearly suggest that the proposed method obtains topologically and functionally more consistent alignments.
Availability: http://bdbl.nitc.ac.in/DEEPAligner.
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http://dx.doi.org/10.1016/j.compbiolchem.2018.01.002 | DOI Listing |
Phys Chem Chem Phys
January 2025
Université Paris Cité, CNRS, Laboratoire de Biochimie Théorique, 13 rue Pierre et Marie Curie, 75005, Paris, France.
Tetramethylammonium (TMA) is a ubiquitous cationic motif in biochemistry, found in the charged choline headgroup of membrane phospholipids and in tri-methylated lysine residues, which modulates histone-DNA interactions and impacts epigenetic mechanisms. TMA interactions with anionic species, particularly carboxylate groups of amino acid residues and extracellular sugars, are of substantial biological relevance, as these interactions mediate a wide range of cellular processes. This study investigates the molecular interactions between TMA and acetate, representing carboxylate-containing groups, using neutron scattering experiments complemented by force fields and molecular dynamics (MD) simulations.
View Article and Find Full Text PDFCardiovasc Diabetol
January 2025
Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010, Málaga, Spain.
Background: The prevalence of obesity and type 2 diabetes mellitus (T2DM) is rising globally, particularly among children exposed to adverse intrauterine environments, such as those associated with gestational diabetes mellitus (GDM). Epigenetic modifications, specifically DNA methylation, have emerged as mechanisms by which early environmental exposures can predispose offspring to metabolic diseases. This study aimed to investigate DNA methylation differences in children born to mothers with GDM compared to non-GDM mothers, using saliva samples, and to assess the association of these epigenetic patterns with early growth measurements.
View Article and Find Full Text PDFMol Neurobiol
January 2025
Translational Oncology Laboratory, Department of Zoology, Hansraj College, Delhi University, New Delhi, 110007, India.
This review explores the current understanding and recent advancements in neuroblastoma, one of the most common extracranial solid pediatric cancers, accounting for ~ 15% of childhood cancer-related mortality. The hallmarks of NBL, including angiogenesis, metastasis, apoptosis resistance, cell cycle dysregulation, drug resistance, and responses to hypoxia and ROS, underscore its complex biology. The tumor microenvironment's significance in disease progression is acknowledged in this study, along with the pivotal role of cancer stem cells in sustaining tumor growth and heterogeneity.
View Article and Find Full Text PDFWhile inputs regulating CD4 T helper cell (Th) differentiation are well-defined, the integration of downstream signaling with transcriptional and epigenetic programs that define Th-lineage identity remain unresolved. PI3K signaling is a critical regulator of T cell function; activating mutations affecting PI3Kδ result in an immunodeficiency with multiple T cell defects. Using mice expressing activated-PI3Kδ, we found aberrant expression of proinflammatory Th1-signature genes under Th2-inducing conditions, both and .
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Computational Biology and Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Macrophages undergo polarization, resulting in distinct phenotypes. These transitions, including de-/repolarization, lead to hysteresis, where cells retain genetic and epigenetic signatures of previous states, influencing macrophage function. We previously identified a set of interferon-stimulated genes (ISGs) associated with high lipid levels in macrophages that exhibited hysteresis following M1 polarization, suggesting potential alterations in lipid metabolism.
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