The Lingzhi Mushroom Genome

Preface
Contents
Contributors
Abbreviations
Abbreviation and Definition
1 Lingzhi, An Overview
	Abstract
	1.1 Introduction
		1.1.1 Overall Arrangement of the Book
		1.1.2 A Brief Account of Researches on Lingzhi, from Ancient China to the Modern Era
		1.1.3 Modern Research on Lingzhi
	1.2 Basic Biology
		1.2.1 Taxonomy and General Life Cycle of Lingzhi
		1.2.2 Worldwide Distribution of Wild G. Lucidum
		1.2.3 Cultivation and Industrial Productions.
	1.3 Genetic Studies
	1.4 The Chemical Components of Lingzhi
		1.4.1 Triterpenoids
		1.4.2 Meroterpenoids
		1.4.3 Ganoderma Steroids
		1.4.4 Alkaloids and Nucleosides
		1.4.5 Ganoderma Polysaccharides
	1.5 Bioactivities of Lingzhi’s Chemical Components
		1.5.1 Immunomodulatory Activity
		1.5.2 Antitumor Activity
		1.5.3 Hypoglycemic Activities
		1.5.4 Hepatoprotective Effect
		1.5.5 Anti-hyperlipidemia Effect
		1.5.6 Regulation of Intestinal Flora
	1.6 Pharmacological Effects of Lingzhi Preparations
		1.6.1 Antitumor Effect
		1.6.2 Immunoregulation Effect
		1.6.3 Protection and Treatment of Organ Damage
		1.6.4 Antiaging Effect and Antioxidant Activity
		1.6.5 Antibacterial and Anti-Inflammatory Effects
		1.6.6 Antiviral and Other Effects
	1.7 Clinical Application
	1.8 Legal Status of Lingzhi Mushroom
	1.9 Concluding Remarks
	Acknowledgements
	References
2 The Trend of Ganoderma Lucidum Research (1936–2019)
	Abstract
	2.1 Introduction
	2.2 Data Collection and Analytical Method
	2.3 Results
		2.3.1 Descriptive Analysis (Country, Author, Source)
		2.3.2 Thematic Analysis
		2.3.3 Co-Word Analysis
			2.3.3.1 Keyword Co-Occurrence
			2.3.3.2 Correspondence Analysis
		2.3.4 Co-Citation Analysis
			2.3.4.1 Papers Co-Citation Analysis
			2.3.4.2 Sources Co-Citation Analysis
		2.3.5 Collaboration Analysis
			2.3.5.1 Author Collaboration Network
			2.3.5.2 Institution Collaboration Network
			2.3.5.3 Country Collaboration Network
		2.3.6 Keyword Detection and Analysis
		2.3.7 Most Highly Cited Papers Analysis
	2.4 Conclusion and Discussion
	References
3 The Nuclear Genome of Lingzhi Mushroom
	Abstract
	3.1 Introduction
		3.1.1 Medical and Economic Significance of Ganoderma species
		3.1.2 Advantages of Whole-Genome Sequencing (WGS) Projects
	3.2 The current status of Ganoderma Nuclear Genome Whole-Genome Sequencing
	3.3 Genome Resources for Ganoderma Species
		3.3.1 Background
		3.3.2 Construction and content
	3.4 Discussion
	3.5 Conclusions
	References
4 Lingzhi Mitochondrial Genome
	Abstract
	4.1 General Introduction
		4.1.1 Concept
		4.1.2 Principle
			4.1.2.1 Mitochondrial Origin
			4.1.2.2 Mitochondrial Structure
			4.1.2.3 Mitochondrial Genetics
			4.1.2.4 Mitochondrial Evolution
			4.1.2.5 Mitochondrial Function
		4.1.3 Research Methods For Mitochondrial Genome Analysis
			4.1.3.1 Molecular Experiments
				DNA Extraction
				Next-Generation Sequencing
			4.1.3.2 Data Analyses
				Mitochondrial Genome Assembly and Annotation
				Phylogenomic Analysis
	4.2 Progress of Lingzhi Mitochondrial Genome
		4.2.1 Structure of Lingzhi Mitochondrial Genome
		4.2.2 Evolution of Mitochondrial Genome in Genus Ganoderma
			4.2.2.1 Mitochondrial Genome of Ganoderma meredithiae
			4.2.2.2 Mitochondrial Genome of Ganoderma applanatum
			4.2.2.3 Mitochondrial Genome of Ganoderma sinense
			4.2.2.4 Mitochondrial Genome of Ganoderma tsugae
			4.2.2.5 Mitochondrial Genome of Ganoderma calidophilum
