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Full-Text Articles in Life Sciences

Cpg Site-Based Signature Predicts Survival Of Colorectal Cancer, Jiande Wu, Lu Zhang, Aditi Kuchi, David Otohinoyi, Chindo Hicks Dec 2022

Cpg Site-Based Signature Predicts Survival Of Colorectal Cancer, Jiande Wu, Lu Zhang, Aditi Kuchi, David Otohinoyi, Chindo Hicks

School of Medicine Faculty Publications

Background: A critical unmet medical need in clinical management of colorectal cancer (CRC) pivots around lack of noninvasive and or minimally invasive techniques for early diagnosis and prognostic prediction of clinical outcomes. Because DNA methylation can capture the regulatory landscape of tumors and can be measured in body fluids, it provides unparalleled opportunities for the discovery of early diagnostic and prognostics markers predictive of clinical outcomes. Here we investigated use of DNA methylation for the discovery of potential clinically actionable diagnostic and prognostic markers for predicting survival in CRC. Methods: We analyzed DNA methylation patterns between tumor and control samples …


Continuous Fluorescence-Based Endonuclease-Coupled Dna Methylation Assay To Screen For Dna Methyltransferase Inhibitors, Rebecca Switzer, Katie A. Ward, Jessica Medrano Aug 2022

Continuous Fluorescence-Based Endonuclease-Coupled Dna Methylation Assay To Screen For Dna Methyltransferase Inhibitors, Rebecca Switzer, Katie A. Ward, Jessica Medrano

Faculty Journal Articles

DNA methylation, a form of epigenetic gene regulation, is important for normal cellular function. In cells, proteins called DNA methyltransferases (DNMTs) establish and maintain the DNA methylation pattern. Changes to the normal DNA methylation pattern are linked to cancer development and progression, making DNMTs potential cancer drug targets. Thus, identifying and characterizing novel small molecule inhibitors of these enzymes is of great importance. This paper presents a protocol that can be used to screen for DNA methyltransferase inhibitors. The continuous coupled kinetics assay allows for initial velocities of DNA methylation to be determined in the presence and absence of potential …


Luteolin Causes 5′Cpg Demethylation Of The Promoters Of Tsgs And Modulates The Aberrant Histone Modifications, Restoring The Expression Of Tsgs In Human Cancer Cells, Sreepoorna Pramodh, Ritu Raina, Arif Hussain, Sali Abubaker Bagabir, Shafiul Haque, Syed Tasleem Raza, Mohammad Rehan Ajamal, Shalini Behl, Deepika Bhagavatula Apr 2022

Luteolin Causes 5′Cpg Demethylation Of The Promoters Of Tsgs And Modulates The Aberrant Histone Modifications, Restoring The Expression Of Tsgs In Human Cancer Cells, Sreepoorna Pramodh, Ritu Raina, Arif Hussain, Sali Abubaker Bagabir, Shafiul Haque, Syed Tasleem Raza, Mohammad Rehan Ajamal, Shalini Behl, Deepika Bhagavatula

All Works

Cancer progression is linked to abnormal epigenetic alterations such as DNA methylation and histone modifications. Since epigenetic alterations, unlike genetic changes, are heritable and reversible, they have been considered as interesting targets for cancer prevention and therapy by dietary compounds such as luteolin. In this study, epigenetic modulatory behaviour of luteolin was analysed on HeLa cells. Various assays including colony forming and migration assays, followed by biochemical assays of epigenetic enzymes including DNA methyltransferase, histone methyl transferase, histone acetyl transferase, and histone deacetylases assays were performed. Furthermore, global DNA methylation and methylation‐specific PCR for examining the methylation status of CpG …


Completing Single-Cell Dna Methylome Profiles Via Transfer Learning Together With Kl-Divergence, Sanjeeva Dodlapati, Zongliang Jiang, Jiangwen Sun Jan 2022

Completing Single-Cell Dna Methylome Profiles Via Transfer Learning Together With Kl-Divergence, Sanjeeva Dodlapati, Zongliang Jiang, Jiangwen Sun

Computer Science Faculty Publications

The high level of sparsity in methylome profiles obtained using whole-genome bisulfite sequencing in the case of low biological material amount limits its value in the study of systems in which large samples are difficult to assemble, such as mammalian preimplantation embryonic development. The recently developed computational methods for addressing the sparsity by imputing missing have their limits when the required minimum data coverage or profiles of the same tissue in other modalities are not available. In this study, we explored the use of transfer learning together with Kullback-Leibler (KL) divergence to train predictive models for completing methylome profiles with …


For Whom The Bell Tolls: Psychopathological And Neurobiological Correlates Of The Dna Methylation Index Of Time-To-Death, Sage E. Hawn, Xiang Zhao, Danielle R. Sullivan, Mark Logue, Dana Fein-Schaffer, William Milberg, Regina Mcglinchey, Mark W. Miller, Erika J. Wolf Jan 2022

For Whom The Bell Tolls: Psychopathological And Neurobiological Correlates Of The Dna Methylation Index Of Time-To-Death, Sage E. Hawn, Xiang Zhao, Danielle R. Sullivan, Mark Logue, Dana Fein-Schaffer, William Milberg, Regina Mcglinchey, Mark W. Miller, Erika J. Wolf

Psychology Faculty Publications

Psychopathology is a risk factor for accelerated biological aging and early mortality. We examined associations between broad underlying dimensions of psychopathology (reflecting internalizing and externalizing psychiatric symptoms), PTSD, and age-adjusted GrimAge (“GrimAge residuals”), a DNA methylation biomarker of mortality risk relative to age. We also examined neurobiological correlates of GrimAge residuals, including neurocognitive functioning, blood-based biomarkers (of inflammation, neuropathology, metabolic disease), and cortical thickness. Data from two independent trauma-exposed military cohorts (n = 647 [62.9% male, Mage = 52], n = 434 [90% male, Mage = 32]) were evaluated using linear regression models to test associations between …