26,245 research outputs found
Allo-network drugs: Extension of the allosteric drug concept to protein-protein interaction and signaling networks
Allosteric drugs are usually more specific and have fewer side effects than orthosteric drugs targeting the same
protein. Here, we overview the current knowledge on allosteric signal transmission from the network point of view, and show that most intra-protein conformational changes may be dynamically transmitted across protein-protein interaction and signaling networks of the cell. Allo-network drugs influence the pharmacological target protein indirectly using specific inter-protein network pathways. We show that allo-network drugs may have a higher efficiency to change the networks of human cells than those of other organisms, and can be designed to have specific effects on cells in a diseased state. Finally, we summarize possible methods to identify allo-network drug targets and sites, which may develop to a promising new area of systems-based drug design
A Field Guide to Genetic Programming
xiv, 233 p. : il. ; 23 cm.Libro ElectrĂłnicoA Field Guide to Genetic Programming (ISBN 978-1-4092-0073-4) is an introduction to genetic programming (GP). GP is a systematic, domain-independent method for getting computers to solve problems automatically starting from a high-level statement of what needs to be done. Using ideas from natural evolution, GP starts from an ooze of random computer programs, and progressively refines them through processes of mutation and sexual recombination, until solutions emerge. All this without the user having to know or specify the form or structure of solutions in advance. GP has generated a plethora of human-competitive results and applications, including novel scientific discoveries and patentable inventions. The authorsIntroduction --
Representation, initialisation and operators in Tree-based GP --
Getting ready to run genetic programming --
Example genetic programming run --
Alternative initialisations and operators in Tree-based GP --
Modular, grammatical and developmental Tree-based GP --
Linear and graph genetic programming --
Probalistic genetic programming --
Multi-objective genetic programming --
Fast and distributed genetic programming --
GP theory and its applications --
Applications --
Troubleshooting GP --
Conclusions.Contents
xi
1 Introduction
1.1 Genetic Programming in a Nutshell
1.2 Getting Started
1.3 Prerequisites
1.4 Overview of this Field Guide I
Basics
2 Representation, Initialisation and GP
2.1 Representation
2.2 Initialising the Population
2.3 Selection
2.4 Recombination and Mutation Operators in Tree-based
3 Getting Ready to Run Genetic Programming 19
3.1 Step 1: Terminal Set 19
3.2 Step 2: Function Set 20
3.2.1 Closure 21
3.2.2 Sufficiency 23
3.2.3 Evolving Structures other than Programs 23
3.3 Step 3: Fitness Function 24
3.4 Step 4: GP Parameters 26
3.5 Step 5: Termination and solution designation 27
4 Example Genetic Programming Run
4.1 Preparatory Steps 29
4.2 Step-by-Step Sample Run 31
4.2.1 Initialisation 31
4.2.2 Fitness Evaluation Selection, Crossover and Mutation Termination and Solution Designation Advanced Genetic Programming
