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Multi-omics profiling: the way towards precision medicine in metabolic diseases.

ABSTRACT: Metabolic diseases including type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and metabolic syndrome (MetS) are alarming health burdens around the world, while therapies for these diseases are far from satisfying as their etiologies are not completely clear yet. T2DM, NAFLD, and MetS are all complex and multifactorial metabolic disorders based on the interactions between genetics and environment. Omics studies such as genetics, transcriptomics, epigenetics, proteomics, and metabolomics are all promising approaches in accurately characterizing these diseases. And the most effective treatments for individuals can be achieved via omics pathways, which is the theme of precision medicine. In this review, we summarized the multi-omics studies of T2DM, NAFLD, and MetS in recent years, provided a theoretical basis for their pathogenesis and the effective prevention and treatment, and highlighted the biomarkers and future strategies for precision medicine.

SUBMITTER: Hu C

PROVIDER: S-EPMC8697344 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Multi-omics profiling: the way towards precision medicine in metabolic diseases.

Hu Cheng C Jia Weiping W

Journal of molecular cell biology 20210818

Metabolic diseases including type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and metabolic syndrome (MetS) are alarming health burdens around the world, while therapies for these diseases are far from satisfying as their etiologies are not completely clear yet. T2DM, NAFLD, and MetS are all complex and multifactorial metabolic disorders based on the interactions between genetics and environment. Omics studies such as genetics, transcriptomics, epigenetics, proteomics, ...[more]

PMID: 34406397

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Project description:Acute myeloid leukemia (AML), as the most common malignancy of the hematopoietic system, poses challenges in treatment efficacy, relapse, and drug resistance. In this study, we have utilized 151 RNA sequencing datasets, 194 DNA methylation datasets, and 200 somatic mutation datasets from the AML cohort in the TCGA database to develop a multi-omics stratification model. This model enables comparison of prognosis, clinical features, gene mutations, immune microenvironment and drug sensitivity across subgroups. External validation datasets have been sourced from the GEO database, which includes 562 mRNA datasets and 136 miRNA datasets from 984 adult AML patients. Through multi-omics-based stratification model, we classified 126 AML patients into 4 clusters (CS). CS4 had the best prognosis, with the youngest age, highest M3 subtype proportion, fewest copy number alterations, and common mutations in WT1, FLT3, and KIT genes. It showed sensitivity to HDAC inhibitors and BCL-2 inhibitors. Both the M3 subtype and CS4 were identified as independent protective factors for survival. Conversely, CS3 had the worst prognosis due to older age, high copy number alterations, and frequent mutations in RUNX1, DNMT3A, and TP53 genes. Additionally, it showed higher proportions of cytotoxic cells and Tregs, suggesting potential sensitivity to mTOR inhibitors. CS1 had a better prognosis than CS2, with more copy number alterations, while CS2 had higher monocyte proportions. CS1 showed good sensitivity to cytarabine, while CS2 was sensitive to RXR agonists. Both CS1 and CS2, which predominantly featured mutations in FLT3, NPM1, and DNMT3A genes, benefited from FLT3 inhibitors. Using the Kappa test, our stratification model underwent robust validation in the miRNA and mRNA external validation datasets. With advancements in sequencing technology and machine learning algorithms, AML is poised to transition towards multi-omics precision medicine in the future. We aspire for our study to offer new perspectives on multi-drug combination clinical trials and multi-targeted precision medicine for AML.

Dataset Information

Multi-omics profiling: the way towards precision medicine in metabolic diseases.

Publications

Multi-omics profiling: the way towards precision medicine in metabolic diseases.

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