Role of proteomics and bioinformatics in target validation MCQs With Answer

Role of proteomics and bioinformatics in target validation MCQs With Answer

This set of MCQs is designed for M.Pharm students studying Principles of Drug Discovery and focuses on how proteomics and bioinformatics contribute to target validation. Questions cover experimental proteomics techniques (mass spectrometry, labeling strategies, targeted MS), data analysis concepts (peptide identification, FDR, quantification methods), post-translational modifications, proteogenomics, and computational tools for functional annotation, network analysis, structural modeling and pathway enrichment. Each question emphasizes practical interpretation of results and common pitfalls in biomarker and target validation workflows. Use these MCQs to test comprehension, apply theoretical knowledge to experimental design, and prepare for research or exams in translational drug discovery.

Q1. What is the primary role of proteomics in target validation during early drug discovery?

• Predicting drug metabolism based solely on mRNA expression
• Identifying and quantifying proteins and their modifications to confirm target relevance
• Replacing all biochemical assays with in silico simulations
• Measuring only total protein concentration without functional context

Correct Answer: Identifying and quantifying proteins and their modifications to confirm target relevance

Q2. Which experimental platform is most commonly used for large-scale protein identification and characterization in target validation?

• Flow cytometry
• LC-MS/MS (liquid chromatography coupled to tandem mass spectrometry)
• Next-generation DNA sequencing
• Enzyme-linked immunosorbent assay (ELISA)

Correct Answer: LC-MS/MS (liquid chromatography coupled to tandem mass spectrometry)

Q3. Which of the following labeling methods are examples of isobaric tags used for multiplexed quantitative proteomics?

• SILAC and label-free
• iTRAQ and TMT
• SRM and PRM
• 2D-PAGE and DIGE

Correct Answer: iTRAQ and TMT

Q4. For targeted validation of candidate protein biomarkers identified by discovery proteomics, which mass spectrometry approach is best suited?

• Top-down MS of intact proteins only
• Shotgun LC-MS/MS without targeted acquisition
• Selected/Multiple Reaction Monitoring (SRM/MRM) or Parallel Reaction Monitoring (PRM)
• Matrix-assisted laser desorption ionization imaging (MALDI-MSI)

Correct Answer: Selected/Multiple Reaction Monitoring (SRM/MRM) or Parallel Reaction Monitoring (PRM)

Q5. In proteomics data analysis, what is a commonly accepted peptide-spectrum match (PSM) false discovery rate (FDR) cutoff for high-confidence identifications?

• 50%
• 20%
• 5%
• 1%

Correct Answer: 1%

Q6. Which post-translational modification (PTM) is often critical in signaling and is commonly interrogated during target validation studies?

• Acetylation of DNA bases
• Phosphorylation of serine/threonine/tyrosine residues
• Ubiquitin-independent cleavage of RNA
• Lipidation of mRNA

Correct Answer: Phosphorylation of serine/threonine/tyrosine residues

Q7. What is proteogenomics?

• Using proteomics to study plant genomes only
• Integration of proteomic and genomic/transcriptomic data to improve gene annotation and identify novel protein isoforms
• Sequencing of proteins instead of DNA
• A method to quantify metabolites using protein markers

Correct Answer: Integration of proteomic and genomic/transcriptomic data to improve gene annotation and identify novel protein isoforms

Q8. Which bioinformatics resource is primarily used to explore predicted and experimental protein–protein interactions for target prioritization?

• BLAST
• STRING
• ClustalW
• PubChem

Correct Answer: STRING

Q9. What is the purpose of Gene Ontology (GO) enrichment analysis in proteomics-driven target validation?

• To directly measure protein concentrations
• To determine which biological processes, molecular functions, or cellular components are overrepresented among a set of proteins
• To sequence unknown proteins
• To design primers for PCR

Correct Answer: To determine which biological processes, molecular functions, or cellular components are overrepresented among a set of proteins

Q10. When a protein’s experimental 3D structure is not available, which computational method helps predict its tertiary structure to aid target validation and docking studies?

• Homology (comparative) modeling
• RNA-Seq assembly
• Chromatography
• Flow cytometry clustering

Correct Answer: Homology (comparative) modeling

Q11. Which label-free quantitative proteomics metric is considered semi-quantitative and is based on the count of identified spectra per protein?

• Isobaric labeling ratio
• Spectral counting
• Absolute quantification using AQUA peptides
• Western blot densitometry

Correct Answer: Spectral counting

Q12. The human plasma proteome displays an extremely wide dynamic range in protein concentrations. Approximately how many orders of magnitude does this dynamic range span?

• 2 orders of magnitude
• 5 orders of magnitude
• 10 orders of magnitude
• 20 orders of magnitude

Correct Answer: 10 orders of magnitude

Q13. What distinguishes top-down proteomics from bottom-up proteomics in the context of target validation?

• Top-down digests proteins into peptides; bottom-up analyzes intact proteins
• Top-down analyzes intact proteins including PTM patterns; bottom-up analyzes proteolytic peptides derived from proteins
• Top-down uses genomic data only; bottom-up uses metabolomics
• They are identical approaches with different names

Correct Answer: Top-down analyzes intact proteins including PTM patterns; bottom-up analyzes proteolytic peptides derived from proteins

Q14. In biomarker validation, which ROC (receiver operating characteristic) area under the curve (AUC) value is generally interpreted as indicating excellent diagnostic performance?

• AUC = 0.5
• AUC = 0.7
• AUC = 0.8
• AUC ≥ 0.9

Correct Answer: AUC ≥ 0.9

Q15. Which comprehensive curated database is widely used for protein sequence information, functional annotation, and cross-references useful in target validation?

• GenBank
• UniProt
• KEGG Pathway only
• ChEMBL

Correct Answer: UniProt

Q16. In mass spectrometry-based proteomics, what is a peptide-spectrum match (PSM)?

• A predicted protein structure matched to a homology model
• The alignment between a measured MS/MS spectrum and a peptide sequence from a database
• A match between two different protein interaction networks
• The correspondence of a metabolite peak to a protein

Correct Answer: The alignment between a measured MS/MS spectrum and a peptide sequence from a database

Q17. Why is cross-validation used in bioinformatics models applied to proteomics data for target selection?

• To increase the number of features in the model
• To assess and improve the predictive performance and avoid overfitting
• To perform experimental digestion of proteins
• To visualize protein bands on gels

Correct Answer: To assess and improve the predictive performance and avoid overfitting

Q18. How can molecular docking contribute to target validation workflows when combined with proteomics evidence?

• By automatically validating clinical trial outcomes
• By predicting likely ligand binding poses and relative affinities to support hypothesized target–ligand interactions
• By replacing the need for experimental affinity measurements entirely
• By sequencing the target protein

Correct Answer: By predicting likely ligand binding poses and relative affinities to support hypothesized target–ligand interactions

Q19. Which multiple testing correction method is commonly applied during pathway or GO enrichment analysis to control the false discovery rate?

• Bonferroni correction only
• Benjamini–Hochberg procedure
• No correction is typically needed
• Fisher’s exact test without adjustment

Correct Answer: Benjamini–Hochberg procedure

Q20. What is a key advantage of integrating proteomics with bioinformatics during the target validation stage?

• It eliminates the need for any experimental follow-up
• It enables prioritization of targets by combining quantitative protein evidence with pathway, network and structural context, reducing false positives
• It guarantees a successful drug candidate will be found
• It limits analysis to only highly abundant proteins

Correct Answer: It enables prioritization of targets by combining quantitative protein evidence with pathway, network and structural context, reducing false positives

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