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• W3025341310 abstract "Recent advances in omics technologies have empowered multitissue multiomics systems biology, a discipline that aims to dissect the multidimensional complexities of human diseases. Studies integrating large-scale genetic associations with other omics have resolved tissue-specific molecular networks and pathways perturbed by genetic risks of diseases. Systematic investigation of multiomic domains across tissues in response to environmental exposure, such as diet, chemicals, and pathogens, has revealed fresh insights into the target tissues, genes, and molecular networks underlying environmental risks of diseases. The holistic within- and between-tissue networks of diseases, unraveled by systems biology, offer comprehensive mechanistic insights and help formulate data-driven hypotheses to guide network-based medicine targeting specific tissues, genes, and pathways tailored to specific risks. Most complex diseases involve genetic and environmental risk factors, engage multiple cells and tissues, and follow a polygenic or omnigenic model depicting numerous genes contributing to pathophysiology. These multidimensional complexities pose challenges to traditional approaches that examine individual factors. In turn, multitissue multiomics systems biology has emerged to comprehensively elucidate within- and cross-tissue molecular networks underlying gene-by-environment interactions and contributing to complex diseases. The power of systems biology in retrieving novel insights and formulating new hypotheses has been well documented. However, the field faces various challenges that call for debate and action. In this opinion article, I discuss the concepts, benefits, current state, and challenges of the field and point to the next steps toward network-based systems medicine. Most complex diseases involve genetic and environmental risk factors, engage multiple cells and tissues, and follow a polygenic or omnigenic model depicting numerous genes contributing to pathophysiology. These multidimensional complexities pose challenges to traditional approaches that examine individual factors. In turn, multitissue multiomics systems biology has emerged to comprehensively elucidate within- and cross-tissue molecular networks underlying gene-by-environment interactions and contributing to complex diseases. The power of systems biology in retrieving novel insights and formulating new hypotheses has been well documented. However, the field faces various challenges that call for debate and action. In this opinion article, I discuss the concepts, benefits, current state, and challenges of the field and point to the next steps toward network-based systems medicine. genetic loci that are associated with the expression levels of a gene transcript. eQTLs are identified by examining the correlation between the genotype at each genetic locus with the copy numbers of an expressed transcript. eQTLs are usually tissue specific because gene expression is regulated in a tissue-specific manner. a popular and common type of genetic study in human populations to identify genetic variants that are associated with increased or decreased risk of a disease. comprised of nodes, which are indicative of the molecular entities, such as genes, proteins, or metabolites, and edges that illustrate the connections or links between nodes. Edges can be regulatory relations, correlations, physical interactions, or enzymatic and biochemical reactions (Figure 2). concerted analyses of various ‘omics’ or all biological entities participating in the functions of a cell, tissue, or organism. Examples of omics domains include the genome (the DNA sequence and its variations across individuals), epigenome (chemical modifications and structural conformations of the DNA sequence; noncoding RNA molecules), transcriptome (the expressed mRNA transcripts from a genome), proteome (all proteins translated from gene transcripts as well as various chemical modifications of proteins), metabolome (complete set of small molecules and chemicals), and microbiome (microbial species inhabiting the human body along with their genome information). a research discipline that utilizes modern high-throughput multiomic technologies to examine diverse types of biomolecules in multiple tissues simultaneously to generate comprehensive global views of molecular interactions within and between tissues. the model hypothesizes that all genes likely play a role in disease development because of their interconnections with other genes. The further away a gene is from an important disease gene, the weaker effect it likely has on a disease. However, even weak genes can accumulate disease risks over the life span. the model states that more than one gene contributes to disease development. the type of research that investigates the effect of individual biological factors, such as genes or proteins, one at a time. Typically, it involves activating or inhibiting the molecule to observe downstream molecular or functional changes." @default.
• W3025341310 created "2020-05-21" @default.
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• W3025341310 date "2020-08-01" @default.
• W3025341310 modified "2023-10-17" @default.
• W3025341310 title "Multitissue Multiomics Systems Biology to Dissect Complex Diseases" @default.
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• W3025341310 doi "https://doi.org/10.1016/j.molmed.2020.04.006" @default.
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