Department of Computer Engineering, METU, Ankara 06800, Turkey.
Department of Computer Engineering, İskenderun Technical University, Hatay 31200, Turkey.
Bioinformatics. 2020 Aug 15;36(14):4227-4230. doi: 10.1093/bioinformatics/btaa496.
iBioProVis is an interactive tool for visual analysis of the compound bioactivity space in the context of target proteins, drugs and drug candidate compounds. iBioProVis tool takes target protein identifiers and, optionally, compound SMILES as input, and uses the state-of-the-art non-linear dimensionality reduction method t-Distributed Stochastic Neighbor Embedding (t-SNE) to plot the distribution of compounds embedded in a 2D map, based on the similarity of structural properties of compounds and in the context of compounds' cognate targets. Similar compounds, which are embedded to proximate points on the 2D map, may bind the same or similar target proteins. Thus, iBioProVis can be used to easily observe the structural distribution of one or two target proteins' known ligands on the 2D compound space, and to infer new binders to the same protein, or to infer new potential target(s) for a compound of interest, based on this distribution. Principal component analysis (PCA) projection of the input compounds is also provided, Hence the user can interactively observe the same compound or a group of selected compounds which is projected by both PCA and embedded by t-SNE. iBioProVis also provides detailed information about drugs and drug candidate compounds through cross-references to widely used and well-known databases, in the form of linked table views. Two use-case studies were demonstrated, one being on angiotensin-converting enzyme 2 (ACE2) protein which is Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein receptor. ACE2 binding compounds and seven antiviral drugs were closely embedded in which two of them have been under clinical trial for Coronavirus disease 19 (COVID-19).
iBioProVis and its carefully filtered dataset are available at https://ibpv.kansil.org/ for public use.
Supplementary data are available at Bioinformatics online.
iBioProVis 是一种交互式工具，用于在目标蛋白、药物和候选药物化合物的背景下可视化分析化合物的生物活性空间。iBioProVis 工具以目标蛋白标识符（可选地还包括化合物 SMILES）作为输入，使用最先进的非线性降维方法 t 分布随机邻域嵌入（t-SNE），根据化合物结构性质的相似性和在化合物同源靶标的背景下，将嵌入在 2D 图谱中的化合物分布进行绘制。嵌入在 2D 图谱中邻近点的相似化合物可能与相同或相似的靶蛋白结合。因此，iBioProVis 可用于轻松观察一个或两个目标蛋白已知配体在 2D 化合物空间中的结构分布，并根据该分布推断同一蛋白的新结合剂，或推断对感兴趣的化合物的新潜在靶标。还提供了输入化合物的主成分分析（PCA）投影，因此用户可以交互观察通过 PCA 投影和 t-SNE 嵌入的相同化合物或一组选定的化合物。iBioProVis 还通过链接的表视图，以交叉引用广泛使用和知名数据库的形式，提供了有关药物和候选药物化合物的详细信息。展示了两个用例研究，一个是血管紧张素转换酶 2（ACE2）蛋白，它是严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）刺突蛋白的受体。ACE2 结合化合物和七种抗病毒药物紧密嵌入其中，其中两种已在临床试验中用于治疗 2019 年冠状病毒病（COVID-19）。
iBioProVis 及其经过精心筛选的数据集可在 https://ibpv.kansil.org/ 上公开使用。
补充数据可在生物信息学在线获得。