			4.2.2.6 Mitochondrial Genome of Ganoderma leucocontextum
			4.2.2.7 Mitochondrial Phylogenomics of Ganoderma
	4.3 Future Perspective
		4.3.1 Problems
		4.3.2 Topics of Interests
	Acknowledgements
	References
5 Transcriptome of Lingzhi
	Abstract
	5.1 Introduction
	5.2 Method for Transcriptome Analysis of G. Lucidum
		5.2.1 cDNA-Amplified Fragment Length Polymorphism Method for Transcription Profiling
		5.2.2 Expressed Sequence Tags from a cDNA Library
		5.2.3 RNA Sequencing
	5.3 The Workflow of RNA-Seq Data Analysis
		5.3.1 Quality Control of Reads
		5.3.3 Mapping Reads to the Reference Genome
		5.3.4 New Transcript Prediction and Quantification
		5.3.5 Identification of Differential Expression Genes (DEGs)
		5.3.6 Enrichment Analysis of DEGs
			5.3.6.1 KEGG Pathway Annotation of DEGs
			5.3.6.2 KEGG Enrichment Analysis of DEGs
			5.3.6.3 GO Term Annotation of DEGs
			5.3.6.4 GO Term Enrichment Analysis of DEGs 
		5.3.7 Alternative Splicing Analysis
		5.3.8 Single Nucleotide Polymorphism and Insertion-Deletion Analysis
	5.4 Transcriptome Analysis of Genus Ganoderma
		5.4.1 Responses to Environmental Factors
		5.4.2 Transcriptome Analysis of Particular Tissues and Developmental Stages
		5.4.3 Transcriptome Analysis of Oil Palm Pathogen Ganoderma Boninense
		5.4.4 Transcriptome Analysis of Ganoderic Acid Biosynthesis
		5.4.5 RNA-Editing Events in the G. Lucidum
	5.5 Concluding Remarks
	Acknowledgements
	References
6 Proteomic Characterization of Lingzhi
	Abstract
	6.1 Overview of the Ganoderma lucidum Proteomics
	6.2 Differential Proteomics Research
	6.3 Proteomics and Multi-omics Integration Analysis
	6.4 Advantages and Disadvantages of Ganoderma lucidum Proteomics
	6.5 Concluding Remarks
	References
7 Noncoding RNAs in Lingzhi Mushroom
	Abstract
	7.1 Introduction
	7.2 LincRNAs in Lingzhi Mushroom
		7.2.1 The Bioinformatic Pipeline for LincRNA Identification
		7.2.2 The Modified 3’ RACE Method for Determination of Transcriptional Orientation of LincRNAs
		7.2.3 Possible Action Mechanisms of LincRNAs in Lingzhi Mushroom
	7.3 NATs in Lingzhi Mushroom
		7.3.1 Identification of Lingzhi NATs
		7.3.2 Characterization of Lingzhi NATs
		7.3.3 Possible Functions of Lingzhi NATs
	7.4 CircRNAs in Lingzhi Mushroom
		7.4.1 Strategies for the Identification of Lingzhi CircRNAs
		7.4.2 Validation of Lingzhi CircRNAs
		7.4.3 Possible Functions of CircRNAs in Lingzhi Mushroom
	7.5 MilRNAs in Lingzhi Mushroom
		7.5.1 Identification of Lingzhi MilRNAs
		7.5.2 Characterization of Lingzhi milRNAs
		7.5.3 Validation of the Predicted milRNAs Using Stem-loop RT-PCR and Sanger Sequencing
		7.5.4 Validation of the Predicted milRNAs Using Bioinformatic Analyses
		7.5.5 Possible Functions of Lingzhi milRNA
	7.6 Concluding Remarks
	Acknowledgements
	References
8 Biosynthetic Pathway and Signal Transduction Regulation of Ganoderic Acid Biosynthesis in Lingzhi
	Abstract
	8.1 Biosynthetic Pathway of Ganoderic Acid
	8.2 Environmental Regulation of Ganoderic Acid Biosynthesis
		8.2.1 Nutritional Conditions Regulate GA Biosynthesis
			8.2.1.1 Carbon Source
			8.2.1.2 Nitrogen Source
			8.2.1.3 Intermediate Metabolites
		8.2.2 Physical Means Regulate GA Biosynthesis
			8.2.2.1 Temperature
			8.2.2.2 Solid-Medium Culture Approach
			8.2.2.3 PH
			8.2.2.4 Light
		8.2.3 Single Chemical or Biological Signals Regulate GA Biosynthesis
			8.2.3.1 Methyl Jasmonate, Salicylic Acid, and Ethylene
			8.2.3.2 Phenobarbital, Aspirin, and Acetic Acid
