Aoki Kiyoko F, Ueda Nobuhisa, Yamaguchi Atsuko, Kanehisa Minoru, Akutsu Tatsuya, Mamitsuka Hiroshi
Bioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto, Japan.
Bioinformatics. 2004 Aug 4;20 Suppl 1:i6-14. doi: 10.1093/bioinformatics/bth916.
The study of carbohydrate sugar chains, or glycans, has been one of slow progress mainly due to the difficulty in establishing standard methods for analyzing their structures and biosynthesis. Glycans are generally tree structures that are more complex than linear DNA or protein sequences, and evidence shows that patterns in glycans may be present that spread across siblings and into further regions that are not limited by the edges in the actual tree structure itself. Current models were not able to capture such patterns.
We have applied a new probabilistic model, called probabilistic sibling-dependent tree Markov model (PSTMM), which is able to inherently capture such complex patterns of glycans. Not only is the ability to capture such patterns important in itself, but this also implies that PSTMM is capable of performing multiple tree structure alignments efficiently. We prove through experimentation on actual glycan data that this new model is extremely useful for gaining insight into the hidden, complex patterns of glycans, which are so crucial for the development and functioning of higher level organisms. Furthermore, we also show that this model can be additionally utilized as an innovative approach to multiple tree alignment, which has not been applied to glycan chains before. This extension on the usage of PSTMM may be a major step forward for not only the structural analysis of glycans, but it may consequently prove useful for discovering clues into their function.
碳水化合物糖链(即聚糖)的研究进展一直较为缓慢,主要原因在于难以建立分析其结构和生物合成的标准方法。聚糖通常是树形结构,比线性的DNA或蛋白质序列更为复杂,并且有证据表明,聚糖中可能存在跨越兄弟姐妹甚至延伸到不受实际树形结构边界限制的更远区域的模式。当前的模型无法捕捉到此类模式。
我们应用了一种新的概率模型,称为概率性依赖兄弟姐妹的树状马尔可夫模型(PSTMM),它能够固有地捕捉聚糖的这种复杂模式。不仅捕捉此类模式的能力本身很重要,而且这还意味着PSTMM能够高效地进行多个树形结构比对。通过对实际聚糖数据进行实验,我们证明这种新模型对于深入了解聚糖隐藏的复杂模式极为有用,而这些模式对于高等生物的发育和功能至关重要。此外,我们还表明,该模型还可作为一种创新的多树比对方法,此前尚未应用于聚糖链。PSTMM在用途上的这种扩展不仅可能是聚糖结构分析的一大进步,而且最终可能有助于发现其功能线索。