Exam question

Question 1

What is P4 medicine?

Answer 1

• Preventative
• Personalized
• Predictive
• Participatory

Question 2

What is the difference between whole genome sequencing and exome sequencing?

Answer 2

• Whole genome sequencing → sequencing the entire genome.
• Whole exome sequencing → sequencing the protein-encoding regions of the genome (i.e. the exomes).

Question 3

Describe what gene mutation and what disease process is associated with gyrate atrophy.

Answer 3

• OAT mutation
• OAT deficiency → ornithine not converted to GSA/P5C → ornithine accumulation → toxic → impacts retina (e.g. myopia).

Question 4

Why is the eye such a good model to study?

Answer 4

• Easy to use iPSCs to differentiate them into retinal cells.
• For example, you can create a organoid from iPSCs and follow the development of the ‘eye’. From there on, you can also isolate specific retinal cells (e.g. RPE) and perform an MTT assay.

Question 5

Name biological, psychological and contextual factors that influence intellectual disabillity.

Answer 5

• Biological → type of mutation, comorbidity, side effects medication, age, enzyme/protein expression, loss of heterozygosity/epigenetic mechanisms/modifying genes/metabolic factors.
• Psychological → stress, traumatic events, attachment issues, anxiety, coping style, acceptance
• Contextual → family, living situation, SES, level of education, health care system, culture, diet/physical activity/lifestyle

Question 6

What is important to do when describing someone’s dysmorphic features?

Question 7

What statistical analysis to do to accomplish 0.1 (???)?

Answer 7

(I think) Doing multiple N=1 trials and doing a meta-analysis based on these multiple N=1 trials.

Question 8

What are the two most important neurotransmitters in the E/I ratio?

Answer 8

• Glutamate
• GABA

Question 9

Why use glibenclamide for Cantu patients?

Answer 9

Glibenclamide is a CI- importer blocker. It increases the fE/I ratio by reducing inhibition and enhancing excitation. It has been shown to increase the fE/I ratio and to reduce Cantu symptoms.

Question 10

Why include rare metabolic disease in newborn screening?
OR
What are the requirements to include rare disease in newborn screening?

Answer 10

• So that you can create a database with all patients with the rare disease/know which patients have the rare disease
• So that you can prevent early-life complications

Question 11

Why is it hard to research rare diseases?

Answer 11

• Little known about natural history of disease
• Disease is rare, so few patients
• Low statistical power/evidence levels
• Heterogeneity in disease
• Lack of approval and reimbursement

Question 12

Sometimes it is hard to distinguish patient and controls cells in cultrue. How can this still be done with cultured cells?

Answer 12

• Use (bio)markers that are specific for disease or for healthy patient.
• Use DNA sequencing (e.g. whole genome sequencing) to identify the patient and control cell culture.

Question 13

What is deep phenotyping and name 3/4 ways this can be done.

Answer 13

• The precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described.
• Genome sequencing, imaging techniques, use AI, identifying symtoms associated with disease.
• Standards are required to link heterogeneous clinical data from different sources including clinical records, project databases, and public repositories

Question 14

What is the phenotype…?

Answer 14

The observable traits of an organism

Question 15

Describe the workflow of CAS compared to a conventional workflow.

Answer 15

• Conventional workflow → diagnostics → surgery → evaluation
• CAS workflow → diagnostics → advanced diagnostics → virtual surgical planning → surgery and intraoperative feedback → evaluation

Question 16

What is the advantage of 3D sterophotogrammetry?

Answer 16

• No radiation dose
• Provides digital archive of the patient’s face without exposure to radiation

Question 17

Name the 4 steps for a CAS approach.

Answer 17

• (advanced) Diagnostics
• Virtual surgical planning
• Surgery and intraoperative feedback
• Evaluation

Question 18

In which situations do you want to use a cone beam CT instead of the 3D stereophotogrammetry?

Answer 18

• Cone beam CT is used to produce 3D images of your teeth, soft tissues, nerve pathways and bone in a single scan.
• 3d stereophotogrammetry is used to map the whole face or the feature-rich areas around the nose and eyes

Question 19

How do you know if there is enough evidence to implement a biomarker into the clinical guidelines?

Answer 19

If the use of the biomarker is justified (the way the biomarker should be used is proven). Or: the biomarker has proven analytical validity -> implies that the test for the tumor biomarker is accurate and reliable in the type of specimen to which it will be applied

Question 20

Why would you want to make a (standard operating procedure) SOP for pre-analytical variation and why does the SOP needs to contain global feasibility?

Answer 20

By making a SOP for pre-analytical variation, you can create stanards of how a sample should be handled pre-analytically. This minimizes the chances of pre-analytical variation. The SOP needs to contain global feasbility, to determine whether and to what degree the practice of pre-analysis differs globally and how feasible it is to get everyone to work according to the SOP.

Question 21

What are the advantages and disadvantages of simoa compared to ELISA?

Answer 21

Advantages: high sensitivity, automated
Disadvantages: more sample volume needed, specialized training, number of proteins analyzed with simoa is low, costly.

Question 22

50 MS patients and 30 control. On these participants, a protein study is performed where protein Z is identified. Is this sufficient to use protein Z as a biomarker? If not, what would you do differently?

Question 23

What is the difference between analytical and clinical validation? And why is analytical validation necessary?

Answer 23

• Analytical validation: proving that the way the assay works (the method) is acceptable/reliable to identify the concept of interest.
• Clinical validation: proving that the assay used is able to identify the concept of interest.
• Analytical validation ensures that you know to what degree the assay is reliable to measure the biomarker.

Question 24

Which groups would you include if you were to research a AD biomarker?

Answer 24

Control and AD, but also other neurodegenerative diseases (parkinsons, LBD, etc.) to ensure that the biomarker to be found is specific for AD disease proces.

Question 25

Absolute values of biomarkers are not always valuable, while they could say something about the disease process and mechanism. Why is a biomarker not always useful/informative?

Answer 25

Not disease specific, strongly rises with age, associated with other processes (comorbidities) for example, normalization.

Question 26

A question about which biomarkers (NfL, tTau and AB42) can be used for AD.

Question 27

What disease process is reflected by biomarkers NfL, tTau and AB42?

Answer 27

• NfL -> degeneration of axons in MS
• tTau -> synaptic dysfunction (tau detachtment from axonal microtubuli)
• AB42 -> faulted clearance or overproduction of ab42 causes aggregation of faulty ab42.