![]() ; ; et al in Bioinformatics (2012), 28(19), 2556-9 ISCB, the International Society for Computational Biology, organizes the largest event in the field of computational biology and bioinformatics, namely the annual ISMB, the international conference on ... [more ▼] ISCB, the International Society for Computational Biology, organizes the largest event in the field of computational biology and bioinformatics, namely the annual ISMB, the international conference on Intelligent Systems for Molecular Biology. This year at ISMB 2012 in Long Beach, ISCB celebrated the 20th anniversary of its flagship meeting. ISCB is a young, lean and efficient society that aspires to make a significant impact with only limited resources. Many constraints make the choice of venues for ISMB a tough challenge. Here, we describe those challenges and invite the contribution of ideas for solutions. [less ▲] Detailed reference viewed: 145 (1 UL)![]() ![]() ; ; et al in AIDS Research and Human Retroviruses (2010), 26(3), 275-278 In HIV-1, thymidine analogue mutations (TAMs) cluster in one of two groups (215Y, 41L, 210W, or 215F, 219E/Q), representing two independent mutational patterns (T215Y and T215F cluster, respectively). The ... [more ▼] In HIV-1, thymidine analogue mutations (TAMs) cluster in one of two groups (215Y, 41L, 210W, or 215F, 219E/Q), representing two independent mutational patterns (T215Y and T215F cluster, respectively). The mechanisms by which these pathways are selected are not fully understood. To investigate possible factors driving the selection of the TAMs, we analyzed the TAM patterns with regard to the respective treatment, viral load, and HLA in 18 children all infected from a common source of HIV-1 clade G virus and initially treated with zidovudine. The HIV reverse transcriptase sequences of 14/18 children carried at least one TAM. At first sampling date, the T215Y-linked pattern was observed in five cases and the T215F cluster was seen in nine. During the follow-up period, three patients changed their patterns. Children treated with identical NRTI combinations at the first sampling date developed different pathways. Under AZT/d4T therapies, an association was found between the HLA B*13 (in combination with HLA DRB1*0701) and the mutation T215Y. The mutation T215Y reverted in three out of four patients who discontinued AZT/d4T treatment. We speculate that in the context of these subtype G viruses, the development of the T215Y mutation may be strongly disfavored whereas the presence of HLA B*13 may counteract this effect and permit its development. [less ▲] Detailed reference viewed: 92 (0 UL)![]() ; Roomp, Kirsten ![]() in Clinical and Vaccine Immunology (2007), 14(10), 1266-1273 The objective of this study was a comprehensive analysis of the immune-driven evolution of viruses of human immunodeficiency virus type 1 (HIV-1) clade B in a large patient cohort treated at a single ... [more ▼] The objective of this study was a comprehensive analysis of the immune-driven evolution of viruses of human immunodeficiency virus type 1 (HIV-1) clade B in a large patient cohort treated at a single hospital in Germany and its implications for antiretroviral therapy. We examined the association of the HLA-A, HLA-B, and HLA-DRB1 alleles with the emergence of mutations in the complete protease gene and the first 330 codons of the reverse transcriptase (RT) gene of HIV-1, studying their distribution and persistence and their impact on antiviral drug therapy. The clinical data for 179 HIV-infected patients, the results of HLA genotyping, and virus sequences were analyzed using a variety of statistical approaches. We describe new HLA-associated mutations in both viral protease and RT, several of which are associated with HLA-DRB1. The mutations reported are remarkably persistent within our cohort, developing more slowly in a minority of patients. Interestingly, several HLA-associated mutations occur at the same positions as drug resistance mutations in patient viruses, where the viral sequence was acquired before exposure to these drugs. The influence of HLA on thymidine analogue mutation pathways was not observed. We were able to confirm immune-driven selection pressure by major histocompatibility complex (MHC) class I and II alleles through the identification of HLA-associated mutations. HLA-B alleles were involved in more associations (68%) than either HLA-A (23%) or HLA-DRB1 (9%). As several of the HLA-associated mutations lie at positions associated with drug resistance, our results indicate possible negative effects of HLA genotypes on the development of HIV-1 drug resistance. [less ▲] Detailed reference viewed: 98 (0 UL)![]() ; ; et al in Bioinformatics (2005), 21(21), 3943-50 Summary: The development of drug resistance is a major obstacle to successful treatment of HIV infection. The extraordinary replication dynamics of HIV facilitates its escape from selective pressure ... [more ▼] Summary: The development of drug resistance is a major obstacle to successful treatment of HIV infection. The extraordinary replication dynamics of HIV facilitates its escape from selective pressure exerted by the human immune system and by combination drug therapy. We have developed several computational methods whose combined use can support the design of optimal antiretroviral therapies based on viral genomic data. [less ▲] Detailed reference viewed: 98 (0 UL) |
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