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Toward Automatically Drawn Metabolic Pathway Atlas with Peripheral Node Abstraction AlgorithmPowerPoint Presentation

Toward Automatically Drawn Metabolic Pathway Atlas with Peripheral Node Abstraction Algorithm

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Toward Automatically Drawn Metabolic Pathway Atlas with Peripheral Node Abstraction Algorithm

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Toward Automatically Drawn Metabolic Pathway Atlas with Peripheral Node Abstraction Algorithm

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Toward Automatically Drawn Metabolic Pathway Atlas with Peripheral Node Abstraction Algorithm

Myungha Jang, ArangRhie, and Hyun-Seok Park*

Bioinformatics Laboratory, School of Engineering

EwhaWomans University

Seoul, Korea

IEEE BIBM, 18-21 Dec 2010, Hong Kong

EwhaWomans University

Table of Contents

Introduction

Topological Nature of Metabolic Networks at Peripheral Nodes

Node Abstraction Featured Scale-free Algorithm

Experimental Results

Discussion and Future Work

IEEE BIBM, 18-21 Dec 2010, Hong Kong

EwhaWomans University

I. INTRODUCTION

Automatic graph layout algorithms in systems biology

- Abstract graph structure ⇒ visual representation
- Graphical diagrams are intuitively helpful to understand biochemical reaction networks
- - Node : compound, Edge : reactions

- Optimal solutions : NP-hard problems

IEEE BIBM, 18-21 Dec 2010, Hong Kong

EwhaWomans University

I. INTRODUCTION

Focusing on Global Metabolic Pathway

- A complete metabolic network indicates all the metabolic potential and capacity.
- The shift of research focus: single pathways to multiple pathways.
- Visualization serves an important role in understanding large scale metabolic network.
- KEGGAtlas(http://www.genome.ad.jp/kegg), 2008
- Terms : Global (metabolic) pathway, Multiple pathway, Atlas

IEEE BIBM, 18-21 Dec 2010, Hong Kong

EwhaWomans University

I. INTRODUCTION

Our Efforts Toward Automatic Global Layout

- Not enough to deal with the global pathway!
- How can we obtain a complete view?
- No attempts for automatic visualization for Atlas

IEEE BIBM, 18-21 Dec 2010, Hong Kong

EwhaWomans University

I. INTRODUCTION

How To Deal With Large-scale Metabolic Pathway?

- Related work: KEGG Atlas
- The map integration process is carried out manually by curators.
- Based on curator’s experience
- However, that metabolic networks are dynamic in nature should not be disregarded Systematic approach is necessary

IEEE BIBM, 18-21 Dec 2010, Hong Kong

EwhaWomans University

INTRODUCTION

How To Deal With Large-scale Metabolic Pathway? (con’d)

- Our Strategy
- We provide a novel algorithmic approach in drawing multiple metabolic pathways by considering two properties:
- 1. Automatic abstraction criteria: by analyzing a topological nature of metabolic networks based on the graphical property of relation distance, linear reactions were abstracted as a unit reaction.
- 2. the consistency of highly connected nodes

II. Topological Nature of Metabolic Networks at Peripheral Nodes

- We obtained 255 map data by parsing KEGG XML (KGML) documents of version 0.6 using our KGML Parser.

+

KGML

Two terms were defined:

1. Relation degree

the number of edges branching from a node

2. Relation distance

a factor to measure the length between any two compounds encompassing nodes which all have relation degrees less than or equal to p (p = 2)

- A dedicated analysis on peripheral nodes with low connectivity was performed.

IEEE BIBM, 18-21 Dec 2010, Hong Kong

EwhaWomans University

II. Topological Nature of Metabolic Networks at Peripheral Nodes

Relation Distance Term Clarification

- Definition: The length between any two compounds encompassing nodes which all have relation degrees equal to p
- Here, p = 2

IEEE BIBM, 18-21 Dec 2010, Hong Kong

EwhaWomans University

II. Topological Nature of Metabolic Networks at Peripheral Nodes

Relation Distance Example in Map

RD(C01290, C00369) = 7

- cpd:C01291

- cpd:C01290

- cpd:C16466

- cpd:C16475

- cpd:C16468

- cpd:C16470

- cpd:C16471

- cpd:C16469

- cpd:C00369

IEEE BIBM, 18-21 Dec 2010, Hong Kong

EwhaWomans University

III. Node Abstraction Featured Scale-free Algorithm

Basic Motivation

- Observation: 66.83% of the total compounds within the complete metabolic pathways were of low connectivity, with less than relation degree of 3.
- The number of compounds with higher relation degree, i.e. more than 6 edges, was much less.

