Training activity information
Details
Apply the appropriate analytical strategies for rare disease cases
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.
Considerations
- Filtering strategies e.g., trio analysis, inheritance based/gene agnostic and panel selection/application
- Disease-phenotype association (e.g., Exomiser or OMIM) with appropriate allele frequencies according to ancestral lineage
- National guidance for testing and rationale for selection of testing protocol
- Patient consent – what analyses are ethical
- Communication with the multidisciplinary team
- Risk of incidental findings and the impact on patients
- Storage of data in appropriate formats according to local and national standards, taking into consideration patient confidentiality
- Implications for the patient
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 is the objective of applying the correct analytical strategies specifically for cases involving rare diseases? What specific analytical pipeline or workflow is used for rare diseases in your setting? What are the criteria for prioritising variants? How should family data (if available) be integrated?
- Have you analysed genomic data for rare diseases before, and are you familiar with typical rare disease analysis workflows (e.g., filtering based on frequency, predicted impact, inheritance patterns)? What possible challenges might you face e.g. dealing with novel or extremely rare variants? Interpreting variants of uncertain significance? Integrating complex phenotypic information, or troubleshooting pipeline issues? How might you handle them? When would you need to seek advice on challenging cases, variant interpretation, or pipeline problems? How do you feel about applying analytical strategies for rare disease cases?
- What specific skills do you want to develop e.g. becoming proficient in a specific rare disease analysis pipeline? Improving your ability to filter and prioritise variants effectively? Enhancing your understanding of different inheritance patterns? What specific insights do you hope to gain e.g. the common challenges in rare disease genomics? Understanding how different analytical steps contribute to reaching a diagnosis? Appreciating the importance of integrating clinical information?
- If you’ve worked on rare disease cases before, have you reviewed any notes on challenging aspects or areas for improvement in your analysis approach? What important information do you need to consider before embarking on the activity e.g. ensuring access to the appropriate analytical tools and pipelines? Understanding the specific clinical details for the case and any known genes or regions of interest? Reviewing relevant guidelines or best practices for rare disease analysis?
In action
- As you are applying analytical strategies for a rare disease case, make a note of anything that feels surprising or different from what you anticipate. For example, does a specific variant filtering step produce unexpected results, do you find contradictory evidence for a variant in a known rare disease gene, or does the integration of family data reveal an unexpected inheritance pattern? Consider how this experience compares with previous experiences of similar activities, such as other genomic data analyses or general problem-solving tasks. Does it feel more or less familiar, especially in the context of rare diseases?
- Identify how any unexpected developments, such as an unusual variant or a pipeline error, impact your immediate actions. Do you immediately review the filtering criteria, re-examine the raw data for the variant, or discuss the unexpected finding with your training officer? Do you adapt or change your analytical strategy as a result? For instance, do you decide to use an alternative variant prioritisation method, incorporate additional phenotypic information, or modify your workflow for integrating family data? Do you find it difficult to adapt your analytical approach when faced with complexity or uncertainty? Does it affect your confidence in reaching a diagnosis for the rare disease case? Do you feel positive you can reach a successful conclusion?
- Do you recognise when you might need to seek immediate advice or help, such as when a variant of uncertain significance requires expert clinical interpretation or when a pipeline issue points to a fundamental bioinformatics flaw you cannot resolve? Identify what you learn as a result of the unexpected development. For instance, do you learn a new filtering technique for rare variants, a specific strategy for interpreting challenging inheritance patterns, or a more effective way to integrate clinical and genomic data in rare disease cases?
On action
- Summarise the key steps involved in applying the analytical strategy to the rare disease case. Describe the rare disease case you worked on and the specific analytical strategy you applied. Detail the tools or pipelines you used. Were there any specific events, actions, or interactions that felt important during the analysis, such as unexpected findings or challenges specific to rare disease analysis?
- What specific learning can you take from this rare disease analysis? For example, what strengths did you demonstrate in applying appropriate filtering or using rare disease databases? What skills or knowledge gaps were evident regarding the specific analytical approach or interpreting findings in the context of a rare disease? How did this experience compare against previous times you have analysed rare disease cases (if any)? Were any previous actions for development in this area achieved? Do you feel your practice has improved? Identify any challenges you experienced, such as dealing with case complexity, integrating clinical information or interpreting variants of uncertain significance, and how you reacted to them. Did these challenges affect your ability to deal with the situation? Were you able to overcome them? Was there anything significant about this activity, such as needing to seek advice or clarification on the analytical strategy or interpretation, or ensuring you were working within your scope of practice?
- Identify the specific actions or ‘next steps’ you will take based on this experience to support your learning. What analytical strategies or approaches will you adjust for future rare disease cases? Has anything changed in terms of what you would do if faced with a similar situation again? Do you need to practice specific filtering techniques, using rare disease resources, or integrating clinical data further? How will you assimilate any feedback you received on your analysis?
Beyond action
- Think back on the different rare disease cases you have analysed. Have you revisited your reflections on challenging cases or strategies that did not initially yield clear results? What actions did you previously identify to improve your rare disease analytical strategies, such as refining filtering steps, incorporating specific databases, or improving your understanding of particular inheritance patterns? Have you actively implemented these changes in subsequent analyses? Are you ready to consistently apply a more refined and effective rare disease analytical approach based on your past experiences and learning? Has discussing rare disease cases and analytical challenges with experienced colleagues transformed your perspective on applying these strategies?
- How has analysing multiple rare disease cases developed your ability to select and apply appropriate analytical strategies effectively? Do you feel more adept at troubleshooting or navigating complex cases? How does the cumulative learning from analysing various rare disease cases prepare you for assessments involving variant interpretation in a clinical context, which frequently relate to rare diseases? It also provides insight into the clinical impact, as highlighted by relevant clinical experiences. Based on your practice, are you better at recognising when a rare disease case presents unusual complexities or appears to be outside your current scope of analysis, requiring expert input?
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. |
| # 4 |
Outcome
Analyse NGS data in a clinical setting applying appropriate quality control and data validation. |