決定グラフ構造によるネットワーク解析の研究

京都大学新制・課程博士博士(情報学)甲第25443号情博第881号京都大学大学院情報学研究科通信情報システム専攻(主査)教授 湊 真一, 教授 大木 英司, 教授 山本 章博学位規則第4条第1項該当Doctor of InformaticsKyoto UniversityDFA

Fully Dynamic Connectivity Oracles under General Vertex Updates

We study the following dynamic graph problem: given an undirected graph G, we maintain a connectivity oracle between any two vertices in G under any on-line sequence of vertex deletions and insertions with incident edges. We propose two algorithms for this problem: an amortized update time deterministic one and a worst case update time Monte Carlo one. Both of them allow an arbitrary number of new vertices to insert. The update time complexity of the former algorithm is no worse than the existing algorithms, which allow only limited number of vertices to insert. Moreover, for relatively dense graphs, we can expect that the update time bound of the former algorithm meets a lower bound, and that of the latter algorithm can be seen as a substantial improvement of the existing result by introducing randomization

Discrimination between biological interfaces and crystal-packing contacts

A discrimination method between biologically relevant interfaces and artificial crystal-packing contacts in crystal structures was constructed. The method evaluates protein-protein interfaces in terms of complementarities for hydrophobicity, electrostatic potential and shape on the protein surfaces, and chooses the most probable biological interfaces among all possible contacts in the crystal. The method uses a discriminator named as “COMP”, which is a linear combination of the complementarities for the above three surface features and does not correlate with the contact area. The discrimination of homo-dimer interfaces from symmetry-related crystal-packing contacts based on the COMP value achieved the modest success rate. Subsequent detailed review of the discrimination results raised the success rate to about 88.8%. In addition, our discrimination method yielded some clues for understanding the interaction patterns in several examples in the PDB. Thus, the COMP discriminator can also be used as an indicator of the “biological-ness” of protein-protein interfaces

eF-seek: prediction of the functional sites of proteins by searching for similar electrostatic potential and molecular surface shape

We have developed a method to predict ligand-binding sites in a new protein structure by searching for similar binding sites in the Protein Data Bank (PDB). The similarities are measured according to the shapes of the molecular surfaces and their electrostatic potentials. A new web server, eF-seek, provides an interface to our search method. It simply requires a coordinate file in the PDB format, and generates a prediction result as a virtual complex structure, with the putative ligands in a PDB format file as the output. In addition, the predicted interacting interface is displayed to facilitate the examination of the virtual complex structure on our own applet viewer with the web browser (URL: http://eF-site.hgc.jp/eF-seek)

PreBI: prediction of biological interfaces of proteins in crystals

PreBI is a server that predicts biological interfaces in protein crystal structures, according to the complementarity and the area of the interface. The server accepts a coordinate file in the PDB format, and all of the possible interfaces are generated automatically, according to the symmetry operations given in the coordinate file. For all of the interfaces generated, the complementarities of the electrostatic potential, hydrophobicity and shape of the interfaces are analyzed, and the most probable biological interface is identified according to the combination of the degree of complementarity derived from the database analyses and the area of the interface. The results can be checked through an interactive viewer, and the most probable complex can be downloaded as atomic coordinates in the PDB format. PreBI is available at

Hepatocyte growth factor gene therapy reduces ventricular arrhythmia in animal models of myocardial ischemia.

It was recently reported that gene therapy using hepatocyte growth factor (HGF) has the potential to preserve cardiac function after myocardial ischemia. We speculated that this HGF gene therapy could also prevent ventricular arrhythmia. To investigate this possibility, we examined the antiarrhythmic effect of HGF gene therapy in rat acute and old myocardial infarction models. Myocardial ischemia was induced by ligation of the left descending coronary artery. Hemagglutinating virus of Japan (HVJ)-coated liposome containing HGF genes were injected directly into the myocardium fourteen days before programmed pacing. Ventricular fibrillation (VF)was induced by programmed pacing. The VF duration was reduced and the VF threshold increased after HGF gene therapy ( p&#60; 0.01). Histological analyses revealed that the number of vessels in the ischemic border zone was greatly increased after HGF gene injection. These findings revealed that HGF gene therapy has an anti-arrhythmic effect after myocardial ischemia.</p

CompDP: A Framework for Simultaneous Subgraph Counting Under Connectivity Constraints

The subgraph counting problem computes the number of subgraphs of a given graph that satisfy some constraints. Among various constraints imposed on a graph, those regarding the connectivity of vertices, such as "these two vertices must be connected," have great importance since they are indispensable for determining various graph substructures, e.g., paths, Steiner trees, and rooted spanning forests. In this view, the subgraph counting problem under connectivity constraints is also important because counting such substructures often corresponds to measuring the importance of a vertex in network infrastructures. However, we must solve the subgraph counting problems multiple times to compute such an importance measure for every vertex. Conventionally, they are solved separately by constructing decision diagrams such as BDD and ZDD for each problem. However, even solving a single subgraph counting is a computationally hard task, preventing us from solving it multiple times in a reasonable time. In this paper, we propose a dynamic programming framework that simultaneously counts subgraphs for every vertex by focusing on similar connectivity constraints. Experimental results show that the proposed method solved multiple subgraph counting problems about 10-20 times faster than the existing approach for many problem settings

Usefulness of body surface mapping to differentiate patients with Brugada syndrome from patients with asymptomatic Brugada syndrome.

We attempted to determine the usefulness of body surface mapping (BSM) for differentiating patients with Brugada syndrome (BS) from patients with asymptomatic Brugada syndrome (ABS). Electrocardiograms (ECG) and BSM were recorded in 7 patients with BS and 35 patients with ABS. Following the administration of Ic antiarrhythmic drugs, BSM was recorded in 5 patients with BS and 16 patients with ABS. The maximum amplitudes at J0, J20, J40 and J60 were compared between the 2 groups, as were 3-dimensional maps. The maximum amplitudes at J0, J20 and J60 under control conditions were larger in patients with BS than in patients with ABS (P < 0.05). A three-dimensional map of the ST segments under control conditions in patients with BS showed a higher peak of ST elevation in the median precordium compared to that for patients with ABS. Increases in ST elevation at J20, J40 and J60 following drug administration were greater in patients with BS than in patients with ABS (P < 0.05). Evaluation of the change in amplitude of the ST segment at E5 caused by Ic drug administration was also useful for differentiating between the 2 groups. In conclusion, BSM was useful for differentiating patients with BS from those with ABS.</p