			8.2.3.3 Metal Ions (Na+ and Cu2+)
			8.2.3.4 Cellulase and Microcrystalline Cellulose
	8.3 Role of Signaling in GA Biosynthesis Regulation
		8.3.1 Reactive Oxygen Species
		8.3.2 Ca2+
		8.3.3 CAMP
		8.3.4 H2S
	8.4 Membrane Fluidity and PLD-Phosphatidic Acid Signaling
	8.5 Crosstalk of Different Signals for GA Biosynthesis
	8.6 Locus/Target of Signals in the Regulation of GA Biosynthesis
	8.7 Concluding Remarks
	References
9 Genetic Transformation System
	Abstract
	9.1 Introduction
	9.2 Genetic Transformation Methods
		9.2.1 PMT
		9.2.2 REMI
		9.2.3 Electroporation
		9.2.4 ATMT
	9.3 Application of Genetic Transformation of G. Lucidum
		9.3.1 Efficient Production of Polysaccharides by Genetic Engineering of G. Lucidum
		9.3.2 Efficient Production of Ganoderic Acid by Genetically Modified G. Lucidum
	9.4 Gene Silencing
	9.5 Recent Advances in the Disruption and Deletion of Target Genes in G. Lucidum
	9.6 Concluding Remarks
	Acknowledgements
	References
10 Chemical Components and Cancer Immunotherapy of Ganoderma
	Abstract
	10.1 Chemical Components
		10.1.1 Triterpenoids
		10.1.2 Meroterpenoids
		10.1.3 Polysaccharides
		10.1.4 Others
	10.2 Cancer Immunotherapy
		10.2.1 Bioactive Compounds of Ganoderma and Their Immunomodulatory Effect on Cancer Treatment
			10.2.1.1 Fungal Immunomodulation Proteins
			10.2.1.2 Effects of Polysaccharides
		10.2.2 Pathways in Immune Cells Implicated in the Cancer Immunotherapy by Ganoderma
			10.2.2.1 T-Lymphocytes and Dendritic Cell
			10.2.2.2 Natural Killer Cells and B Lymphocytes
			10.2.2.3 Macrophage
	10.3 Clinical Studies, Toxicology, and Discussion
		10.3.1 Clinical Studies
		10.3.2 Toxicity
		10.3.3 Discussion
	References
11 A Comprehensive Meta-Analysis on the Effectiveness and Safety of Lingzhi
	Abstract
	11.1 Introduction
	11.2 An Introduction to Meta-Analysis
		11.2.1 Basic Terminology
		11.2.2 A Brief History of Meta-Analysis
	11.3 Procedures of Conducting Meta-Analysis
		11.3.1 Searching the Literature
		11.3.2 Coding Studies Characteristics
			11.3.2.1 Inclusion and Exclusion Criteria
			11.3.2.2 Developing a Coding Guide
			11.3.2.3 Selecting and Training Coders
		11.3.3 Analyzing Data
			11.3.3.2 Meta-Analysis
		11.3.4 Addressing Reporting Bias
			11.3.4.1 Reporting Bias
		11.3.5 Reporting Results
	11.4 Meta-Analysis on the Effectiveness of Lingzhi
	11.5 Meta-Analysis on the Safety of Lingzhi
	11.6 Concluding Remarks
	References
12 Survey of Lingzhi Health Foods and Drugs
	Abstract
	12.1 Introduction
	12.2 Data and Methods
		12.2.1 Data Source
		12.2.2 Data Analysis
	12.3 Results
		12.3.1 Number Increase of Health Foods and Drugs by Time
		12.3.2 Statistics of the Approved Lingzhi Health Foods and Drugs
			12.3.2.1 Tissue Parts Used in Lingzhi Single and Multiple Composition Health Foods and Drugs
			12.3.2.2 Health Effects of Lingzhi Health Foods and Drugs
			12.3.2.3 Marker Components of Lingzhi Health Foods and Drugs
			12.3.2.4 Types of the Dosage Forms
		12.3.3 Usage Frequency of Raw Materials in the Approved Lingzhi Health Foods and Drugs
		12.3.4 Analysis of the Combination of Lingzhi and Other Medicinal Materials
	12.4 Discussions
		12.4.1 Current Status and Deficiencies of Lingzhi Health Foods and Drugs
		12.4.2 The Future Development of Medicinal Materials
			12.4.2.1 Catalogue of Exempt Raw Material for Health Foods
			12.4.2.2 Development of New Health Effects Catalog
	12.5 Concluding Remarks
	References