understanding communication signals during mycobacterial latency through predicted genome-wide protein interactions and boolean modeling了解通信信号在分枝杆菌延迟通过全基因组预测蛋白质相互作用和布尔建模.pdfVIP

Understanding Communication Signals during Mycobacterial Latency through Predicted Genome-Wide Protein Interactions and Boolean Modeling 1¤ 2 1,2 2 1 ¤ Shubhada R. Hegde , Hannah Rajasingh , Chandrani Das , Sharmila S. Mande , Shekhar C. Mande * 1 Structural Biology Laboratory, Centre for DNA Fingerprinting and Diagnostics, Gruhakalpa, Nampally, Hyderabad, India, 2 Bio-Sciences R D Division, TCS Innovation Labs, Tata Consultancy Services, Hyderabad, India Abstract About 90% of the people infected with Mycobacterium tuberculosis carry latent bacteria that are believed to get activated upon immune suppression. One of the fundamental challenges in the control of tuberculosis is therefore to understand molecular mechanisms involved in the onset of latency and/or reactivation. We have attempted to address this problem at the systems level by a combination of predicted functional protein:protein interactions, integration of functional interactions with large scale gene expression studies, predicted transcription regulatory network and finally simulations with a Boolean model of the network. Initially a prediction for genome-wide protein functional linkages was obtained based on genome-context methods using a Support Vector Machine. This set of protein functional linkages along with gene expression data of the available models of latency was employed to identify proteins involved in mediating switch signals during dormancy. We show that genes that are up and down regulated during dormancy are not only coordinately regulated under dormancy-like conditions but also under a variety of other experimental conditions. Thei