Automated Motif Discovery from Glycan Array Data
Automated Motif Discovery from Glycan Array Data
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DOI：
10.1089/omi.2012.0013
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发表时间：
2012-10-01
影响因子：
3.3
通讯作者：
Smith, David F.
中科院分区：
文献类型：
--
作者：
Cholleti, Sharath R.;Agravat, Sanjay;Smith, David F.
在微阵列上评估聚糖结合蛋白（GBP）或凝集素与聚糖的相互作用会产生大型数据集，这使得难以鉴定与GBP的最高表观结合强度相关的聚糖结构基序或决定簇。我们已经开发了一种计算方法，称为GlycanMotifMiner，它使用GBP与聚糖微阵列内聚糖的相对结合来自动揭示GBP识别的聚糖结构基序。我们实现了一个基于Web的图形界面的软件，用户探索和可视化发现的图案。使用五种植物凝集素SNA、HPA、PNA、Con A和UEA-I测定GlycanMotifMiner的效用。对来自不同蛋白浓度下凝集素分析的数据进行处理，以基于其相对结合强度对聚糖进行排序。基序定义为存在于大量结合聚糖和少量非结合聚糖中的聚糖子结构，然后通过我们的算法发现并显示在基于网络的图形用户界面（http：//www.example.com）中。glycanmotifminer.emory.edu该信息用于定义GBP的聚糖结合特异性。将结果与通过手动方法产生的这些凝集素的已知聚糖特异性进行比较。还使用从重组形式的人半乳糖凝集素-8获得的聚糖微阵列数据进行了更复杂的分析。所有这些凝集素的结果表明，GlycanMotifMiner鉴定了文献中已知的主要基序，沿着一些意想不到的新结合基序。
Assessing interactions of a glycan-binding protein (GBP) or lectin with glycans on a microarray generates large datasets, making it difficult to identify a glycan structural motif or determinant associated with the highest apparent binding strength of the GBP. We have developed a computational method, termed GlycanMotifMiner, that uses the relative binding of a GBP with glycans within a glycan microarray to automatically reveal the glycan structural motifs recognized by a GBP. We implemented the software with a web-based graphical interface for users to explore and visualize the discovered motifs. The utility of GlycanMotifMiner was determined using five plant lectins, SNA, HPA, PNA, Con A, and UEA-I. Data from the analyses of the lectins at different protein concentrations were processed to rank the glycans based on their relative binding strengths. The motifs, defined as glycan substructures that exist in a large number of the bound glycans and few non-bound glycans, were then discovered by our algorithm and displayed in a web-based graphical user interface (http://glycanmotifminer.emory.edu). The information is used in defining the glycan-binding specificity of GBPs. The results were compared to the known glycan specificities of these lectins generated by manual methods. A more complex analysis was also carried out using glycan microarray data obtained for a recombinant form of human galectin-8. Results for all of these lectins show that GlycanMotifMiner identified the major motifs known in the literature along with some unexpected novel binding motifs.