2 - Genomic Data Analysis

Question 1

What is shotgun sequencing?

Answer 1

DNA is randomly fragmented, sequenced, then assembled computationally

Question 2

What is average coverage (two definitions)?

Answer 2

Total nucleotides ÷ genome size

Average number of reads covering each genome position

Question 3

What is position-specific coverage?

Answer 3

Number of reads covering a particular base

Question 4

What challenges affect genome assembly?

Answer 4

Sequencing errors → mismatches

Ploidy effects → diploid organisms have differing maternal/paternal alleles

Repeats (~50% of human genome) collapse when reads are too short

Question 5

How can repeat regions be resolved in sequencing

Answer 5

Use longer reads to anchor repeats in unique context

“Walk in” from both sides of repeats until sequences overlap

Question 6

What is N50?

Answer 6

The length of the shortest contig such that 50% of the genome is contained in contigs of that length or longer

Question 7

What does a higher N50 indicate?

Answer 7

Better assembly continuity

Question 8

What are structural variants?

Answer 8

Large-scale changes in genome structure such as insertions, deletions, duplications, translocations, or inversions

Question 9

What is a synonymous mutation?

Answer 9

Mutation that does not change the amino acid

Question 10

What is a non-synonymous mutation?

Answer 10

Mutation that changes the amino acid and is more likely to affect phenotype

Question 11

What are non-coding mutations?

Answer 11

Mutations in promoters, enhancers, or operators that affect regulation

Question 12

What is a common method to detect and prioritise mutations?

Answer 12

Multiple sequence alignments

Question 13

What does Hardy-Weinberg equilibrium state?

Answer 13

Allele and genotype frequencies remain constant unless evolution acts

Question 14

What conditions are required for Hardy-Weinberg equilibrium?

Answer 14

No mutations
No migration
Random mating
Large population
No natural selection

Question 15

What is the equation for allele frequencies?

Answer 15

p + q = 1

Question 16

What is the equation for genotype frequencies?

Answer 16

p² + 2pq + q² = 1

Question 17

What do the genotype terms represent?

Answer 17

p² = homozygous dominant
2pq = heterozygous
q² = homozygous recessive

Question 18

What is the purpose of enrichment analysis?

Answer 18

To identify pathways/functions that are overrepresented in a gene list compared to background

Question 19

What databases are used in enrichment analysis?

Answer 19

GO (Gene Ontology) and KEGG (curated pathways)

Question 20

Name tools used for enrichment analysis

Answer 20

g:Profiler
DAVID
GSEA
ShinyGO

Question 21

What is conserved synteny?

Answer 21

Preservation of gene order between species

Question 22

What is whole-genome phylogenetics used for?

Answer 22

Comparing complete genomes to reveal phenotypic, metabolic, or evolutionary differences

Question 23

What does incongruence in genomic history mean?

Answer 23

Different genes in the same genome may have different evolutionary histories (e.g. horizontal gene transfer)

Question 24

What is a pangenome?

Answer 24

The total genetic content of a species

Question 25

What is the core genome?

Answer 25

Genes shared by all individuals

Question 26

What is the accessory genome?

Answer 26

Genes present in some but not all individuals

Question 27

Why is pangenome analysis important?

Answer 27

It helps study diversity, adaptation, and functional potential

Question 28

What is machine learning increasingly used for in genomics?

Answer 28

Variant effect prediction, gene function prediction, genome annotation, and pattern recognition in big data

Question 29

Why is machine learning useful in genomics?

Answer 29

It can detect patterns difficult to identify with classical statistical methods.

Question 30

What is a contig?

Answer 30

A contiguous stretch of DNA sequence assembled from multiple overlapping DNA fragments