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Modeling virus-host interaction networks . Perry Evans Mahdi Sarmadi. NEF interaction sites. Roeth and Collins MMBR ‘06 . HIV-1 ELMs . Interaction prediction. Identify ELMs on HIV-1 proteins Find human proteins with functional CDs
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Modeling virus-host interaction networks Perry Evans Mahdi Sarmadi
NEF interaction sites Roeth and Collins MMBR ‘06
Interaction prediction • Identify ELMs on HIV-1 proteins • Find human proteins with functional CDs • Validate predictions using NIAID’s HIV, human interaction database of ~2K experimental interactions H1 H2
HIV-1 vs. HCV ELMs 4 interesting unique ELMs 7 interesting unique ELMs
De Novo Motif Discovery •Known motifs do not unveil the grammar of interaction between HIV-1 and human proteins •Computational motif discovery of de novo motifs is based on the virtue of Over-Representation
HIV-1 Protein Alignment Contains Invariant Regions HIV-1 TAT protein (first 65 AA of the sequence is shown)
H2 Motif Finding Results Motif Pattern HIV H1 Protein H2 Proteins H2 Matches Occ. On HIV HPRD P-Val NCBI P-Val FWY.{0,1}C..C TAT EP300 (E1A binding protein p300) 207 41 100% 1.45E-04 1.04E-05 GTF2H1 (General Transcription factor IIH) 26 5 5.25E-02 3.15E-02 TBP (TATA box binding protein) 83 15 1.76E-02 5.94E-03 TP53 (Tumor protein p53) 238 42 8.10E-04 6.61E-05 TP73 (Tumor protein p73 ) 31 8 4.19E-03 1.83E-03 CREBBP (CREB binding protein) 199 32 1.94E-02 3.69E-03 KR[KR] 96 94% 8.89E-10 1.53E-10 [IL]KQE VPR 20 50% 1.02E-07 7.46E-11
H2 Motifs: Counter Motif? E.[FIV]..[IL].K