Abstracting Compounds With Linear Interaction

Layout Components according to High Connectivity

IEEE BIBM, 18-21 Dec 2010, Hong Kong

EwhaWomans University

III. Node Abstraction Featured Scale-free Algorithm

A. Abstracting Compounds With Linear Interaction

- We abstracted and hid all those compounds that appear within these linear interactions.
- This approach could be called “chain reduction”(M. Chimaniet al)
- All green compounds in the figure will be hidden in the graph layout according to this approach.

IEEE BIBM, 18-21 Dec 2010, Hong Kong

EwhaWomans University

III. Node Abstraction Featured Scale-free Algorithm

B. Layout Components according to High Connectivity

- Highly Connected Nodes: Nodes with relation degree bigger than 6
- LayoutHighConnectedNode()Algorithm Steps
- Find a highly Connected node Nd
- Each component connected to Nd is decomposed into sub-graph
- Each decomposed sub-graph is treated as a super node to apply the spring-embedding algorithm

- Input : Metabolic Pathway Graph
- Output : coordinates of each node
- voidLayoutPathway(Pathway graph)
- {
- IF highly connected nodes (Nd) exist in graph
- LayoutHighlyConnectedNode(graph, Nd);
- ELSEIF any cycle(Nc) exists in graph
- AND size of cycle ≥ 6
- LayoutCircular(graph, Nc);
- ELSELayoutHierarchic(graph);
- }

6

3

IEEE BIBM, 18-21 Dec 2010, Hong Kong

EwhaWomans University

IV. Experimental results

- Experiments : To compare compression rate of compounds, we obtained the number of abstracted compounds and edge crossings by applying two different layout algorithms:
- Result 1
- Node compression rate performance
- Scope
- 1. 84 single metabolic pathways
- 2. 8 major categorized metabolic pathways
- 3. the global pathway
- Result 2
- The number of edge crossing comparison between by
- 1. Conventional algorithm
- 2. Our Node abstraction featured scale-free layout algorithm

Categorized pathways

Global

pathway

…

…

single pathways

IEEE BIBM, 18-21 Dec 2010, Hong Kong

EwhaWomans University

III. Experimental results

Peripheral path as supplementary nodes

Result 1B

The Number of Nodes Before and After Applying Node Abstraction

IEEE BIBM, 18-21 Dec 2010, Hong Kong

EwhaWomans University

III. Experimental results

Peripheral path as super edges

Result 1A

Original Network Abstracted Network

Results drawn with Cytoscape, using conventional spring embedding

The red-colored edges represent the abstracted edges. (abstraction rate : 70%)

IEEE BIBM, 18-21 Dec 2010, Hong Kong

EwhaWomans University

III. Experimental results

Result 2 : Edge Crossing Reduction

- In single metabolic pathways, the node abstraction featured algorithm reduced edge crossings by 63.31%.
- In a global metabolic pathway, the number of edge crossings has reached a reduction of 58.08% in total.
- Our proposed algorithm with node abstraction resulted in 86,067 edge crossings, whereas the one without node abstraction resulted in 205,316 edge crossings.

IEEE BIBM, 18-21 Dec 2010, Hong Kong

EwhaWomans University

IV. Discussion

- Two approaches were used:
- 1. Abstracting compound pairs according to a consistent criteria
- 2. Layout components according to high connectivity
- Our experimental results show that node abstraction feature reduced the number of compounds by approximately 23% in global pathway.
- Further discussion is necessary regarding enzyme reactions

IEEE BIBM, 18-21 Dec 2010, Hong Kong

EwhaWomans University

IV. Why is our work important?

- The first systematic approach for Atlas visualization focusing on peripheral nodes
- Fundamental to building a hierarchical structure of Atlas
- Our approach is flexible upon pathway database change that frequently updates
- It is a crucial preliminary step toward automatically drawn metabolic pathway
- Future research on individual biological meaning of each peripheral nodes and abstracted path

IEEE BIBM, 18-21 Dec 2010, Hong Kong

EwhaWomans University