Bioinformatics

Question 1

What are the problems with using BLAST to make metabolic networks?

Answer 1

Similar enzymes with close EC numbers but different functions have different functions
Holes/incomplete networks
Paralogs have same sequence but different function in different organisms

Question 2

How is BLAST used to make metabolic networks?

Answer 2

Annotation of gene function based on alignment to existing sequences
Mapped onto KEGG reference network

Question 3

Which proteins can be aligned by BLAST for networks?

Answer 3

Core metabolic processes only

not regulation or signalling

Question 4

How can reliability of BLAST be improved?

Answer 4

Bidirectional BLAST

Question 5

How can distant homologs be detected?

Answer 5

PSI/iterative searches

Hidden Markov Models

Question 6

What proportion of distant homologs are detected by PSI BLAST?

Answer 6

40%

Question 7

What results do Hidden Markov Models give?

Answer 7

Probability of relationship

Question 8

How does BLAST work?

Answer 8

Gives probability sequences have a similarity caused by relationship not S=chance
E values show closeness of relationship

Question 9

What does PRIAM do?

Answer 9

Annotates proteins based on EC number

Question 10

When is PRIAM used?

Answer 10

SharkHunt software annotates raw genome sequence with introns/exons
metaTIGER database combines PRIAM alignments

Question 11

What can metabolic networks be used for?

Answer 11

To find processes unique and essential to parasite that are absent in host/ will not cause large cascade implications

Question 12

How many sequences are included in metaTIGER?

Answer 12

> 100 eukaryotes

>400 prokaryotes

Question 13

What systems make quantitative studies of metabolic networks?

Answer 13

Biomolecular systems
Bipartitie graphs
Flux balance analysis

Question 14

What structure do bimolecular systems have?

Answer 14

Protein vertices
Interaction edges
Can be labelled with names and strength of interaction

Question 15

What are the disadvantages of bimolecular systems?

Answer 15

No direction of signal
Impossible to represent stoichiometry
Multiple cross links make it complicated
Lots of unlinked edges
Common substrates ignored

Question 16

What is the structure of bipartite graphs?

Answer 16

2 sets of vertices for enzymes and metabolites

directional edges labelled with stiochiometry

Question 17

What are matrixes?

Answer 17

A table version of bipartite graphs

Question 18

What are the disadvantages of bipartite graphs?

Answer 18

No proton balancing

Complex lines from common substrates

Question 19

When can Michaelis Menton kinetics be used to study flux?

Answer 19

In small systems such as single reactions

Question 20

What data is needed for Michaelis Menton studies?

Answer 20

Kinetic constants for all reactions

Concentrations of all metabolites

Question 21

What size of system can flux balance analysis be used for?

Answer 21

> 1000 reactions

Question 22

What are the conditions of flux balance analysis?

Answer 22

Steady states must be maintained to measure [outputs] to determine rates of interconversion

Question 23

In complex networks, which pathway is favoured?

Answer 23

The one that promotes most growth

Question 24

What can flux balance analysis be used for?

Answer 24

Assessment of drug targets
Metabolic engineering
Determining effects of varying nutrients