Beyond whole-genome or whole-exome sequencing, the understanding of functional principles is considered essential to achieve clinical success. Now the concept of molecular networks orchestrating gene expression and cell control is explored by the rapidly evolving field of network biology. Breakthrough genome-wide mapping technologies provide now abundance evidence for regulatory networks. These techniques are: |
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• ChIP-seq, and • 5C ( chromosome conformation capture carbon copy ). The use of ChIP-seq after RNA-seq-based identification of transcription factors can reveal the DNA binding events and transcriptional regulatory networks. Application of 5C has showed that promoters and distal elements in chromosomes are engaged in multiple long-range interactions to form complex networks. The data start to place genes and regulatory elements in three-dimensional context, revealing their functional relationships. The ~ 80% of the human genome is full of functional elements and disease-causing regulatory variants [1,2]. hese advances in genomic network biology and the ambitious goal to correlated interactions network landscape with clinical data to predict disease phenotypes such as prognosis and therapeutic response or resistance to drugs shape the future network medicine [3-6].
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References
1. Roukos DH. Networks medicine: From reductionism to evidence of complex dynamic biomolecular interactions. Pharmacogenomics. 12(5): 695-698 (2011).
2. Gerstein MB, Kundaje A, Hariharan M, et al . Architecture of the human regulatory network derived from ENCODE data. Nature. 489(7414):91-100 (2012).
3. Sanyal A, Lajoie BR, Jain G, Dekker J. The long-range interaction landscape of gene promoters. Nature. 489(7414):109-113. doi: 10.1038/nature11279 (2012).
4. Barabási AL, Gulbahce N, Loscalzo J. Network medicine: A network-based approach to human disease. Nat Rev Genet. 12, 56-68 (2011).
5. Roukos DH. Disrupting cancer cells biocircuits with interactome-based drugs: Is “clinical” innovation realistic? Expert Rev Proteomics 9(4), 349-353 (2012).
6. Camacho DF, Pienta KJ. Disrupting the networks of cancer. Clin Cancer Res 18(10), 2801-2808 (2012). |
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