Training activity information
Details
Analyse and interpret the results of NGS sequencing for a panel of genes related to paediatric disorders
Type
Entrustable training activity (ETA)
Evidence requirements
Evidence the activity has been undertaken by the trainee repeatedly, consistently, and effectively over time, in a range of situations. This may include occasions where the trainee has not successfully achieved the outcome of the activity themselves. For example, because it was not appropriate to undertake the task in the circumstances or the trainees recognised their own limitations and sought help or advice to ensure the activity reached an appropriate conclusion.
Reflection at multiple timepoints on the trainee learning journey for this activity.
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 does success look like?
- Identify what is expected of you in relation to analysing and interpreting data from NGS gene panels for paediatric disorders.
- Consider how the learning outcomes apply, specifically considering the interpretation of genomic variants using bioinformatic tools and interpreting / reporting genomic testing with recommendations.
- What does accurate analysis and interpretation of NGS panel results look like, contributing to diagnosing paediatric patients with rare inherited disorders?
- Discuss with your training officer to gain clarity on expectations for interpreting and reporting NGS panel data.
What is your prior experience of this activity?
- Think about what you already know about analysing and interpreting NGS sequencing data, particularly for gene panels.
- Consider possible challenges you might face during the activity, such as interpreting novel variants, VUS, or complex inheritance patterns, and think about how you might plan to handle them.
- Recognise the scope of your own practice for this activity e. know when you will need to seek advice or help with analysis and interpretation of results of NGS sequencing for a panel of genes related to paediatric disorders.
- Acknowledge how you feel about embarking on this analysis and interpretation.
What do you anticipate you will learn from the experience?
- Consider the specific skills you want to develop related to analysing and interpreting NGS panel data, classifying sequence variants, and using bioinformatic tools.
- Identify specific insights you hope to gain regarding the process of reviewing and prioritising variants from NGS panels and correlating them with the paediatric patient’s phenotype.
What additional considerations do you need to make?
- Consult actions identified following previous experiences of analysis and interpretation of results of NGS sequencing.
- Identify important information you need to consider before embarking on the activity, such as the principles of NGS sequencing and the typical workflow for gene panel analysis. You should also review established guidelines and best practices for classifying sequence variants, the bioinformatic tools used, and essential clinical information needed for accurate interpretation in paediatric patients.
In action
Is anything unexpected occurring?
- Are you noticing anything surprising or different from what you anticipate during the analysis and interpretation of the NGS sequencing panel results?
- Are you encountering situations such as:
- Identifying an unexpected or difficult-to-interpret variant (e.g., VUS or a deep intronic change) that requires immediate review of raw alignment data or consultation of multiple external resources?
- Technical limitations of the assay (e.g., low coverage in a critical region) being encountered, affecting the quality of the variant calls and complicating the interpretation?
- You are struggling to filter or prioritise variants because the clinical information provided is too limited to confidently assess their relevance to the paediatric patient’s phenotype?
How are you reacting to the unexpected development?
- How is this impacting your actions? For example, are you responding to the situation appropriately? Are you adapting or changing your approach to filtering variants?
- Consider the steps you are taking in the moment, such as:
- Immediately reviewing the raw sequencing data or consulting internal/external databases to verify the quality and potential impact of a complex variant?
- Seeking immediate advice from a senior colleague or clinical scientist regarding the classification of a challenging variant or a complex case?
- Are you ensuring that your analysis and interpretation considers the limitations of the gene panel and the overall quality of the NGS data?
- How are you feeling in that moment? For instance, are you finding it difficult to adapt to the technical limitations or the nuances of variant classification for paediatric disorders? Is it affecting your ability to prioritize variants relevant to the patient’s condition?
What is the conclusion or outcome?
- Identify how you are working within your scope of practice. For example, are you successfully classifying the variant based on best practice guidelines, or needing support because the variant is novel and requires external expertise for classification?
- What are you learning as a result of the unexpected development? For example, are you learning a specific filtering strategy for handling high volumes of variants of uncertain significance (VUS), or gaining key insight into assessing the quality of NGS data based on coverage metrics?
On action
What happened?
- Begin by summarising the key points of the experience of analysing and interpreting NGS sequencing results for a paediatric gene panel.
- Consider specific events, actions, or interactions which felt important, such as identifying point mutations or small indels, applying bioinformatics tools, or correlating variant findings with clinical phenotype.
- Include any ‘reflect-in-action’ moments where you had to adapt to the situation as it unfolded, for instance, immediately reviewing raw alignment data for a difficult-to-interpret variant or adjusting variant filtering parameters based on limited clinical information. How did you feel during this experience?
How has this experience contributed to your developing practice?
- Identify what learning you can take from this experience regarding the application of NGS panels and how the interpretation of results informs patient diagnosis and management.
- What strengths did you demonstrate e.g., proficiency in variant filtering? What skills and/or knowledge gaps were evident e.g., difficulty using specific bioinformatic tools or classifying complex or novel variants?
- Compare this experience against previous sequencing analysis activities – were any previous identified actions for development achieved? Has your practice in NGS analysis and interpretation improved?
- Identify any challenges you experienced e.g., technical limitations of the assay or struggling with variant classification guidelines and how you reacted to these. Did this affect your ability to deal with the situation? Were you able to overcome the challenges?
- Identify anything significant about the activity, such as needing to seek advice or clarification on variant pathogenicity or bioinformatics pipeline issues or needing to escalate to ensure that you were working within your scope of practice.
- Acknowledge any changes in your own feelings in analysing and interpreting such results.
What will you take from the experience moving forward?
- Identify the actions or ‘next steps’ you will now take to support the assimilation of what you have learnt, including from any feedback you have received regarding your ability to analyse and interpret results from NGS sequencing.
- What will you do differently next time you analyse and interpret NGS panel data? Has anything changed in terms of what you would do if you were faced with a similar situation again?
- Do you need to practise any aspect of the activity further, such as undertaking additional training in NGS data analysis or acquiring further knowledge about specific genes or bioinformatics approaches relevant to paediatric NGS panels?
Beyond action
Have you revisited the experiences?
- Have you reviewed your actions from your previous reflections for this activity? What specific actions did you previously identify you would need to take to improve your practice related to interpreting genomic variants and reporting results?
- Have you completed these previously identified actions? For example, if you planned to review bioinformatics for the processing of large datasets, how did completing this action impact your ability to filter or prioritise variants from a complex NGS panel?
- Engage in professional storytelling with peers, near peers, or colleagues about NGS variant classification. Have discussions with colleagues or learning about bioinformatics for large datasets improved your ability to analyse and interpret variants of uncertain significance (VUS) since the original experience?
How have these experiences impacted upon current practice?
- Consider how the accumulated learning from performing or reflecting on NGS analysis will support you in preparing for observed ‘in-person’ assessments for the module, such as a DOPS titled ‘Classify a variant’.
- How has your practice related to analysis and interpretation developed and evolved over time? For example, how do you apply the skills learned in analysing and interpreting NGS panel results when working with other sequencing data or complex genetic findings in your current practice?
- What are your identified actions for continued development of your NGS data analysis and interpretation skills, and how will this foundational understanding prepare you to interpret and report on increasingly complex datasets e.g., transition to whole exome/genome sequencing?
Relevant learning outcomes
| # | Outcome |
|---|---|
| # 4 |
Outcome
Interpret genomic variants, including copy number changes, and investigate the clinical significance of variants using bioinformatic tools using best practice guidelines. |
| # 5 |
Outcome
Interpret and report genomic testing relevant to paediatric conditions, including appropriate recommendations for patient management. |