Diagnostic Sequencing —
Training activity: 4

Details

Select appropriate tools for identifying different types of genomic variation in acquired disease

Type

Developmental training activity (DTA)

Evidence requirements

Evidence the activity has been undertaken by the trainee​.

Reflection on the activity at one or more time points after the event including learning from the activity and/or areas of the trainees practice for development.

An action plan to implement learning and/or to address skills or knowledge gaps identified.

Considerations

• Sample types and quality considerations
• Tumour heterogeneity
• Germline vs somatic
• SNVs, Indels, CNVs and structural variants in acquired disease
• Driver and passenger variants
• Limit of detection
• Quality metrics
• Storage of data in appropriate formats according to local and national standards, taking into consideration patient confidentiality
• Data integrity and patient safety

Reflective practice guidance

The guidance below is provided to support reflection at different time points, providing you with questions to aid you to reflect for this training activity. They are provided for guidance and should not be considered as a mandatory checklist. Trainees should not be expected to provide answers to each of the guidance questions listed.

Before action

• What specific types of genomic variation in acquired diseases (e.g., somatic mutations in cancer) will you be considering? How might the requirements for tools differ when analysing acquired versus inherited genomic variation (e.g., considering variant allele frequencies, mosaicism)? What is your current understanding of the types of genomic variation commonly found in acquired diseases?
• What specific bioinformatics tools used for identifying somatic mutations and other acquired genomic changes do you hope to discover? How will you learn to differentiate between germline and somatic variants using different tools? What challenges do you foresee in selecting tools that can reliably identify low-frequency somatic variants or handle complex genomic rearrangements in acquired diseases?
• Will you investigate bioinformatics pipelines and tools specifically designed for somatic variant calling and analysis? Will you discuss with your training officer the specific contexts of acquired disease (e.g., specific cancer types) you might consider? Are there any key concepts related to acquired genomic variation that you plan to review? What are your initial thoughts on approaching the selection of tools for acquired disease analysis?

In action

• Are you focusing on tools specifically designed for somatic variant calling or considering adapting tools used for inherited disease? What criteria are you prioritising when evaluating tools for acquired disease (e.g., sensitivity for low allele frequency variants)?
• Are you encountering differences in the availability or suitability of tools for acquired versus inherited disease analysis? What challenges are arising related to distinguishing somatic from germline variants? What new knowledge are you gaining about the specific requirements for analysing genomic variation in acquired diseases? How does this selection process relate to your understanding of somatic mutations and cancer genomics?
• If you are struggling to find tools that can reliably identify somatic variants, are you exploring different filtering strategies or considering tools that incorporate paired normal samples? Are you considering if your search terms or focus need to be adjusted based on the specific context of acquired disease you are considering?

On action

• Summarise the key steps you took in selecting tools for identifying different types of genomic variation in acquired disease. What types of tools did you consider, and how did your considerations differ from those for inherited disease? Did you focus on tools specifically designed for somatic variants or consider adapting germline variant callers? What were the main challenges you encountered that were specific to acquired disease variant calling tool selection?
• What new skills or knowledge did you gain regarding the selection of tools for acquired disease variant identification? Were there any unexpected findings regarding the availability or suitability of tools compared to those for inherited diseases? What did you learn from these? How did your reflection-in-action influence your approach to selecting tools for acquired disease? How does this activity connect to your understanding of analysing NGS data in a clinical setting and the specific requirements for acquired disease analysis? Did you enhance your critical awareness of databases and tools relevant to this task?
• What aspects of tool selection for acquired disease require further development? How will you apply this learning to future tasks involving somatic variant identification? What specific actions will you take to consolidate your understanding? For example, will you compare the performance metrics of different somatic variant callers? What resources or support would be beneficial for your continued learning in this area?

Beyond action

• Reflect on your experience of selecting tools for acquired disease variant identification in light of subsequent activities and learning. Have you since worked on training activities involving somatic variant calling or analysis? How did your initial experience with this training activity influence your approach to these later tasks? Have you observed differences or similarities in tool selection for inherited versus acquired disease that you didn’t appreciate initially? As you review the S-BG-S1 module, consider how your reflections on this training activity have evolved. Have new insights emerged regarding the specific challenges of acquired disease variant analysis and the tools available? Have you discussed the selection of tools for acquired disease with colleagues? Did these conversations offer new perspectives or reinforce your initial understanding?
• Recognise the contribution of this training activity to your broader skill set. How has your experience in selecting tools for acquired disease analysis enhanced your ability to critically evaluate bioinformatics resources and understand the nuances of somatic variant detection compared to germline variant detection? In your current work or subsequent training activities, how have you applied the understanding gained from this training activity? Have you become more aware of specific tool requirements or limitations for acquired disease analysis? How has your approach to similar tasks been shaped by this experience?
• Identify the transferable skills developed through this activity. How might your understanding of tool selection for acquired disease, including awareness of somatic-specific challenges, inform your future work in research or clinical service development? What future steps will you take to further develop your expertise in this area? Are there specific types of acquired variation or analysis pipelines you plan to investigate further?

Relevant learning outcomes

#	Outcome
# 2	Outcome Evaluate sources of information about variation in the human genome including access, application and clinical impact.
# 3	Outcome Select appropriate tools for next generation sequencing (NGS) analysis of inherited and acquired disease.