Contents    ◾    vii

Chapter 3        De Novo Genome Assembly

89

3.1 INTRODUCTION TO DE NOVO GENOME ASSEMBLY

89

3.1.1

Greedy Algorithm

90

3.1.2

Overlap-Consensus Graphs

90

3.1.3

De Bruijn Graphs

91

3.2 EXAMPLES OF DE NOVO ASSEMBLERS

93

3.2.1

ABySS

93

3.2.2

SPAdes

97

3.3 GENOME ASSEMBLY QUALITY ASSESSMENT

99

3.3.1

Statistical Assessment for Genome Assembly

100

3.3.2

Evolutionary Assessment for De Novo Genome Assembly

103

3.4 SUMMARY

106

REFERENCES

107

Chapter 4        Variant Discovery

109

4.1 INTRODUCTION TO GENETIC VARIATIONS

109

4.1.1

VCF File Format

110

4.1.2. Variant Calling and Analysis

113

4.2 VARIANT CALLING PROGRAMS

114

4.2.1

Consensus-Based Variant Callers

114

4.2.1.1 BCF Tools Variant Calling Pipeline

115

4.2.2

Haplotype-Based Variant Callers

125

4.2.2.1 FreeBayes Variant Calling Pipeline

127

4.2.2.2 GATK Variant Calling Pipeline

129

4.3 VISUALIZING VARIANTS

143

4.4 VARIANT ANNOTATION AND PRIORITIZATION

143

4.4.1

SIFT

145

4.4.2

SnpEff

148

4.3.3

ANNOVAR

151

4.3.3.1 Annotation Databases

153

4.3.3.2 ANNOVAR Input Files

156

4.5 SUMMARY

160

REFERENCES

161