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| 1 | Quasispecies dynamics in main core epitopes of hepatitis B virus by ultra-deep-pyrosequencing显示文摘AIM:To investigate the variability of the main immunodominant motifs of hepatitis B virus(HBV) core gene by ultra-deep-pyrosequencing(UDPS).METHODS:Four samples(2 genotype A and 2 genotype D) from 4 treatment-na ve patients were assessed for baseline variability.Two additional samples from one patient(patient 4,genotype D) were selected for analysis:one sample corresponded to a 36-mo treatment-free period from baseline and the other to the time of viral breakthrough after 18 mo of lamivudine treatment.The HBV region analyzed covered amino acids 40 to 95 of the core gene,and included the two main epitopic regions,Th50-69 and B74-84.UDPS was carried out in the Genome Sequencer FLX system(454 Life Sciences,Roche).After computer filtering of UDPS data based on a Poisson statistical model,122 813 sequences were analyzed.The most conserved position detected by UDPS was analyzed by site-directed mutagenesis and evaluated in cell culture.RESULTS:Positions with highest variability rates were mainly located in the main core epitopes,confirming their role as immune-stimulating regions.In addition,the distribution of variability showed a relationship with HBV genotype.Patient 1(genotype A) presented the lowest variability rates and patient 2(genotype A) had 3 codons with variability higher than 1%.Patient 3 and 4(both genotype D) presented 5 and 8 codons with variability higher than 1%,respectively.The median baseline frequencies showed that genotype A samples had higher variability in epitopic positions than in the other positions analyzed,approaching significance(P = 0.07,sample 1 and P = 0.05,sample 2).In contrast,there were no significant differences in variability between the epitopic and other positions in genotype D cases.Interestingly,patient 1 presented a completely mutated motif from amino acid 64 to 67(E 64 LMT 67),which is commonly recognized by T helper cells.Additionally,the variability observed in all 4 patients was particularly associated with the E 64 LMT 67 motif.Codons 78 and 79 were highly conserved in all samples,in keeping with their involvement in the interaction between the HBV virion capsid and the surface antigens(HBsAg).Of note,codon 76 was even more conserved than codons 78 and 79,suggesting a possible role in HBsAg interactions or even in hepatitis B e antigen conformation.Sequential analysis of samples from patient 4(genotype D) illustrated the dynamism of the HBV quasispecies,with strong selection of one minor baseline variant coinciding with a decrease in core variability during the treatment-free and lamivudinetreated period.The drop in variability seemed to result from a 'steady state' situation of the HBV quasispecies after selection of the variant with greatest fitness.CONCLUSION:Host immune pressure seems to be the main cause of HBV core evolution.UDPS analysis is a useful technique for studying viral quasispecies. | Maria Homs Maria Buti David Tabernero Josep Quer Alex Sanchez Noelia Corral Rafael Esteban Francisco Rodriguez-Frias | 2012 | World Journal of Gastroenterology2012，18，42： | 5 |
| 2 | Single-packet IP traceback显示文摘 | Alex C. Snoeren Craig Partridge Luis A. Sanchez Christine E. Jones Fabrice Tchakountio Beverly Schwartz Stephen T. Kent W. Timothy Strayer | 2002 | IEEE/ACM Transactions on Networking (TON)2002，，6： | 1 |
| 3 | Successes and challenges of HIV prevention in men who have sex with men显示文摘 | Patrick S Sullivan Alex Carballo-Diéguez Thomas Coates Steven M Goodreau Ian McGowan Eduard J Sanders Adrian Smith Prabuddhagopal Goswami Jorge Sanchez | 2012 | 2012 (9839)2012，，9839： | 1 |
| 4 | Detection of QTL affecting fatty acid composition in the pig显示文摘 | Alex Clop Cristina Ovilo Miguel Perez-Enciso Albert Cercos Anna Tomas Ana Fernandez Agustina Coll Josep M. Folch Carmen Barragan Isabel Diaz Maria A. Oliver Luis Varona Luis Silio Armand Sanchez Jose L. Noguera | 2003 | Mammalian Genome2003，，9： | 1 |
| 5 | Nat Methods:利用CRISPR-Cas9组合筛选发现癌症弱点显示文摘导致癌症的基因突变也会削弱癌细胞,从而使得人们有机会开发选择性地杀死它们同时不影响正常细胞的药物。这一概念被称作”合成致死性(synthetic lethality)”,这是因为这些药物仅对发生突变的(或者说合成的)细胞是致命性的。在一项新的研究中。来自美国加州大学圣地亚哥分校、加州大学旧金山分校、斯坦福大学和癌细胞图谱项目(Cancer Cell Map Initiative)的研究人员开发出一种新的方法来寻找合成致死性的基因组合。 | John Paul Shen, Ana Bojorquez-Gomez, Katherine Licon, Kristin Klepper, Daniel Pekin, Alex N Beckett, Kyle Salinas Sanchez, Jason F Kreisberg, Trey Ideker John Paul Shen, Trey Ideker, Prashant Mali John Paul Shen, Dongxin Zhao, Dan Du, Assen Roguev, Jason F Kreisberg, Nevan Krogan, Lei Qi, Trey Ideker, Prashant Mali Dongxin Zhao, Chih-Chung Kuo, Prashant Mali Roman Sasik, Amanda Birmingham, Aaron N Chang, Trey Ideker Jens Luebeck, Alex Thomas Alex Thomas, Chih-Chung Kuo, Nathan E Lewis Dan Du Assen Roguev, Nevan Krogan Nathan E Lewis Lei Qi | 2017 | 现代生物医学进展2017，17，17： | 1 |
| 6 | Single-packet IP traceback显示文摘 | Alex Snoeren Craig Partridge Luis Sanchez Christine Jones | 2005 | IEEE/ACM Transactions on Networking (TON)2005，10，6： | 1 |
| 7 | Detection of QTL affecting fatty acid composition in the pig显示文摘 | Alex Clop Cristina Ovilo Miguel Perez-Enciso Albert Cercos Anna Tomas Ana Fernandez Agustina Coll Josep M. Folch Carmen Barragan Isabel Diaz Maria A. Oliver Luis Varona Luis Silio Armand Sanchez Jose L. Noguera | 2003 | Mammalian Genome2003，，9： | 1 |
| 8 | Identification of host and viral factors involved in a dissimilar resolution of a hepatitis C virus infection显示文摘 | Maria Cubero Josep Gregori Juan I. Esteban Damir García‐Cehic Marta Bes Celia Perales Esteban Domingo Francisco Rodríguez‐Frías Silvia Sauleda Rosario Casillas Alex Sanchez Israel Ortega Rafael Esteban Jaume Guardia Josep Quer | 2014 | Liver Int2014，，6： | 1 |
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