Physics of System Biology

The course syllabus and Note

What's New in this Course ?

經過分子生物學與生物物理數十年的進展，科學界對生物分子與次細胞單元的功能已有初步瞭解。在未來十年的後基因體時代，最重要且急迫性的研究課題將是從系統觀點探討細胞、器官以至生物網路系統的分子層次機制，並利用這些新知識與衍生的新技能促進人類福祉。然而這是跨領域的科技發展，需要非侷限於傳統領域的新專長。光學在生醫領域已有實質影響，未來若能結合基因工程技術於探討生物網路在特定干擾下的即時反應模式，將可進一步深化光學在生醫領域的貢獻。
本課程將應用電腦圖學與網路科學的進展於生命體系，從系統觀點介紹生物網路的架構、網路主題(network motifs)與其相關功能。 修課學生在完成本課程後，應具有系統生物物理基礎，能進行生物網路分析以發現網路之重要模組、規劃研究策略以驗證或改善網路架構之正確性、並進一步發展有效的光學研究策略以探討生物網路在特定干擾後之反應模式。


Course History:

(1) January 15, 2013-June 15, 2013

Lecture notes have been posted whenever possible.  Not all lectures are available for distribution.

Textbook and reference books
An Introduction to Systems Biology by Uri Alon

Network analysis and visualization software
Cytoscape

LEC #

TOPICS

1

Chapter 1 Fundamental of Physics of System Biology

From Omics Technology to System Biology Perspective (以系統觀點介紹生命過程、生物網路系統與量測技術) (Lecture Note: pdf PDF - 2.0 MB)

1.1 Overview on Physics of System Biology

1.2 High-Throughput Technologies: Next Generation Sequencing Technologies, Transcriptomics, Proteomics, and Metabolomics

1.3 Biological Networks: Transcriptional Regulatory Networks, Protein-Protein Interaction Networks, Metabolic Networks, Signaling Networks

1.4 Mathematical Modeling for Understanding Complex Biological Processes: Modeling Metabolic Processes, Modeling gene regulatory networks

Workshop 1: Search the Databases on Web Servers---pdf PDF 68 kB

2

Chapter 2 Network Properties and Measures

Network topology, motifs and measures of biological networks (介紹生物網路架構與量化參數的計算方法) (Lecture Note: pdf PDF - 211 kB)

2.1 Overview

2.2 Graph Theory and Definitions

2.3 Network Measures: Local Network Measures, Global Network Measures

2.4 Network Models: random networks, small-world networks, scale-free networks

2.5 Integration of Networks and Data

Workshop 2: Network Analysis and Identification of Clusters/Complexes---pdf PDF 40 kB

Workshop 3: Data Integration with a Network---pdf PDF 167 kB

Homework 1---Due: March 1, 2014

3

Chapter 3 Basic Concepts of Transcriptional Networks (TN) and the relevant Motifs

(介紹轉錄調制網路與相關網路主題) (Lecture Note: pdf PDF - 839 kB)

3.1Basic Concepts of Transcriptional Networks

3.2 The Input Functions: The Hill Function, The Logic Input Function, The Multi-dimensional Input Function

3.3 Response Time of a Simple Gene Regulation and Temporal Patterns of Signaling Networks

3.4 Network Motifs and Relevant Functions

Workshop 4: Functional Analysis and Gene Enrichment in Pathway---pdf PDF 44 kB

4

Chapter 4 Network Motifs of Autoregulation (AR) and Feed Forward Loop (FFL)

(自我调節, 延遲/加速響應, 與產生脈衝之主題和相關功能) (Lecture Note: pdf PDF - 784 kB)

4.1 Negative AR (NAR) Motif Speeds the Response Times of Transcription Networks

4.2 NAR Motif Enhances Stability in Gene Networks

4.3 Coherent FFL (cFFL) Motif Serves as a Sign Sensitive Delay Element

4.4 cFFL Motif with a SUM Input Prolongs Flagella Expression in E. Coli

4.5 Incoherent FFL (iFFL) Produces a Pulse-Generating Gene Expression

4.6 iFFL Accelerates the Response Time of the Gal System in E. Coli

5

Chapter 5 Single Input Module (SIM) and Toggle Switch (介紹單輸入模組與撥動開關之網路主題和相關功能)

(Lecture Note: pdf PDF - 1.2 MB)

5.1 Timing Program of Gene Expression in a Flagella Pathway (Ref: pdf PDF)

5.2 Just-in-Time Transcription Program in Metabolic Pathways

5.3 An All-or-None Genetic Switch

5.4 Genetic Toggle Switch in E. Coli

5.5 Noise Propagation in Gene Networks

Homework 2---Due: April 1, 2014

6

Chapter 6 Circadian Oscillatory Motif (介紹生理時鐘網路主題和相關功能 ) (pdf PDF - 183 kB)

6.1 A Cyclic Negative-feedback Loop Oscillatory Motif

6.2 An Activator-Repressor Noise-Tolerative Clock Motif

6.3 Case 1: Ordered Phosphorylation Governs Three-Protein Circadian Clock

6.4 Case 2: Light-Driven Cyanobacterial Circadian Oscillator

7

Chapter 7 Kinetic Proof-reading (生命過程之動力校對原理) (pdf PDF - 183 kB)

7.1 A New Mechanism for Reducing Errors in Biosynthetic Processes: the Principle of Kinetic Proofreading (Ref: pdf PDF)

7.2 Kinetic Proofreading in Signal Transduction

7.3 Kinetic Proofreading of Gene Activation by Chromatin Remodeling

8

Chapter 8 Robustness in Biological Networks (介紹生物網路之強健性) (pdf PDF - 880 kB)

Robustness in Biochemical Networks

8.1 Robustness in Simple Biochemical Networks

8.2 Robustness in Bacterial Chemotaxis

8.3 Interactions between Receptors Produce Ultra Sensitivity and Thermal Robustness of Signaling in Bacterial Chemotaxis


Robustness in Development

8.4 Robustness of Developmental Precision in the Drosophila Embryo

8.5 The Limits to Positional Information

Workshop 5: ---pdf PDF 840 kB

Homework 3---Due: May 1, 2014

9

Chapter 9 Adaptive Evolution and Optimality (生物適應性進化和最佳化) (pdf PDF - 183 kB)

9.1 Adaptive Evolution of E. coli to Optimal Growth

9.2 Optimality and Evolutionary Tuning of the Expression Level of a Protein

Homework 4---Due: June 1, 2014

10

Chapter 10 Overview of Human Disease Networks (人類疾病之網路概念與應用) (pdf PDF - 183 kB)

10.1 Architecture of the Human Regulatory Network

10.2 Network Medicine: Basic Concepts

10.3 Cancer Genome Analysis

Workshop 6: ---pdf PDF 840 kB