A network of epigenomic and transcriptional cooperation encompassing an epigenomic master regulator in cancer

Wilson, Stephen; Filipp, Fabian V.

doi:10.1101/309484

Cited by 3 publications

(2 citation statements)

References 58 publications

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“…Epigenome-related factors act upstream in the gene network hierarchy, which is the essence of epigenomic regulation in cell fate determination [8]. When understanding epigenomic abnormalities, it is critical to consider their effects on individual genes and, at the same time, to view them as a network from a macro perspective.…”

Section: Epigenomic Regulation As a Networkmentioning

confidence: 99%

The role of epigenetics in T-cell lymphoma

Yamagishi

2022

Int J Hematol

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Malignant lymphomas are a group of diseases with epigenomic abnormalities fundamental to pathogenesis and pathophysiology. They are characterized by a high frequency of abnormalities related to DNA methylation regulators (DNMT3A, TET2, IDH2, etc.) and histone modifiers (EZH2, HDAC, KMT2D/MLL2, CREBBP, EP300, etc.). These epigenomic abnormalities directly amplify malignant clones. They also originate from a hematopoietic stem cell-derived cell lineage triggered by epigenomic changes. These characteristics are linked to their high affinity for epigenomic therapies. Hematology has led disease epigenetics in the areas of basic research, clinical research, and drug discovery. However, epigenomic regulation is generally recognized as a complex system, and gaps exist between basic and clinical research. To provide an overview of the status and importance of epigenomic abnormalities in malignant lymphoma, this review first summarizes the concept and essential importance of the epigenome, then outlines the current status and future outlook of epigenomic abnormalities in malignant lymphomas.

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Section: Epigenomic Regulation As a Networkmentioning

confidence: 99%

The role of epigenetics in T-cell lymphoma

Yamagishi

2022

Int J Hematol

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“…Epigenomics of oncogenic networks has an ability to accurately predict regulome function, epigenomic-transcriptomic cooperation, and disease progression (35). Then again, epigenetic modifications on chromatin, DNA, and RNA are complex and often context-specific, making their mechanistic understanding challenging.…”

Section: Deciphering Epigenomic Networkmentioning

confidence: 99%

Opportunities for Artificial Intelligence in Advancing Precision Medicine

Filipp

2019

Curr Genet Med Rep

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Machine learning (ML), deep learning (DL), and artificial intelligence (AI) are of increasing importance in biomedicine. The goal of this work is to show progress in ML in digital health, to exemplify future needs and trends, and to identify any essential prerequisites of AI and ML for precision health.High-throughput technologies are delivering growing volumes of biomedical data, such as largescale genome-wide sequencing assays, libraries of medical images, or drug perturbation screens of healthy, developing, and diseased tissue. Multi-omics data in biomedicine is deep and complex, offering an opportunity for data-driven insights and automated disease classification. Learning from these data will open our understanding and definition of healthy baselines and disease signatures. State-of-the-art applications of deep neural networks include digital image recognition, single cell clustering, and virtual drug screens, demonstrating breadths and power of ML in biomedicine.Significantly, AI and systems biology have embraced big data challenges and may enable novel biotechnology-derived therapies to facilitate the implementation of precision medicine approaches.

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A network of epigenomic and transcriptional cooperation encompassing an epigenomic master regulator in cancer

Wilson

Filipp

2018

npj Syst Biol Appl

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Coordinated experiments focused on transcriptional responses and chromatin states are well-equipped to capture different epigenomic and transcriptomic levels governing the circuitry of a regulatory network. We propose a workflow for the genome-wide identification of epigenomic and transcriptional cooperation to elucidate transcriptional networks in cancer. Gene promoter annotation in combination with network analysis and sequence-resolution of enriched transcriptional motifs in epigenomic data reveals transcription factor families that act synergistically with epigenomic master regulators. By investigating complementary omics levels, a close teamwork of the transcriptional and epigenomic machinery was discovered. The discovered network is tightly connected and surrounds the histone lysine demethylase KDM3A, basic helix-loop-helix factors MYC, HIF1A, and SREBF1, as well as differentiation factors AP1, MYOD1, SP1, MEIS1, ZEB1, and ELK1. In such a cooperative network, one component opens the chromatin, another one recognizes gene-specific DNA motifs, others scaffold between histones, cofactors, and the transcriptional complex. In cancer, due to the ability to team up with transcription factors, epigenetic factors concert mitogenic and metabolic gene networks, claiming the role of a cancer master regulators or epioncogenes. Significantly, specific histone modification patterns are commonly associated with open or closed chromatin states, and are linked to distinct biological outcomes by transcriptional activation or repression. Disruption of patterns of histone modifications is associated with the loss of proliferative control and cancer. There is tremendous therapeutic potential in understanding and targeting histone modification pathways. Thus, investigating cooperation of chromatin remodelers and the transcriptional machinery is not only important for elucidating fundamental mechanisms of chromatin regulation, but also necessary for the design of targeted therapeutics.

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A network of epigenomic and transcriptional cooperation encompassing an epigenomic master regulator in cancer

Cited by 3 publications

References 58 publications

The role of epigenetics in T-cell lymphoma

The role of epigenetics in T-cell lymphoma

Opportunities for Artificial Intelligence in Advancing Precision Medicine

A network of epigenomic and transcriptional cooperation encompassing an epigenomic master regulator in cancer

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