WGS/WES Pipeline
Sections:
WGS/WES Variant Calling Pipeline
Overview
Use Cases
Supported Data Types
When to Choose WGS vs WES
Design Principles
High-Level Workflow
Inputs and Outputs
Quality, Coverage, and QC
Filtering Strategy Notes
Reference and Resource Recommendations
Reproducibility & Execution
Data Stewardship & Compliance
Limitations & Non-Goals
What’s Next
Run the WGS/WES Pipeline
Pipeline Inputs & Layout
Step-by-Step Workflow
1) Raw Read QC
2) Adapter/Quality Trimming (optional but recommended for WES)
3) Alignment to Reference
4) Duplicate Marking & BQSR
5) Variant Calling
6) Variant Filtering
7) Annotation
8) Cohort-Level QC & Reports
Parallelization & Performance
WES-Specific Notes
Expected Outputs
Troubleshooting
Next Steps
Advanced Analysis
Trio and Family-Based Analysis
Joint Calling for Large Cohorts
Copy Number Variation (CNV) Analysis
Mitochondrial Variant Analysis
Tumor Purity Estimation & Adjustment
Integration and Reporting
Next Steps
Annotated Examples & Interpretation
Example: Tumor–Normal Variant Calling
Example: Tumor-Only Variant Calling
Example: Germline Variant Calling
Pipeline Structure and Containerisation
Modular Workflow Overview
Support for Germline and Somatic Calling
Containerisation
Scalability and Workflow Automation
Example Directory Layout
Best Practices for Execution
Stage-to-Tool Mapping With Example Commands
Example Commands (Bash)
Reproducibility Checklist
Case Study: ITH-aware Somatic Interpretation for WGS/WES
What Was Built
Cohort Profiling and Heterogeneity
Drug Screening and Response Definition
Expression Signatures Predicting Response
Mechanism of Lenvatinib Resistance & Combination Strategy
ITH-aware Somatic Interpretation & Recommendations
Limitations
Case Study: WES in Relapsing CLL: RPS15 Mutations and Clonal Evolution
What Was Built
Cohort Profiling and Heterogeneity
Genomic Profiling Methods (WES Focus)
Drug Screening and Response Definition
Expression Signatures Predicting Response
Mechanism of Relapse & Targeted Strategies
Clonal Evolution-Aware Somatic Interpretation & Recommendations
Limitations
References
Primary Study
Supporting Literature
Databases and Resources
WGS/WES Pipeline
Index
Index