4月26日,德国杜伊斯堡-埃森大学发表公报说,该校研究人员开发出一种能快速、准确判断I型艾滋病病毒(HIV-1)感染情况的电脑程序,这一成果将有助于提高治疗艾滋病的水平。
公报说,HIV-1侵入受体细胞是通过病毒壳膜蛋白gp120和受体细胞CD4之间的相互作用来实现的,此外还会根据不同病况而利用CCR5和CXCR4这两种辅受体细胞中的一种。通常而言,在HIV-1早期感染阶段,CCR5受感染数量较多,而CXCR4受感染则标志着HIV-1感染进入晚期。因此,能够确认被感染的辅受体细胞类型对于监测病情进展和对症下药有重要意义。
杜伊斯堡-埃森大学医学生物技术中心研究人员开发出的电脑程序能在数秒内判断出辅受体的受感染情况,其结果准确率达95%以上,可与传统检测法媲美,但速度要快得多。
这一成果发表在美国《公共科学图书馆·计算生物学》杂志上。(生物谷Bioon.com)
生物谷推荐原文出处:
PLoS Comput Biol doi:10.1371/journal.pcbi.1000743
Prediction of Co-Receptor Usage of HIV-1 from Genotype
J. Nikolaj Dybowski#, Dominik Heider#, Daniel Hoffmann*
Department of Bioinformatics, Center for Medical Biotechnology, University of Duisburg-Essen, Essen, Germany
Human Immunodeficiency Virus 1 uses for entry into host cells a receptor (CD4) and one of two co-receptors (CCR5 or CXCR4). Recently, a new class of antiretroviral drugs has entered clinical practice that specifically bind to the co-receptor CCR5, and thus inhibit virus entry. Accurate prediction of the co-receptor used by the virus in the patient is important as it allows for personalized selection of effective drugs and prognosis of disease progression. We have investigated whether it is possible to predict co-receptor usage accurately by analyzing the amino acid sequence of the main determinant of co-receptor usage, i.e., the third variable loop V3 of the gp120 protein. We developed a two-level machine learning approach that in the first level considers two different properties important for protein-protein binding derived from structural models of V3 and V3 sequences. The second level combines the two predictions of the first level. The two-level method predicts usage of CXCR4 co-receptor for new V3 sequences within seconds, with an area under the ROC curve of 0.937±0.004. Moreover, it is relatively robust against insertions and deletions, which frequently occur in V3. The approach could help clinicians to find optimal personalized treatments, and it offers new insights into the molecular basis of co-receptor usage. For instance, it quantifies the importance for co-receptor usage of a pocket that probably is responsible for binding sulfated tyrosine.