ACMG clinical laboratory standards for next-generation sequencing (2013)

2013にAmerican College of Medical Geneticsが出したNGSの臨床利用に関するガイドライン
遅まきながらメモ
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構成を書き出すだけでも一苦労ですが…
基本的には留意点の網羅的列挙となっており、実用にあたっては、遺伝学者・臨床家・臨床検査家が注意深く活用し、発展していくことが求めらる、という段階です
ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencingは、臨床的に行われたゲノムワイドシークエンシングによって、二次的に・意図せずに見つかる遺伝的ファインディングズについての推奨について
- これが書かれた時点で「56 genes」については、患者の希望に応じて、伝える/伝えない、を必須とするべきなのかどうか、などについてのペイパーです
- これらについては次の記事(こちら)
さて：ACMG clinical laboratory standards for next-generation sequencing (2013)
- A. Introduction
  - 概論
  - A.1. Disease-targeted gene panels
  - A.2. Exome sequencing
  - A.3. Genome sequencing
- B. Overview of NGS
  - 概論
  - B.1. Sample preparation
  - B.2. Library generation
  - B.3. Barcoding
  - B.4. Target enrichment
  - B.5. Sequencing platforms
  - B.6. Data analysis
- C. Test Ordering
  - 概論
- D. Upfront Considerations for Test Development
  - D.1. Test content
    - D.1.1. Disease-targeted gene panels
    - D.1.2. Exome and genome sequencing
  - D.2. Choice of sequencer and sequencing methods
  - D.3. Choice of data analysis tools
    - D.3.1. Base calling
    - D.3.2. Read alignment
    - D.3.3. Variant calling
    - D.3.4. File formats
  - D.4. Variant filtering
    - D.4.1. Disease-targeted panels
    - D.4.2. Exome and genome sequencing
  - D.5. Sequencing regions with homology
  - D.6. Companion technologies and result confirmation
- E. Test Development and Validation
  - E.1. General considerations
    - E.1.1. Test development and platform optimization
    - E.1.2. Test validation
    - E.1.3. Platform validation
    - E.1.4. Quality management
  - E.2. Data analysis optimization
    - E.2.1. Coverage
    - E.2.2. Allelic fraction and zygosity
  - E.3. Determination of performance parameters
    - E.3.1. Analytical sensitivity
    - E.3.2. Analytical specificity
    - E.3.3. FN and FP rates
    - E.3.4. Clinical sensitivity
    - E.3.5. Assay robustness
    - E.3.6. Assay precision
    - E.3.7. Limit of detection
  - E.4. Validating modified components of a test or platform
    - E.4.1. Modified assay conditions, reagents, instruments, and analytical pipelines
    - E.4.2. Added/modified test content
- F. Analytical Standards
  - F.1. Specimen requirements
  - F.2. DNA requirements and processing
  - F.3. Suboptimal samples
  - F.4. Quality control and quality assurance
    - F.4.1. General quality control
    - F.4.2. Bioinformatics
  - F.5. Staff qualifications
  - F.6. Data storage and traceability of patient reports
  - F.7. Reference materials
  - F.8. Proficiency testing
- G. Reporting Standards
  - G.1. Turnaround times
  - G.2. Data interpretation
  - G.3. Reporting of incidental findings
  - G.4. Written report
  - G.5. Data reanalysis
- H. Summary