5 Alternative Initialisations and Operators in
5.1 Constructing the Initial Population
5.1.1 Uniform Initialisation
5.1.2 Initialisation may Affect Bloat
5.1.3 Seeding
5.2 GP Mutation
5.2.1 Is Mutation Necessary?
5.2.2 Mutation Cookbook
5.3 GP Crossover
5.4 Other Techniques 32
5.5 Tree-based GP 39
6 Modular, Grammatical and Developmental Tree-based GP 47
6.1 Evolving Modular and Hierarchical Structures 47
6.1.1 Automatically Defined Functions 48
6.1.2 Program Architecture and Architecture-Altering 50
6.2 Constraining Structures 51
6.2.1 Enforcing Particular Structures 52
6.2.2 Strongly Typed GP 52
6.2.3 Grammar-based Constraints 53
6.2.4 Constraints and Bias 55
6.3 Developmental Genetic Programming 57
6.4 Strongly Typed Autoconstructive GP with PushGP 59
7 Linear and Graph Genetic Programming 61
7.1 Linear Genetic Programming 61
7.1.1 Motivations 61
7.1.2 Linear GP Representations 62
7.1.3 Linear GP Operators 64
7.2 Graph-Based Genetic Programming 65
7.2.1 Parallel Distributed GP (PDGP) 65
7.2.2 PADO 67
7.2.3 Cartesian GP 67
7.2.4 Evolving Parallel Programs using Indirect Encodings 68
8 Probabilistic Genetic Programming
8.1 Estimation of Distribution Algorithms 69
8.2 Pure EDA GP 71
8.3 Mixing Grammars and Probabilities 74
9 Multi-objective Genetic Programming 75
9.1 Combining Multiple Objectives into a Scalar Fitness Function 75
9.2 Keeping the Objectives Separate 76
9.2.1 Multi-objective Bloat and Complexity Control 77
9.2.2 Other Objectives 78
9.2.3 Non-Pareto Criteria 80
9.3 Multiple Objectives via Dynamic and Staged Fitness Functions 80
9.4 Multi-objective Optimisation via Operator Bias 81
10 Fast and Distributed Genetic Programming 83
10.1 Reducing Fitness Evaluations/Increasing their Effectiveness 83
10.2 Reducing Cost of Fitness with Caches 86
10.3 Parallel and Distributed GP are Not Equivalent 88
10.4 Running GP on Parallel Hardware 89
10.4.1 Master–slave GP 89
10.4.2 GP Running on GPUs 90
10.4.3 GP on FPGAs 92
10.4.4 Sub-machine-code GP 93
10.5 Geographically Distributed GP 93
11 GP Theory and its Applications 97
11.1 Mathematical Models 98
11.2 Search Spaces 99
11.3 Bloat 101
11.3.1 Bloat in Theory 101
11.3.2 Bloat Control in Practice 104
III
Practical Genetic Programming
12 Applications
12.1 Where GP has Done Well
12.2 Curve Fitting, Data Modelling and Symbolic Regression
12.3 Human Competitive Results – the Humies
12.4 Image and Signal Processing
12.5 Financial Trading, Time Series, and Economic Modelling
12.6 Industrial Process Control
12.7 Medicine, Biology and Bioinformatics
12.8 GP to Create Searchers and Solvers – Hyper-heuristics xiii
12.9 Entertainment and Computer Games 127
12.10The Arts 127
12.11Compression 128
13 Troubleshooting GP
13.1 Is there a Bug in the Code?
13.2 Can you Trust your Results?
13.3 There are No Silver Bullets
13.4 Small Changes can have Big Effects
13.5 Big Changes can have No Effect
13.6 Study your Populations
13.7 Encourage Diversity
13.8 Embrace Approximation
13.9 Control Bloat
13.10 Checkpoint Results
13.11 Report Well
13.12 Convince your Customers
14 Conclusions
Tricks of the Trade
A Resources
A.1 Key Books
A.2 Key Journals
A.3 Key International Meetings
A.4 GP Implementations
A.5 On-Line Resources 145
B TinyGP 151
B.1 Overview of TinyGP 151
B.2 Input Data Files for TinyGP 153
B.3 Source Code 154
B.4 Compiling and Running TinyGP 162
Bibliography 167
Inde
Biological control networks suggest the use of biomimetic sets for combinatorial therapies
Cells are regulated by networks of controllers having many targets, and
targets affected by many controllers, but these "many-to-many" combinatorial
control systems are poorly understood. Here we analyze distinct cellular
networks (transcription factors, microRNAs, and protein kinases) and a
drug-target network. Certain network properties seem universal across systems
and species, suggesting the existence of common control strategies in biology.
The number of controllers is ~8% of targets and the density of links is 2.5%
\pm 1.2%. Links per node are predominantly exponentially distributed, implying
conservation of the average, which we explain using a mathematical model of
robustness in control networks. These findings suggest that optimal
pharmacological strategies may benefit from a similar, many-to-many
combinatorial structure, and molecular tools are available to test this
approach.Comment: 33 page
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