Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts, 02115, USA.
AIDS Res Ther. 2010 Dec 14;7:43. doi: 10.1186/1742-6405-7-43.
The population of HIV replicating within a host consists of independently evolving and interacting sub-populations that can be genetically distinct within anatomical compartments. HIV replicating within the brain causes neurocognitive disorders in up to 20-30% of infected individuals and is a viral sanctuary site for the development of drug resistance. The primary determinant of HIV neurotropism is macrophage tropism, which is primarily determined by the viral envelope (env) gene. However, studies of genetic aspects of HIV replicating in the brain are hindered because existing repositories of HIV sequences are not focused on neurotropic virus nor annotated with neurocognitive and neuropathological status. To address this need, we constructed the HIV Brain Sequence Database.
The HIV Brain Sequence Database is a public database of HIV envelope sequences, directly sequenced from brain and other tissues from the same patients. Sequences are annotated with clinical data including viral load, CD4 count, antiretroviral status, neurocognitive impairment, and neuropathological diagnosis, all curated from the original publication. Tissue source is coded using an anatomical ontology, the Foundational Model of Anatomy, to capture the maximum level of detail available, while maintaining ontological relationships between tissues and their subparts. 44 tissue types are represented within the database, grouped into 4 categories: (i) brain, brainstem, and spinal cord; (ii) meninges, choroid plexus, and CSF; (iii) blood and lymphoid; and (iv) other (bone marrow, colon, lung, liver, etc). Patient coding is correlated across studies, allowing sequences from the same patient to be grouped to increase statistical power. Using Cytoscape, we visualized relationships between studies, patients and sequences, illustrating interconnections between studies and the varying depth of sequencing, patient number, and tissue representation across studies. Currently, the database contains 2517 envelope sequences from 90 patients, obtained from 22 published studies. 1272 sequences are from brain; the remaining 1245 are from blood, lymph node, spleen, bone marrow, colon, lung and other non-brain tissues. The database interface utilizes a faceted interface, allowing real-time combination of multiple search parameters to assemble a meta-dataset, which can be downloaded for further analysis.
This online resource, which is publicly available at http://www.HIVBrainSeqDB.org, will greatly facilitate analysis of the genetic aspects of HIV macrophage tropism, HIV compartmentalization and evolution within the brain and other tissue reservoirs, and the relationship of these findings to HIV-associated neurological disorders and other clinical consequences of HIV infection.
宿主中复制 HIV 的人群由独立进化和相互作用的亚群组成，这些亚群在解剖隔室中可能具有遗传上的差异。HIV 在大脑中的复制会导致高达 20-30%的感染者出现神经认知障碍，并且是产生耐药性的病毒避难所。HIV 嗜神经性的主要决定因素是巨噬细胞嗜性，主要由病毒包膜（env）基因决定。然而，由于现有的 HIV 序列存储库并非专注于嗜神经性病毒，也没有对神经认知和神经病理学状态进行注释，因此对 HIV 在大脑中复制的遗传方面的研究受到阻碍。为了解决这一需求，我们构建了 HIV 大脑序列数据库。
HIV 大脑序列数据库是一个公共的 HIV 包膜序列数据库，这些序列是直接从大脑和同一患者的其他组织中测序得到的。序列与包括病毒载量、CD4 计数、抗逆转录病毒状态、神经认知障碍和神经病理学诊断在内的临床数据进行了注释，所有这些数据都是从原始出版物中整理出来的。组织来源使用解剖学本体，即基础解剖学模型进行编码，以获取可用的最大详细信息，同时保持组织与其子部分之间的本体关系。数据库中包含 44 种组织类型，分为四类：（i）大脑、脑干和脊髓；（ii）脑膜、脉络丛和脑脊液；（iii）血液和淋巴；以及（iv）其他（骨髓、结肠、肺、肝等）。患者编码在研究之间相互关联，允许将来自同一患者的序列分组，以增加统计效力。使用 Cytoscape，我们可视化了研究、患者和序列之间的关系，说明了研究之间的相互联系以及不同研究中测序深度、患者数量和组织代表性的差异。目前，该数据库包含来自 90 名患者的 2517 个包膜序列，来自 22 个已发表的研究。1272 个序列来自大脑；其余 1245 个序列来自血液、淋巴结、脾脏、骨髓、结肠、肺和其他非脑组织。数据库界面利用分面接口，允许实时组合多个搜索参数以组装元数据集，该数据集可下载进行进一步分析。
该在线资源可公开获取，网址为 http://www.HIVBrainSeqDB.org，将极大地促进 HIV 巨噬细胞嗜性、HIV 分隔和在大脑和其他组织储库中进化的遗传方面的分析，以及这些发现与 HIV 相关的神经障碍和 HIV 感染的其他临床后果之间的关系。
